PATIENT COMPLIANCE - PharmXpert Academy

ForewordQuality healthcare outcomes depend upon patients’adherence to recommended treatment regimens. Patientnon-adherence can be a pervasive threat to health andwellbeing and can carry an appreciable economic burdenas well. In some disease conditions, more than 40% ofpatients sustain significant risks by misunderstanding,forgetting, or ignoring healthcare advice. While no singleintervention strategy can improve the adherence of all patients, decades ofresearch studies agree that successful attempts to improve patient adherencedepend upon a set of key factors. These include realistic assessment of patients’knowledge and understanding of the regimen, clear and effective communicationbetween health professionals and their patients, and the nurturance of trust inthe therapeutic relationship. Patients must be given the opportunity to tell thestory of their unique illness experiences. Knowing the patient as a person allowsthe health professional to understand elements that are crucial to the patient’sadherence: beliefs, attitudes, subjective norms, cultural context, social supports,and emotional health challenges, particularly depression. Physician-patientpartnerships are essential when choosing amongst various therapeutic optionsto maximise adherence. Mutual collaboration fosters greater patient satisfaction,reduces the risks of non-adherence, and improves patients’ healthcare outcomes.For most medical conditions, correct diagnosis and effective medical treatmentare essential to a patient’s survival and quality of life. A significant barrierto effective medical treatment, however, is the patient’s failure to follow therecommendations of his or her physician or other healthcare provider. Patient nonadherence(sometimes called non-compliance) can take many forms; the advicegiven to patients by their healthcare professionals to cure or control disease istoo often misunderstood, carried out incorrectly, forgotten, or even completelyignored. Non-adherence carries a huge economic burden.Journal for Patient Compliance gives you these specific step-by-step, practicalguidelines to achieve better adherence levels.We bring you another array of very interesting articles. Carole North, co-founderand Joint Managing Director of 90TEN Healthcare, looks into a differentapproach to changing health behaviour. Dr Anna Baker of Atlantis Healthcare hasa closer look at motivational interviewing, and Michael Wong, the founder of thePhysician-Patient Alliance for Health & Safety (PPAHS) argues that, the next timeyou start to think about an adherence programme, take a page from smokingcessation – make sure it listens to patients and responds to their individual needsin improving medication adherence. This patient-centric approach should be apart of each and every strategic decision.In the Regulatory section, Kathrin Heinritz of Pharmexx GmbH looks into theimpact of selected legal factors on pan-European patient-centric programmes.In the Behaviour section, Charles Clark and his team look into a linguistic approachto improving self-care and compliance, and Zoe Tziakou and ConstantinaGeorgaki of PCC HELLAS discuss whether an all-in-one personal point-of-care is adream or reality.I hope you all enjoy this issue of JPC, and I wish you all a Very Merry Christmasand a wonderful New Year.See you all in 2013.Mark A. BarkerEditorial Advisory BoardAndree Bates, Managing Director, EularisAnna Dirksen, Senior Manager, PSI Behavior ChangeChris Penfold, Vice Chairman - East Midlands PackagingSociety, Consultant, Freelance Packaging SpecialistCarole North, Managing Director, 90 TEN HealthcareDyan Bryson, Managing Partner/VP Patient Strategy& Outcomes for Inspired Health StrategiesElisabeth Moench, President & CEO of Medici GlobalHelen Lawn, Managing Director, Helen Lawn & Associatesa healthcare PR and communications agencyIsabelle Moulon, Head of Medical InformationSector, European Medicines AgencyJay H. Bolling, President and CEO,Roska Healthcare AdvertisingJoseph Bedford, Director of MarketingAlmac Clinical TechnologiesLaura Bix, Assoc. Prof. School of PackagingMichigan State UniversityLouis A. Morris, Ph.D., is President of LouisA. Morris and Associates, IncMark Duman, Managing Director ,MD Healthcare ConsultantsMichael Wong is Managing Director at hcCatalystPeter van Iperen, Experienced Pharmaceutical ProfessionalPhill Marley, Packaging Account Manager,Global Quality Operations AstraZenecaRonald E. Weishaar, Executive Director, ObservationalResearch, PharmaNet Development GroupSaurabh Jain, Director of Patient ValueServices and CME Solutions at Indegene.Steve Kemp, Business Development Director at BreconPharmaceuticals and Chairman of HCPC EuropeTassilo Korab, Co-founder of HCPC Europe(Healthcare Packaging Council)Vassilis Triantopoulos, CEO of BIOAXIS HealthcareWalter Berghahn, Executive Director, TheHealthcare Compliance Packaging Council6 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Think Tankpregnancy by March 2010, and 61% of YP surveyed saidthey would discuss the campaign’s safe sex message withfriends, or visit a GP or sexual health service provider forcontraception and STI advice.These are just a few examples of where the Nudge theorywas successfully incorporated into healthcare campaignsto change the health behaviour of a specific segment of acommunity. Crucially, the approach should be targeted ratherthan blanket; a core part of the initial Nudge-informed socialmarketing process is not only to define types of behaviour butalso identify potential advocates to help promote change. Theprinciple can be incorporated into adherence programmes, toboth standardise anticipated levels of acceptable medicationadherence among healthcare professionals, and to placegreater responsibility on, and thereby empower, the patient.Social marketing is the application of marketing principlesin campaigns that seek to achieve social change. It is used toadvance a social cause, idea or behavioural change. There aresome key principles involved in the use of social marketing;namely, that it:• Targets specific groups of people• Utilises research to build effective strategies• Segments audiences within those target groups and thentailors strategies to their needs, wants, resources andbehavioursEngland and Wales have some of the highest rates of teenagepregnancy in Western Europe. In 2010, 90TEN Healthcarewas commissioned to encourage young people (YP) to usecontraception and attend local sexual health service centers,with the aim of reducing teenage pregnancy by 5% across a12-month period.Extensive consultations were undertaken with all thestakeholders involved (including young people and staffdirectly engaging with them at local sexual health servicesand pharmacists, and through youth engagement teams).This consultation process not only provided the necessaryresearch outcomes to inform our strategy, but also fullyengaged some stakeholder champions, which included alarge group of young people who felt empowered and had asense of ownership in the campaign.The campaign resulted in an 11% reduction in teenReferences1. Cialdini RB, Reno RR and Kallgren CA (1990). A focus theoryof normative conduct: Recycling the concept of norms toreduce littering in public places. Journal of Personality andSocial Psychology 58(6): 1015–1026.2. Earp BD, Dill B, Harris JL, Ackerman JM & Bargh JA (2012).No sign of quitting: Incidental exposure to no-smoking signsironically boosts cigarette-approach tendencies in smokers.http://www.yale.edu/acmelab/articles/Earpetal2012JAPS.pdf3. The Guardian. http://www.guardianpublic.co.uk/nudgetheory-can-effect-behaviour-change-but-care-is-needed4. Applying behavioural insights to reduce fraud, error and debt.The Cabinet Office. http://www.cabinetoffice.gov.uk/sites/default/files/resources/BIT_FraudErrorDebt_accessible.pdf5. GP Online. http://www.gponline.com/Medeconomics/article/1092121/reducing-missed-appointments/Carole North is co-founder and JointManaging Director of 90TEN Healthcare.She has over 11 years’ experiencedelivering programmes that increaseadherence to treatment by empoweringpatients to change their health beliefsand behaviours, supporting HCPsto manage those patients, and developing initiatives thathelp reduce acute hospital admissions. 90TEN Healthcareconsistently wins awards for its adherence, concordance, andexperiential and social marketing campaigns, and is currentlydelivering patient adherence programmes in 23 countries.Email: carole.north@90ten.co.ukwww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 9

Watch PagesHelping Patients Take Their Medication:Lessons from Helping Patients Quit SmokingSmokers are not patients -- or, at least, that’s the view thatmost people have of smokers. Like most “self-inflicted” healthrisks, like drinking too much alcohol and sharing needles, thestigma attached to smoking and smokers is pervasive 1 .Unfortunately, not treating smokers as “patients” andseeing smoking as a “disease” can lead us to not applyvaluable lessons from quit smoking programmes to helppatients take their medication.The interesting thing about smoking cessation is that weas a society often treat this as a social problem. For example,to get dad to quit, we solicit the help of his family (wife, kids,and friends). We suggest aids that may help, like exercise anddiet. We recommend that he see his doctor and try nicotinereplacement therapy. Surrounding the patient with thenecessary support that he needs to quit (and not what wewant) is critical.With that in mind, I, together with the VietnameseAmerican Cancer Foundation (VACF) and GlaxoSmithKline(GSK) developed a programme directed towards theVietnamese American community, targeting “Little Saigon”in Orange County, California. Little Saigon has the largestnumber of Vietnamese outside of Vietnam. Unfortunately,this community was facing a number of enormous challenges.It had one of the US market’s highest smoking rates (36 percent) 2 and had therefore been deeply impacted by the scarsof this addiction – death, disease and their consequenceson family wellbeing and livelihood. Moreover, entrenchedcultural and social acceptance of smoking made it an evenmore difficult task, with smoking for example still occurringin restaurants and offices with social impunity.We purposely engaged the entire community in theprogramme (doctors, a community patient advocate, anda pharmaceutical company). Local doctors were asked toactively speak with their smoking patients about the need toquit. As Dr Loc D. Bui (a Little Saigon doctor) urged his fellowcolleagues at the start of the campaign, “As physicians,we know the danger of smoking. I would like to see all thephysicians in our community talk to their patients aboutsmoking and strongly encourage them to quit.”The pharmaceutical GSK, although a manufacturer ofnicotine replacement products, was content to fund theseactivities without active product promotion. For example, ina survey of local physicians, doctors’ attitudes and beliefsabout nicotine replacement therapies involving gums,patches and lozenges were explored along with “cold turkey”,herbal supplements, diet, exercise, or anything else theymight recommend to their patients.These patients were made aware of the cadre of healthcareexperts, quit lines, and volunteers at the VACF that stoodready to assist them. “People don’t realise that it is notjust their health, it is the health and welfare of their wholefamily that the smoker puts at risk,” said Leonard Tran (thenExecutive Director of VACF). “Men who develop smokingrelateddiseases often leave their families without means forsupport. By quitting smoking, men can give themselves theirbest chance of being able to be there for their families in thelong term.”The community responded to VACF’s message. A youngwidow, for example, spoke on community radio to tell herheart-wrenching story of not getting her husband to quitsoon enough. Sadly, he had recently died, leaving his wifeand kids to deal with bills and payments, and continuing tolive their lives without him.The results? Activity on the quit lines and at VACFincreased dramatically. As one doctor observed, epitomisingthe programme results, “Since the programme started, I havehad 4-5 patients per month quit smoking which is 4-5 timesmore than I usually have.”However, what the programme had really done ismotivational counselling at its best -- doctors intervened asthe medical authority, the community provided stories andemotional support, and the local cancer foundation (VACF)12 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Watch Pagesosteoporosis researchers concluded, “In this randomisedcontrolled trial, we did not find a statistically significantimprovement in adherence to an osteoporosis medicationregimen using a telephonic motivational interviewingintervention.”Unfortunately, the results of studies like these may resultin programmes like these never starting. As Dr Jon Ebbert(Professor of Medicine at Mayo Clinic) emailed us:Tragically, this may mean that stakeholders may notpay attention to what may be a very promising andinnovative strategy to improve medication adherence.Behavioural strategies have been used very successfullyin getting patients to quit smoking and can be agreat tool in getting patients to take their physicianprescribedmedication.So, the next time you start to think about an adherenceprogramme, take a page from smoking cessation – make sureit listens to patients and responds to their individual needs inimproving medication adherence.This patient-centric approach should be a part of each andevery strategic decision.Why? Because the old marketing adage that the customeris always right applies even to the healthcare industry. Don’tdiscount such things as complaints of side-effects, lifestyleinconveniences, and forgetfulness -- listening and respondingmay be the difference between an adherent patient and anon-adherent patient.gave individualised and group counselling and advice.More importantly, we applied techniques that we knewwould work. We were not encumbered with the need anddesire to wait for clinical trial data, or have confirmed anddocumented returns on investments from other smokingcessation programmes before starting the Little Saigonprogramme.Waiting for this data before acting is truly regrettable.Recently, for example, the Archives of Internal Medicinereported on the results of a study to examine whether atelephone-based counselling programme rooted inmotivational interviewing would improve adherence toosteoporosis medication.For this study, more than 1000 Medicare patients who hadbeen newly prescribed osteoporosis medication were dividedinto a control group, who were mailed educational materials,and an intervention group, who received telephone-basedcounselling.Median medication adherence was 49% in the telephonegroup and 41% in the control group. In short, as theReferences1. Jennifer Stuber et al., “Smoking and the emergenceof a stigmatized social status” Social Science andMedicine (May 2008) http://deepblue.lib.umich.edu/bitstream/2027.42/60953/1/stuber_smoking%20and%20stigma_2008.pdf (accessed April 8, 2012).2. A Provider’s Handbook on Culturally Competent Care,Smoking Among Asian Americans: A National TobaccoSurveyMichael Wong is the founder of thePhysician-Patient Alliance for Health &Safety (PPAHS). PPAHS is an advocacygroup devoted to improving patienthealth and safety; and is composedof physicians, patient advocates, andprofessional healthcare organizations,and can be found at www.ppahs.org Like a serial entrepreneur,Mike has been behind many healthcare initiatives, includingencouraging people to quit smoking, get tested and treatedfor hepatitis, and take their medications as prescribed by theirphysicians. As well, he has helped improve access to healthcare.Email: mwong@ppahs.orgwww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 13

Regulatory & Market PlaceThe Impact of Selected Legal Factors onPan-European Patient-centric ProgrammesA comparison between four European countriesWhilst today there exists a common understanding inthe pharmaceutical industry and amongst payors thatnon-adherence poses a tremendous problem, and numerousprogrammes to overcome this challenge have been developedand implemented, Pan-European approaches to increasepatient adherence are still rare.One reason for the rarity of Pan-European patient-centricprogrammes could be that these programmes are still decidedby the country affiliate of a pharmaceutical company andnot centrally, with the role of paying for such a Pan-Europeanservice residing with the pharmaceutical industry and not thepayors.Does the pharmaceutical industry still see patientcentricservices as a component of local commercialisation(nationally driven) initiatives and not a core marketing(centrally driven) activity? Should a pharmaceutical companylet individual countries decide on what is appropriate, or isthe decision due to the fact that marked differences betweencountries in terms of legal issues, healthcare markets or otherfactors like technological development and cultural variationsare present?Due to the targeted scope of the article, we shall focusin this paper on the differences between countries in thearea of legal issues whilst acknowledging that there mightbe other factors impacting the decentralism of patientcentricservices, too. The evaluation of the legal differencesrepresents an assessment of the current frameworks basedon an analysis carried out in the countries observed in thisarticle. We acknowledge that there is permanent change inthis field and as such the situation may change rapidly insome countries. It is therefore indispensable to verify thecurrent legal framework in each market for each specificproject! The author has written this article to the best of herknowledge and on availability per country but does not takeany liability for the legal statements made.Four different European countries, including aScandinavian (Denmark), a middle European (Germany),a Western European (Belgium) and a Southern Europeancountry (Spain) have been chosen to compare.If we consider health management services in this article,the definition “nursing service” (nurse or other adequateHCP visits the patient at home to inform, educate, train andsupport the patient) and “medical dialogue centre” (nurseor other adequate HCP calls the patient to inform, educate,train and support) shall apply. These services are directlytargeted at patients in order to increase adherence – and arenot classical homecare services.In order to evaluate the legal framework for patient-centricservices and their implementation, four important steps havebeen analysed according to the set-up of a patient-centricprogramme: first of all, the question if a patient-centricservice per se is a promotion by the pharmaceutical companyto the patient; second, how the patient can actually beaccessed; third, if we need any consent of the patient in orderto implement the patient programme with him or her; andlast but not least, what actually can be done by a nurse (sinceit is assumed in this article that usually these are nurses) atthe patient’s home.Is a Patient-centric Service Including a Nurse at thePatient’s Home or a Medical Dialogue Centre per se aPromotion of the Product to the Patient?Contrary to the US, we can anticipate that in none of thefour European countries selected is any kind of promotionallowed from pharmaceutical company to patients for Rxproducts or in general for Rx products to patients. The legalframework in the countries is similar since it is based on anEU directive 1 . In Germany, for example, it is stated: “Pharmacompanies are not allowed to promote Rx-products directlyto patients / consumers”, “Pharma companies are not allowedto pro-actively and directly contact patients for productrelatedinformational purposes” or “Pharma companies arenot allowed to pro-actively and directly contact patients forfurther support with the product”.Similar statements can be found in the three othercountries 2 .However, the Spanish and Danish laws foresee aclause where “Pharma companies are allowed to prepareinformational materials, that the doctor may provide to apatient, regarding Rx-products which, due to the complexityof their dosage, route of administration, etc., require theprovision of additional information”, provided that:• This information is only intended to improve compliancewith treatment.• The material does not include promotional informationon the product.In Belgium, for example, it is similarly not considered as apromotion if they do not contain any product promotion and/ or answer a specific question about a particular product:“correspondence, possibly accompanied by material ofa non-promotional nature, needed to answer a specificquestion about a particular medicinal product” and “factual,informative announcements and reference material relating,for example, to pack changes, adverse-reaction warnings aspart of general drug precautions, trade catalogues and pricelists, provided they include no product claims 3 .”Already in this statement, it can be concluded that materialaimed at improving compliance without any promotionalcontent can be used in order to support the patient – can thatbe viewed in the same way for a nurse who visits a patient,or might a medical dialogue centre call not be seen as apromotion, but rather as the trial supporting the patient?If we consider that the usual procedure of a patient-14 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Regulatory & Market Placecentric service in reality foresees that the patient is onlyinformed about the patient-centric service after a producthas been prescribed by a physician, the promotional senseof this service is already negated in the first place. It must,however, be ensured that the nurse or HCP is well trained tonot “promote” the product at the patient’s home in any way.Graph: possible way of approaching the patient for a patient-centric programmeIn order to NOT trespass on the promotional factor thatthe information on the programme could have, it is thereforeadvisable to use the pharmaceutical company’s own salesforce, or that of a third party, to inform the physicians and/ or pharmacists about the programme, who then in turninform the patients after prescription of the product.Concluding that no promotional support of the drug ispossible as the patient-centric programme only starts whenthe patient is already on the drug following the prescriptionof the physician, the ways in which the patient can beaccessed shall now be analysed.We have already seen that patients can be informed bythe treating physician about a patient-centric programme ifthe product has already been prescribed to the patient andthe information is non-promotional as regards the product.However, is there any supporting way to access the patientfor a programme? There seem to be alternative ways!In Germany, Denmark and Belgium, for example, packageinserts as regards the programme, and also flyers or brochuresat the physician and / or at the pharmacy, can be used inorder to inform about the patient-centric programme (onlyafter the product has been prescribed).Moreover, the pharmacist could also be used in order totransfer the message of the patient-centric programme tothe patient. In Spain, the optimal and legal way to approachthe patients would also be via the physicians, and nonpromotionalmaterials can be used as discussed above.If the Patient can Successfully be Approached and isHappy to Join the programme, the Question of PatientConsent comes into PlayIn all of the four countries, the patient has to provide consent! 4Except for Denmark, in the three other countries, contact withthe patient has to be in writing. It should also be possible toexpress consent via registration on a homepage.In Denmark, even if it is not mandatory to receive theconsent in writing, it is definitely recommended to do so inorder to avoid any doubt.According to Article 5 of Organic Law 15/1999 in Spain, thepatient whose personal data are collected must previously beinformed, in an express, precise and unmistakable way, of thefollowing matters:• Of the existence of a personal data filing system or theprocessing of personal data, of the purposes of thecollection of the personal data, and of the recipients of theinformation;• Of the mandatory or optional character of his or herresponse to the questions asked;• Of the consequences of the collection of the data or of therefusal to provide the data;• Of the possibility to exercise at any time the rights ofaccess, rectification, cancellation and opposition;• Of the identity and address of the processor, or, if applicable,of its representative.In Denmark, with the consent of the patient, healthcarepersonnel can pass on information about the patient health,private information, or other confidential information toother healthcare personnel. Moreover, physicians who aretreating a patient are then, in the case of a patient-centricprogramme, allowed to obtain information about a patient’shealth, private information or other confidential informationfrom electronic systems when it is necessary in connection toan ongoing treatment of the patient from the HMS nurse 5 .In Germany and Belgium, moreover, there has to be writtenconsent by the patient to store and process his/her data. Thepatient data has to be separated from the pharmaceuticalentrepreneur. The staff involved in the project have to beinstructed about data protection 6 .Under no circumstances should the reporting to thepharmaceutical manufacturer, or a third party involved inthe programme, include any personal data or any medicalpersonal data, but only anonymous data.Which Tasks can be Performed at Home for Patients by anHCP in the Framework of a Health Management Service?After having passed the three challenges prior to the beginningof the programme, it is indispensable to know what tasks andinterventions can be performed with the patient at home bya nurse (we assume that it is a nurse who visits the patient athome. If it is another HCP, the facts might be different).In Germany, for example, nurses are allowed to informthe patient at home about the disease, treatment and theapplication of a product as well as to show the patient howto use the product; they are not allowed to set infusionsor injections themselves at home of a patient due to theregulations of the BÄK (Bundesärztekammer = Federalmedical council) – a physician would have to be withinearshot 7 . As outlined in point number one, they are notallowed to promote the product in any way, but only toneutrally discuss it and its usage.It has to be taken into account, however, that in Spain, forinjections and infusions, the home-setting scenario can onlybe fulfilled if the use of the product has not been restrictedto the premises of the hospital. If this is the case, the nurse isallowed to carry out injections and infusions.In all of the countries, no other HCP (except an alternativepractitioner for OTC drugs in Germany) other than a physiciancan carry out injections into the patient on own responsibility.16 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Regulatory & Market PlaceInjections and Infusions on Own ResponsibilityInjections and Infusions by Physician’s DelegationGraphs: overview on which HCP is allowed to administer injections onown responsibility and by delegation 8However, if we look at injections by “delegation” ofa physician, nurses in all countries are able to do this – inDenmark even pharmacists. Nevertheless, what has to beconsidered is the fact that the “delegation” in the differentcountries is differently defined. In Germany, for example, thephysician has to be within earshot, but this is not applicableto a patient at home.For infusions, the same applies as for injections. Onlyphysicians can administer them on their own responsibilitywhile infusions by delegation can be carried out by nurses(taking into account the “within earshot” rule in Germanyand regulations in the other countries).The situation is different for information provided topatients about indication and therapy. This is possible inall four countries by not only physicians, but also nursesand pharmacists at the patient’s home and via the medicaldialogue centre, and forms one of the core foundations ofhealth management services. In Germany, the regulationdefines that it is possible if it is supportive of the physician’stherapy or to fulfill the manufacturer’s safety duties.Informing Patients about Indication and TherapyAnother core factor is the support of patients in the safeapplication of the drug, which is possible to do on ownresponsibility by physicians and nurses and with pharmacists(except Belgium).Support of Patients in the Safe Application of the Drug 9Set-up of Pan-European Health Management ServicesHaving analysed the four countries in terms of four differentlegal challenges to overcome when setting up a patientcentricprogramme, it can be concluded that it is basicallypossible for pharmaceutical companies and third partyproviders to carry out the health management servicesdescribed in the European countries discussed.In general, it seems to be advisable to go with a third-partyprovider, since resources, structures and processes might bemissing and also time-consuming to set up within the strictpatient data protection laws in the European countries. It willmake it easier for the pharmaceutical industry to pass thischallenge to a third-party provider. Moreover, there may bescepticism towards a pharmaceutical company interactingdirectly with a patient, even if for supporting reasons.In Spain, pharmaceutical companies can’t access any patientinformation regarding the diagnosis and/or treatmentdefined by the physician. So, a third-party model is not anoption, it’s a must to implement such patient programmes.The legal differences are not so severe that it is impossibleto carry out one or other of the services discussed. It is justintricacies that have to be taken care of, and other factorsthat might play a role in the set-up of a patient-centricprogramme need to be carefully managed.Pharmaceutical headquarters could, after having taken onboard the legal analysis, issue minimum requests with regardto the patient-centric programme. This might concern thecontent of the programme, the process of the programmeand possible cooperation partners, the recruitment ofadequate HCPs, IT systems, and the KPIs that are importantfor the set up and smooth running of the project.It is recommended that then the countries evaluatethe minimum requirements with the legal and healthcaremarket situation in the country as regards their feasibility,www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 17

Behaviour ProgrammesA Linguistic Approach to ImprovingSelf-care and ComplianceIn the adherence literature, over 200 variables have beenexamined to determine their association with patientadherence to self-care behaviours 1-3 . Previous approacheshave had either little predictive power or were dependenton epidemiologic variables that were not amenable tointervention. Ideally an adherence questionnaire should besimple to administer and provide a reliable classificationthat predicts individual adherence and generates actionableinformation. Herein we provide evidence that the CoMacDescriptor, based upon linguistic analyses of patientstatements regarding their disease, meets these criteria.Main body Paragraphs:Over the past several years, an interdisciplinary researchgroup at Indiana University, consisting of linguists andhealthcare professionals, has identified linguistic indicatorsin three domains related to adherence: control orientation,based on locus of control research 4 ; agency, based on selfefficacy5 ; and affect or attitude and emotion 6 . Based uponthis linguistic research 7-10 and using the language thatreveals a subject’s worldviews on each of the domains, wehave developed a questionnaire, the CoMac Descriptor.The CoMac Descriptor relies on patient’s self-identificationwith the actual words used by other patients with the sameworldview. The instrument categorises patients into one ofeight bins: internal or external control orientation, high orlow agency, and positive or negative affect (Table 1). Thequestionnaire can be administered in 10 to 15 minutes. Thedata presented below describe the research that led to thedevelopment of the CoMac Descriptor. Data are providedto show that the Descriptor can reliably predict self-carebehaviour compliance in persons with type 2 diabetes andhypertension.Table 1: Descripter TM ClustersRecognising the importance of understanding the patient,the interdisciplinary research group at Indiana Universityconducted in-depth interviews of 43 English-speakingsubjects with type 2 diabetes. They were analysed by domainby two to four coders into one of the eight bins (internaland external control, high and low agency and negativeemotions). The linguistic feature systems (word use, sentencestructure, and other expressions) for agency and controldomains were generated using grounded theory analysis thathas been extensively used in qualitative analyses of healthcommunication. The linguistic features of affect expressionsthat were tested in this sample of diabetes patients camefrom a well-established linguistic theory of affect appraisal 6 .The initial CoMac Descriptor, based upon the results ofthese analyses, was a 35-item survey. Its validity was testedin 20 persons with diabetes as compared to the in-depthinterviews of the same persons. The CoMac Descriptorresponses and interviews were analysed independently fromeach other. The results from the CoMac Descriptor codingwere compared to those of the interview coding to determinethe concurrence of the domain placement of the interviewsversus the CoMac Descriptor. In this administration of the35-item version, there was 75% agreement between CoMacDescriptor results and the linguistic analysis of individualinterviews; the agreements between the CoMac Descriptorand control orientation, agency, and affect were 75%, 70%,and 80%, respectively. There was also 100% agreementon content validity arrived at through inter-rater reliabilityassessment by three content specialists in linguistics and testdevelopment.After dropping the questions below r=0.7, the CoMacDescriptor was revised to a 28-item survey. The resultant28-item CoMac Descriptor was administered in a similarstudy to 16 new subjects. There was a 74% agreementbetween CoMac Descriptor results and individual interviewlinguistic analysis as well as 100% agreement on contentvalidity arrived at through inter-rater reliability assessmentby content specialists in linguistics and test development.Thus, our initial testing demonstrated that a briefquestionnaire yielded reliable information in three domainsknown to explain compliance in over 70 per cent of thesubjects tested. We concluded that such a questionnaireis useful for individualising the educational approach toinitiating or improving self-care adherence behaviours.For example, persons in the most favourable domains(internal control, high agency and positive emotion) wouldreceive positive reinforcement to continue their successfulbehaviours. For persons in the least favourable domains(external control, low agency and negative emotions)extensive intervention would be necessary beginning withanalysis of the specific negative emotion (e.g. fear, anxiety,depression, etc.). Each of the eight placements would generateactionable approaches most likely to be consistent with theindividual’s control orientation, agency and emotion.Control orientation is a strong perception and the leastlikely of the three domains to be mutable. Nevertheless,the terms the clinician would use in approaching personswith internal or external control orientation would be quitedifferent. For those individuals with an external controlorientation, the clinician would couch his or her advice interms of “Your provider holds the key to your health” or “9 outof 10 persons with diabetes have benefited from taking thismedication.” In contrast, internal control oriented individualswould receive advice beginning with such statements as“You are in the driver’s seat” or “Consider the benefits of thismedication -- you may find out that it addresses your healthconcerns.”20 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Behaviour ProgrammesFor an individual, neither agency nor emotion levels areimmutable. Yet, there are a number of studies that reportnegative emotions, especially depression and anxiety, to becommon in chronic disease and lead to low levels of patientcompliance with self-care behaviours. Therefore, our approachto patients with negative emotions could take priority overagency until the negative emotions have been addressed.After addressing emotion, the healthcare professional canbegin to address low agency; that is, infrequently engagingin self-care behaviours. The healthcare professional canapproach persons with internal control, but low agency, bysuggesting that they decide on their own what small stepsthey would take to increase self-care behaviours. For thosewith low agency and external control, the approach wouldbe for the healthcare provider to suggest a specific smallstep toward enhancing the ability and confidence of theindividual with each step.Our next step in the development of the CoMacDescriptor was to compare the results generated by theCoMac Descriptor with the impressions of a clinicianactively engaged in the care of the patients being studied.In order to accomplish this we engaged the collaborationof a nurse practitioner caring for the patients with type2 diabetes in our validation studies. She had extensiveexperience with these individuals and knowledge of theirself-care behaviours. We familiarised the nurse practitionerwith the domains being studied and how she might recognisethem. Of the 16 patients with diabetes, there was completeconcordance between the nurse practitioner’s classificationof the patients and that derived from the CoMac Descriptorin all but three cases. Of the three in which there was notconcordance, one did not complete the questionnaire and onewas clearly gaming the questionnaire. This study, therefore,assured us that we were dealing with a questionnaire thatyielded clinically meaningful and actionable information. Ournext developmental step addressed the generalisability ofthe linguistic approach that we had developed. Specifically:would a modification of the CoMac Descriptor directedat hypertension yield comparable results to those seen indiabetes and would such a modification for hypertension ina different culture or language yield comparable results tothose seen with the questionnaire in English?To address these questions we administered a modifiedCoMac Descriptor focused on self-care behaviours inhypertension to over 358 persons with hypertension inEnglish, Spanish, German, and Italian. We then comparedresults to a widely used questionnaire to predict compliance,the MARS-5. Our a priori hypotheses were that those subjectswho were internally oriented, and had high agency andpositive emotions would be the most compliant, and thatthose who were externally oriented, and had low agencyand negative emotions would be the least compliant. Thedata generated in this study supported these hypotheses 11 .Further, we were able to detect differences in the clusteringresults obtained in different populations with different nativelanguages. While we will need further study to characterisecompletely intercultural and inter-linguistic issues in ourapproach, we believe the data generated thus far support ourcontention that a linguistic approach to predicting self-carebehaviours is both reliable and generalisable.We believe that our linguistic approach yields informationthat both predicts self-care behaviour and provides avenuesor approaches to improve self-care behaviours when suchimprovement is necessary. First let us begin with twoquestions: “Does the CoMac Descriptor yield informationthat predicts compliance to self-care behaviour as well ascurrent questionnaires?” and “Does the CoMac Descriptoryield information that is more useful and actionable thanthat provided by current questionnaires?” Table 2 summarisesthe most common variables used to predict adherence toself-care behaviours. They are demographic and medical/epidemiological in nature.Table 2: Conventional explanatory variables and descriptive statisticsAge, mean = 52, S.D. = 12Demographic variables• Employed: 54%• Any college education: 48%• Stopped medicine because I got better: 11%Medical variables• Cost of the medication: 6%• Avoiding side effects: 10%• Had severe side effects: 8%• Medication not effective: 2%Data provided by Quintiles/MediGuardWhile demographic and medical information is interesting,it is not really useful to the clinician as the variables are notmutable. Table 3 shows the significant variables generatedfrom the study discussed in the previous paragraph. Whilethey give the clinician direction on how he or she mightchange the regimen, if that seems clinically appropriate,they are not particularly useful in developing an educationalapproach for the individual patient. The table also showsthat the significant variables predicted somewhat over 65%of the variation.Table 3: Results for all demographic and medical variablesCorrectly classified into an adherence category: 65.24%Significant variables• Had severe side effects• Avoiding side effects• Employed• Stopped medicine because I got betterData provided by Quintiles/MediGuardTable 4 summarises the results from the CoMac Descriptorin the same study. Predictability of compliance was slightlybetter than for the demographic and medical variables. Moreimportantly, as discussed above, the information providesuseful information that the healthcare provider can use in hisor her approach to the patient.Table 4: Results for the linguistic clusters in predicting adherenceCorrectly classified when using only linguistic variables: 66.86%Correctly classified when using all medical, demographic and linguisticvariables: 70.37%Data provided by Quintiles/MediGuardWe conclude that patients see the world differently andthose differences are important both in predicting behaviourand in changing it. For addressing adherence, knowing howpatients think is more important than their demographicsor attitudes toward their medical regimen. The CoMacwww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 21

Behaviour ProgrammesDescriptor provides information on how the patient thinksthat is useful to the clinician in the development of aneducational approach to improve self-care behaviour andeventually outcomes. We summarise our conclusions inTable 5.Table 5: CoMac ConclusionsPatients perceive the world differentlyFor addressing adherence, knowing how patients think is more valuable thanknowing their demographics and their concerns about medicineThe CoMac Descriptor provides what you need to approach the individualpatient in a tailored patient-centric manner that is consistent with theirworldviewsReferences1. Morris LS, Schulz RM. Patient compliance—An overview. JClin Pharm Ther. 1992; 17: 283-295.2. Vermeire E, Hearnshaw H, Van Royen P, Denekens J. Patientadherence to treatment: Three decades of research. Acomprehensive review. J Clin Pharm Ther. 2001; 26: 331-342.3. van Dulmen S, Sluijs E, van Dijk L, de Ridder D, Heerdink R,Bensing J, et al. Furthering patient adherence: A positionpaper of the international expert forum on patientadherence based on an internet forum discussion. BMCHealth Serv Res, 2008; 8(1): 474. Wallston KA, Wallston BA, DeVellis R. Development of themultidimensional health locus of control (MHLC) scales.Health Educ Behav. 1978; 6: 160-170.5. Bandura A. Self-efficacy: Toward a unifying theory ofbehavioral change. Psychol Rev. 1977; 84: 191-215.6. Martin JR, White PRR. The language of evaluation: Appraisalin English. New York: Palgrave Macmillan; 2005.7. Connor U, Lauten K. (invited submission). A multi-methodanalysis of diabetes patients’ health beliefs and actions.In: Hamilton H, Chou WS, eds. Handbook of Language andHealth Communication. New York: Routledge.8. Lauten K, Connor U, Antón M, Balunda S, Goering E, HayatA, Roach P. (2010, November). “You are what you talk”– patient-centered interactions. Paper presented at theICADE Diabetes Conference 2010, Indianapolis, IN.9. Lauten K, Connor U, Antón M, Balunda S, Goering E, HayatA, Roach P. Patient-centered adherence improvement. Paperpresented at: International Conference on Communicationin Healthcare; 2010 September; Verona, Italy.10. Connor U, Cortes V. A Corpus linguistic analysis of diabetespatients’ health beliefs and action. Paper presentedat: American Association of Applied Linguistics (AAAL)Conference; 2010 March; Atlanta, GA.11. Sandy R, Clark C, Connor U, Lauten K, Mac Neill R.Determinants of adherence: a comparison of commonlyused variables to linguistically identified worldviews.Presented at: Patient Adherence, Communication andEngagement USA 2011 Conference; 2011 October;Philadelphia, PA.Charles M. Clark Jr., M.D.; ProfessorEmeritus of Medicine Indiana UniversitySchool of Medicine. Dr Clark is formerDirector of the Diabetes Researchand Training Center; Associate Deanfor Continuing Medical Education atIndiana University and Editor in Chiefof Diabetes Care. He has published extensively on facilitatingpatient education and compliance. He is the Medical Directorof CoMac. Email: chclark@iupui.eduUlla Connor, Ph.D.; Chancellor’sProfessor of English, Zimmer EndowedChair in Intercultural Communication,and Director of the Indiana Center forIntercultural Communication at IndianaUniversity School of Liberal Arts. DrConnor has 30 years of experience in thesociolinguistic and ethnographic analysis of communication,most recently applied to patient-centric adherence throughcommunication strategies based on the patient perspective.The author of more than 100 publications, including 10books, Dr Connor has lectured globally about interculturalcommunication and applied linguistics. She is the ChiefScientific Officer of CoMac. Email: uconnor@iupui.eduKathryn Lauten, PhD; AssociateDirector, Indiana Center for InterculturalCommunication at Indiana UniversitySchool of Liberal Arts Principal, CoMacAnalytics, Inc. Kathryn Lauten is aspecialist in health literacy and modelsof health behaviour. Her current researchinvolves combining her background in education, linguisticsand intercultural communication with her work in healthcommunication in order to improve patient outcomes. Shereceived her BA from Dartmouth College and her PhD from theUniversity of Michigan.Email: kathrynlauten@comacanalytics.comRobert Mac Neill Jr., MBA; CEO, CoMacAnalytics, Inc. Mr Mac Neill has morethan 30 years of progressive experiencein the pharmaceutical and health serviceindustries, including roles at Eli Lilly &Co. and Areks, Inc. Mr Mac Neill earneda BA at Brown University and an MBA atHarvard University. Email: macmacneill@gmail.comRobert Sandy PhD; Principal, CoMacAnalytics, Inc. is chief statistician atCoMac Analytics, Inc. He has authoredtwo books and 16 journal articles, andbeen the principal investigator of anNIH-funded study of childhood obesity.His research focus is occupational safetyand health, e.g., the consequences of workplace illnesses.Email: icjz100@iupui.edu22 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Behaviour Programmeswww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 23

Behaviour ProgrammesAn All-in-One Personal Point-of-Care:Dream or Reality?Behavioural change, and treatment plan adherence inparticular, is a multi-faceted phenomenon that requires anequally diverse and constant process of intervention, thatmust be adapted to the individual needs of each patient.Based on this approach, a personal point-of-care can becomea useful tool in strengthening the therapeutic physicianpatientalliance, aiming above all to provide optimalhealthcare services and improve patients’ quality of life.Targeting adherence effectively is a daunting task.Drawing from studies that examine the success of adherenceinterventions, it has been found that multi-faceted interventionsare the most effective 1,2 .The idea behind a promising patient compliance programmemust be based on an approach to patient adherence that isboth holistic and tailored to individual needs, that is groundedin the principles of behavioural change theory and the useof interactive technology. It aims to be an efficient meansof providing information, education, reminders, monitoring,communication, evaluation and support, along with thepatient’s and the physician’s active participation in the processof adhering to a care plan and managing a disease.Tailoring a programme to each patient’s individual needsis the most encouraging form of intervention. Evaluation is animportant means of defining the patient’s unique, individualcharacteristics. The main attributes that should be consideredwhen tailoring a programme to a patient’s needs are presentedhere (Table 1):Educating the PatientOne of the basic factors involved in adherence and, by extension,a programme that aims at reinforcing adherence is keeping thepatient informed on his or her disease and treatment. The taskspatients need to undertake in managing their illness are oftencomplicated and can be difficult to perform consistently. Asmany as 50% of patients do not know what they are supposedto do to take care of themselves after their visit to the doctor’soffice 3 .A point-of-care solution should provide up-to-dateinformation regarding the disease (causes, symptoms andclinical signs, management of its psychosocial impact) andthe treatment (nature, duration, side-effects, management ofside-effects etc). Providing information to the patient createsa sense of security and confidence in better managing his orher condition, and helps the patient meet his or her goals moreeasily.Anastasia, 60: “I enjoyed going through the educationalmaterial on my disease. There were a lot of things I had neverheard about before. After I read it, I called my friends to read ittogether.”At the same time, such a solution should provide detailedinstructions on the proper use of treatment, thus ensuring thatthe medication is safely and appropriately used, with a focus onboosting patient self-confidence and independence. Specifically,patient training can lead to lower risk of drug misuse due tomultipharmacy, and fewer adverse reactions, drug interactionsand health complications.Danae, 39: “I was given the chance to train myself onadministering the drug and now I can help my mother-in-lawwith her medication. This way, it takes less effort and less time,and I can always rest assured that we follow her treatmentplan according to the doctor’s instructions. We used to visit herdoctor every time she had an injection scheduled - commutingwas difficult for both of us.”Patient RemindersReminders for medication-taking and a timely scheduling ofprescribing and obtaining medication are essential and practicalways of facilitating and motivating the patient’s adherence toa treatment plan. An ideal personal point-of-care provides allnecessary reminders, while personalised reminders are able tocover every need of the patient’s everyday schedule.Medication reminders can be interactive, since they requireconfirmation from the patient that the treatment was followed.This way, patient behaviour is recorded with every scheduleddose.Helen, 32: “I don’t have to struggle to remember the datesthat I have to take my medicine. PCC HELLAS provides remindersfor the next scheduled injection. That’s a great help for me,because I tend to forget, it’s my condition that makes me reallyforgetful.”Evaluation of one of our company’s patient adherence plans24 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Behaviour Programmes– which includes, among other things, sending reminders in theform of text messages and requests for call-back confirmationfrom patients after medication-taking – has shown that themajority of patients had a positive opinion of the programme’sinteractive nature. The call-back confirmation as a meansof monitoring the adherence programme was considered apositive feature by the majority of patients and was seen as aform of communication and collaboration between themselvesand our service. It must be noted that none of the patientsconsidered the calls they had to perform as a tiresome or dullprocess. Some patients evaluated this feature as their own“giving back”, a sort of “contribution” to the services offered bythe programme, while others saw it as an extra motivation tomaintain adherence.Based on the above results, it is obvious that when it comesto a programme built on respect for the patient and his or herneeds, on open communication, trust and the provision ofsatisfactory services, the presence of interactivity and activeinvolvement is highly beneficial. Instead of patients acting aspassive spectators, they are being asked to take up an activerole in their treatment. Patient engagement is increasinglyrecognised as a key component of treatment. We believe that itwould be interesting to further investigate the role of interactiveparticipation in adherence programmes, how it interrelates withother factors, and how this interrelation affects adherence.Analysing and EvaluatingThe features of a well-designed personal point-of-care allowfor an initial evaluation of the patient’s state (e.g. throughquestionnaires) and a regular evaluation of the patient’sprogress (through regular follow-up interviews and/orquestionnaires). On top of that, it is possible to further analyseand statistically process this data in order to extract useful anddefinite conclusions concerning the treating physicians and themedical community in general or healthcare providers (nationalorganisations for healthcare) and pharmaceutical controlservices (EMEA etc.).It is also possible to create assessment questionnaires onthe patient’s clinical status and progress through treatment. Inthe hands of healthcare professionals, these questionnaires canbecome valuable tools for appraising the course of the diseaseand treatment. Since time restrictions rarely allow for thecollection and practical application of this data, the physicianis now given the ability to receive such important information,save it for later use and then statistically process it throughintegrated applications. Patients are no longer required to fillin time-consuming questionnaires and assessment forms at thedoctor’s office; online completion provides a major workloadrelief for the healthcare professional.People Behind the Adherence PlanAside from making good use of all technology has to offer, itis necessary for the design, implementation and evaluation ofmulti-component, patient-centred adherence programmes toenjoy the support of a dedicated, inter-disciplinary support teamconsisting of highly-trained personnel. Expertise in behaviouralscience, interpersonal communication and motivationalinterviewing is necessary in order to deploy appropriatebehavioural strategies and enhance intrinsic motivation thataffects adherence.A 2006 study observed HIV patients using a tablet PC-basedcounselling tool designed to support medication adherenceand secondary HIV prevention. The study’s findings suggestthat such a tool may reduce social bias and embarrassment,and encourage patients answering honestly. Nevertheless,participants identified important qualities that a computercannot provide, such as empathy, compassion, and caring 4 .The study results stress that a computer-based solution canbe a valuable solution when coupled with skilled healthcareproviders.Better CommunicationWhat a personal point-of-care effectively does is communicateinformation regarding the patient’s behaviour within his orher treatment plan to the physician or any other healthcareprofessional. Constant monitoring of the patient’s behaviourprovides the physician with a flexible system that allows forevaluation, guidance, and both timely and direct interventionin the patient’s treatment plan. At the same time, it gives usthe ability to identify the patient’s needs and match all actiontaken within the adherence programme to those needs.Adam, 42: “Lying to your doctor is lying to yourself.”Using a personal point-of-care takes advantage of directcommunication technology capabilities (video or voice calls),reinforcing collaboration and the therapeutic physician-patientrelationship. This results in creating optimal conditions for amore effective and meaningful communicative exchange.Feeling IncludedTaking things a step further, patients can be connected withthe patient community and kept up-to-date by receivingrelevant health news, information about their doctor’s practiceand updates on an ongoing basis. Patient groups, healthorganisations and even pharma corporate communications canbe brought into this concept; this sort of interaction can benefitpatients considerably.Anastasia, 60: “I received a news bulletin about the WorldArthritis Day. I was moved; there’s actually an observancededicated to patients like me!”Real-world DataSince September 2012, we have been running a pilot projectwhere patients receive a personal point-of-care, which is actuallya tablet PC that includes all of the previously-discussed features.Participating patients were chosen by their treating doctors andthey will be keeping their tablet until the end of the project, in afew months from now.Participants include both male and female patients of avarying age range: 50% are people aged 31-40, 17% are peopleaged 41-50 and 33% are people aged over 60. In order to betterunderstand the expectations and the impact a compliance toolof this sort can carry, we have designed questionnaires that arebeing given to patients and doctors within a specific timeframe.Most of the patients involved in the pilot project stated thatthey feel well-informed about their medication and their illness;83% of participants said that they know exactly how theirmedication helps them battle their illness and 66% feel thatthey are fully educated about their illness.In the beginning of the project, however, all participantsstated that they expect a personal point-of-care to provide much-www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 25

Behaviour Programmesneeded information on disease and medication. Moreover, overthe course of the pilot project we have been noticing that manypatients frequently ask for additional educational and trainingmaterials. Some of them also said that they often share theeducational content with their friends and family.All patients said that they receive information concerningtheir disease and drugs from their doctor. Roughly 80% ofparticipants also look up relevant information on the internet,while a small percentage obtains information from books,leaflets and/or other patients suffering from the same disease.According to research, doctors overestimate the amount ofinformation they provide to their patients and underestimatethe amount of information patients actually want 5 . Duringdoctor’s visits, a mean of 49 seconds was spent discussing allaspects of newly-prescribed medications 6 .Our findings highlight how crucial the doctor’s role can be ineducating his or her patients. By extension, a personal point-ofcarethat contains educational materials can lead to a decreasein the doctor’s office workload and eliminate the possibilitythat paatients forget or misunderstand a specific piece ofinformation. Most importantly, these materials are selected andapproved by the treating doctor; no more hearsay and dubiousinformation of questionable value.Some findings on patient beliefs are contradictory as well. Thepatients believe that their doctor chose them to participate in theproject based on their familiarity with technology and their positivepre-existing personal relationship. On the other hand, when thedoctors were asked what their criteria were for registering a patientfor the pilot project, the answers we received were quite different.The doctors chose each participant based mostly on his or herhealth condition, low compliance rates and age.Regarding the medication reminder system, 50% of patientsstated that they use mobile phone reminders (mostly patientsaged between 30 and 50). 33% said that they use no remindersand just rely on memory, while 16% use a printed calendar.About 85% of patients expect that a personal point-of-carewill significantly help in reminding them when to take theirmedication.Apart from obtaining information and receiving reminders,some other expectations the patients had are presented inTable 2:Doctors have more or less similar expectations, but believethat such a personal point-of- care will help them in retrievingand analysing important data as well. According to our findings,patients were worried mostly about the progression of theirdisease and their therapy’s outcome. A high number of patientsalso stated that they have to take too many drugs.Roughly 80% of the patients have no contact at all withpatient groups and related health organisations. Underlyingreasons vary. What a personal point-of-care could do is bridgethe gap between patients and associated groups via a constantflow of information and messages (e.g. announcements,newsletters, bulletins).A statement coming from one of the patients vividly sumsup his experience of using his personal point-of-care: “We havebecome inseparable”.Changing LivesIn the words of Heraclitus, it is in changing that we find purpose.Very often people avoid change because they do not know howto go about it; a well-designed personal point-of-care can showthem the way. As we move forward, technology becomes moreand more involved in our lives, resulting in the emergence ofnew needs and new ideas. A personal point-of-care will enablehealthcare providers to render better patient managementand pass crucial messages to their patients in order to achievebehaviour changes. Employing the right approach, the rightpeople and the right tools, we will be there to effectively coverthose needs.References1. McDonald HP, Garg AX and Haynes RB. Interventions to enhance patient adherenceto medication prescriptions: scientific review. JAMA. 2002;288:2868–79.2. Haynes RB, Ackloo E, Sahota N, McDonald HP and Yao X. Interventions forenhancing medication adherence. Cochrane Database Syst Rev. 2008 Apr 16:CD000011.3. Heisler M, Bouknight R, Hayward R, Smith D and Kerr E. The Relative Importanceof Physician Communication, Participatory Decision Making, and PatientUnderstanding in Diabetes Self-management. J Gen Intern Med. 2002 April;17(4): 243–252.4. Skeels M, Kurth A, Clausen M, Severynen A, and Garcia-Smith H. CARE+ UserStudy: Usability and Attitudes Towards a Tablet PC Computer Counseling Tool forHIV+ Men and Women. AMIA Annu Symp Proc. 2006; 2006: 729–733.5. Street RL Jr. Information-giving in medical consultations: the influence ofpatients’ communicative styles and personal characteristics. Soc Sci Med. 1991;32(5):541-8.6. Tarn DM, Paterniti DA, Kravitz RL, Heritage J, Liu H, Kim S, Wenger NS. How muchtime does it take to prescribe a new medication? Patient Educ Couns. 2008 Aug;72(2):311-9. Epub 2008 Apr 11.Zoe Tziakou, Operations Manager, PCCHELLAS. Zoe has been dealing with patientadherence management problems andsolutions on a daily basis. She has beenan active participant in the design andmanagement of patient adherenceprograms carried out by PCC HELLAS,supervises all personnel involved in patient support, and receivesdaily feedback from patients and healthcare professionals.Email: ztzi@pccint.euConstantina Georgaki, ClinicalPsychologist, PCC HELLAS. Constantinais involved in the development andimplementation of patient adherenceinterventions for populations facing avariety of health conditions. She is alsoinvolved in the patient support centre,conducting one-to-one communication with patients andcaregivers. Her other areas of special interest include relaxationtraining and crisis intervention. Email: dgeo@pccint.eu26 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Regulatory & Market Placewww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 23

TherapeuticImproving Adherence to Inhaled Therapies;Telemonitoring of Dosing Frequency and TechniqueTelemedicine, in its most general sense the practice of“medicine at a distance”, was hailed in the mid-1990s asa potentially time- and cost-effective means of providingpatient care. Today telemedicine utilises electroniccommunication and information technologies whichencompass the electronic transmission, storage, and retrievalof digital data. Telemedicine-based approaches offer anopportunity to address aspects of patient care which havetraditionally proven difficult to monitor and improve.Patient adherence is one such aspect; the World HealthOrganisation (WHO) suggests “improving adherence mightbe the best investment for tackling chronic conditionseffectively”, implying that non-adherence to prescribedmedication is amongst the most influential factorsaffecting health status 1 . Respiratory therapies present aparticular challenge, given the demand for adherence, andalso compliance with correct technique; it is not difficultto appreciate that administering aerosol via a nebuliser,pressurised metered dose inhaler (pMDI), or dry powderinhaler (DPI) is more complex than simply swallowing a pill.The use of a respiratory device is often not intuitive, and whilean average patient’s compliance errors may be less extremethan firing the pMDI directly onto the chest, or swallowingcapsules intended for a DPI, basic errors in technique remaincommon, and can dramatically reduce drug delivery. Forthis reason, True Adherence ([% adherence to prescribedregimen x % compliance with correct use] / 100) is proposedas a preferable global measure of medication delivery inrespiratory patients 2 .Factors underlying poor True Adherence are likely tobe multiple, and involve an interaction between aspects“extrinsic” to patients – relating to the healthcare systemor therapy itself – and more “intrinsic” influences, such asthe patients’ attitudes and demographics. Notably, thosepatients who are “unwitting” or have low levels of literacymay be unaware of their poor True Adherence.Interventions designed to empower patients in thepractice of self-management are likely to be more beneficialthan more paternalistic approaches to adherence promotion.A prerequisite for assessing True Adherence is the abilityto accurately monitor medication use; today, electronicmonitors represent the “gold-standard” for such monitoring.In respiratory patients the feedback derived from monitoringmay also be a valuable method for improving adherence, whileproviding a key to unlocking the complex reasons underlyingan individual’s adherence behaviours. Telemedicine-basedinterventions, which monitor whilst also providing adherenceand compliance-related feedback, have the potential toimprove poor True Adherence and, ultimately, disease control.This article reviews current methods designed to monitorand promote True Adherence, and explores the potentialof telemedicine-based systems. We discuss the evidencefor the benefits of systems such as I-neb Insight Online, aTrue Adherence focused telemedicine-based system, whichTable 1. Factors which may underlie poor True Adherencecombines real-time feedback with the opportunity to promoteand improve adherence in respiratory patients.Historically, interventions aimed at addressing patients’self-management and medication use have focused onadherence alone. It is only recently that reliable compliancemonitors have been developed and many of these devicesare not commercially available outside of clinical trials.Assessing the impact of an adherence intervention onrecorded adherence alone is arguably meaningless, giventhat the intention of improving adherence is to demonstratemeasurable benefits in health outcomes. In view of this, a 2007systematic review assessed longer-term (minimum six monthsfollow-up) randomised controlled trials which attempted tocorrelate adherence with clinical outcomes in chronic nonpsychiatricconditions 3 . A total of 37 clinical trials met theinclusion criteria; these trials assessed 12 different chronicconditions including HIV, rheumatoid arthritis, diabetes, andcardiovascular disease. Eleven studies focused on respiratorydisease, the majority of which concerned asthma alone, whiletwo covered both asthma and chronic obstructive pulmonarydisease (COPD). The interventions assessed were groupedbroadly into behavioural, informational, and combinedbehavioural and informational.The provision of monitoring and feedback, or reductions indosing demands, were associated with improved adherenceacross the different disorders. However, many studiesdeclined to use electronic monitoring to assess adherence,instead opting for the cheaper, though far less reliable,method of self-report. This may explain why results differedfrom those of a more recent review of studies utilisingelectronic adherence monitoring in respiratory patients,28 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Therapeuticwhich found the provision of feedback to be associatedwith significant improvements in adherence, whilst regimensimplification was not 4 . The beneficial effect of monitoringand feedback reflects the opinion of the WHO which suggeststhat “ongoing communication efforts - may be the simplestand most cost-effective strategy for improving adherence” 1 .Overall, results of the review indicated that studiesemploying informational interventions in respiratory patientswere less successful in improving adherence, comparedwith those using combined informational-behaviouralinterventions.Studies of behavioural interventions alone were generallylimited by the use of poor quality adherence monitoringtechniques; although previously shown to be one of the mostunreliable means of monitoring, self-reported adherence wasthe most commonly used method. More objective measures,including pharmacy records and canister weights, were usedby some of the studies included in the review, althoughneither of these offers any means of detecting whether apatient has incorrectly administered their medication - eitherunwittingly, due to poor compliance, or through “canisterdumping”, wherein patients perform multiple, perhapshundreds, of consecutive actuations prior to a clinic visit, withthe intention of emptying the canister, thereby disguisingnon-adherence. The lack of objective measures of adherencemay be interpreted as a cost-saving issue; it is howeverunfortunate, given that highly accurate adherence monitorsare commercially available.It is plausible that the inconsistencies in the relationshipbetween adherence and clinical outcomes were influenced bythe variable definitions of “adherent behaviour” and the lowaccuracy of the commonly utilised method of self-report.Studies employing validated electronic adherencemonitors have shown some promise. For example, useof Chronolog (Medtrac, Colorado), an early electronicadherence monitor capable of recording the date and timeof pMDI actuations, was associated with an improvement inadherence to inhaled corticosteroids; from week two onwardsthe intervention group showed a significantly higher meanadherence, compared with the control group 5 . However,there was no demonstrable difference in clinical outcomesover the 10-week study period. The Smartinhaler (Nexus6,New Zealand) is a more recent adherence monitor which alsorecords the date and time of pMDI actuation, in additionto providing audible medication reminders and visual cues.When adherence levels, obtained via monitoring with theSmartinhaler, were fed back to paediatric asthma patientsand their carers, a 21 percentage point improvement inadherence was observed, compared with those patients whowere unaware of their adherence level 6 . Improvements in FEV1were also greater in the feedback group; however, baselinedifferences in lung function meant that these changes didnot reach statistical significance 6 . Thus, while the use ofelectronic adherence monitors undoubtedly aids recognitionof poor adherence, devices which record adherence alone donot necessarily improve True Adherence or result in clinicallymeaningful changes in outcome measures.As noted above, to assess True Adherence it is necessaryto also measure patients’ compliance, requiring the useof more sophisticated monitoring devices. Several suchdevices have been developed over the last decade; however,while these have generally been validated, few have beenassessed in clinical trials designed to correlate increasedinhaler competence with disease control, and fewer still arecommercially available. Taken together, these results indicatethat monitoring and feedback cannot be seen as the solutionto poor True Adherence, but rather, an important part of anotherwise multifactorial approach to what is recognised as amultifactorial problem 7 .Telemedicine-based systems, which monitor bothadherence and compliance, and also provide problemorientedfeedback based on that monitoring, may offera means by which to address True Adherence in a suitablymultifactorial way. While various products such as theSmartinhaler, and more recent SmartTrak device (Nexus6)offer reminders, these can address only unconscious nonadherence,and make no attempt to improve compliance.The most sophisticated monitors permit automated, andin most cases, remote tracking of adherence. However, ofdevices capable of monitoring compliance, many are limitedby the generalisability of their use (the Electronic Diskhalerfor example is device-specific, while the MDILog (WestMed,Inc., USA) requires the purchase of modified components).The V3 Datalogger (Philips Respironics, USA) is a compliancemonitor designed for use with pMDI accessory devices. TheV3 Datalogger has shown promise, in terms of providingdetailed and accurate information on patients’ compliance,and has been used alongside radiolabelling studies assessinglung deposition 8 . This offers great potential in terms ofinvestigating the relationship between objectively assessedaspects of inhaler technique, and the adequacy of drugdelivery to the target tissue. However, the Datalogger remainsat the development stage, and is currently not available forremote use.Figure 1.True Adherence; a global indicator of patients’ device usewww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 29

TherapeuticFigure 2. I-neb Insight Online infrastructureOf all the available devices, the I-neb Insight Onlinesystem is unique. I-neb Insight Online is designed for usewith the I-neb Adaptive Aerosol Delivery (AAD) nebuliser(Philips Respironics, UK), and contains a data logger thatcan be connected to a computer 9 . The system can monitoradherence and compliance, facilitate access to this data forphysicians, patients, and homecare providers, and providetreatment-related feedback and support. The previouslydiscussed review did not include any studies of True Adherencein patients with cystic fibrosis (CF) 3 . This is concerning, giventhe complexity of CF treatment regimens, the notoriouslypoor True Adherence reported in these patients, and thelikely impact on morbidity and mortality. True Adherencedata obtained through the use of I-neb Insight Online istherefore also likely to provide an important contribution toour understanding of electronic monitoring, feedback, andTrue Adherence in this population.Patients using I-neb Insight Online can also utilise abreathing trainer within the software, which enables theinteractive practice of long, slow inhalations, therebyminimising treatment times. A recent randomised controlledtrial in CF patients using I-neb Insight Online indicated thatlonger, slower inhalations were associated with a reductionin treatment times of more than 40% 10 . In the same study,the shorter treatment times also had a positive impact onadherence. Shorter treatment times using I-neb InsightOnline have also been shown to correlate with higher levelsof True Adherence 11 , providing evidence that the patient maybe more likely to take a treatment if the associated intrusioninto day-to-day activities is lessened.Data collected via the system is uploaded to a centralserver, where it is accessible to the patient, the patient’shealthcare provider, and a dedicated patient support team 9 .The patient support team is able to monitor compliance withinhalation technique and aspects of device performance.At a subsequent consultation the physician can examinepatterns of dosing, for example frequently missed doses ata particular time of day, or on specific days of the week. Thetransparency of information provided by I-neb Insight Onlinenot only offers an opportunity for the physician to engagein a more informed discussion with the patient regardingbehavioural modification aimed at improving adherence,but may facilitate modification of the treatment burden to amutually agreeable level. It may also help the physician makemore informed clinical decisions on the relative efficacy ofprescribed medication against the patient’s True Adherence30 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Therapeuticlevels. Clinicians have reported that open routine monitoringcan help support patients in maintaining long-term inhalationtherapy, while use of the information recorded can facilitatethe tailoring of treatment regimens to the individual, whichcan also improve adherence 12 . As such, I-neb Insight Onlinecan be seen as uniquely multifaceted, reflecting the needsof the patient, identified from real-time adherence andcompliance data. This system is currently available in the UK,and will be rolled out across Europe over the coming months.In the previously mentioned handling study, use of I-nebInsight Online in adult CF patients was associated with98% compliance, and 69.4% adherence, resulting in amean True Adherence of 68% 9 . This compares favourablywith the recently reported adherence level of 36%, alsorecorded in adult CF patients using data downloads obtainedfrom the I-neb AAD System 13 . While such a comprehensivetelemedicine system has not yet been developed and trialledfor use in other respiratory disorders, the potential impactof I-neb Insight Online on True Adherence in CF suggeststhat similar systems may also aid treatment optimisation inconditions such as asthma and COPD.Further indication for the potential of telemedicinesolutions in chronic conditions is derived from the UK’sWhole System Demonstrator (WSD). The WSD, the largestrandomised controlled trial of telehealth to date, involvedthe remote monitoring of vital signs in patients with COPD,coronary heart disease, and diabetes. Recent results werepromising, claiming significant reductions in mortality,hospitalisations, length of hospital stay, and overallhealthcare costs 14 .Monitoring vital signs may be seen as a reactive“firefighting” approach to telehealth, which clearly differsfrom I-neb Insight Online’s more proactive focus on TrueAdherence. However, combining the use of I-neb Insight Onlinewith the monitoring of vital signs for the early detection ofexacerbations, and other facets of CF treatment such as dietand physiotherapy, may offer an opportunity for optimisingthe integrated management of the major complicationsof CF. Depending on health status and behaviours of theindividual, certain patients may benefit from specific aspectsof telemedicine alone. However, for those patients withcomplex multisystem disorders, or multiple comorbidities,a combined approach has tremendous potential to addressthis highly challenging area of disease management.References1. Sabate, E. Adherence to long-term therapies: evidence foraction. Geneva: World Health Organization (2003). http://www.who.int/chronic_conditions/en/adherence_report.pdf,visited 13 November 2012.2. Nikander, K., Arheden, L., Denyer, J. & Cobos, N. Parents’adherence with nebulizer treatment of their children whenusing an Adaptive Aerosol Delivery (AAD) system. J. AerosolMed. 16;3, 273-281 (2003).3. Kripalani, S., Yao, X. & Haynes, R.B. Interventions to enhancemedication adherence in chronic medical conditions. Arch.Intern. Med. 167;6, 540-550 (2007).4. Nikander, K., Pearce, L.J., Smith, N.J. & Pritchard, J.N. Theimpact of electronic monitors on patients’ adherenceto inhaled medications. Dalby, R.N., Byron, P.R., Peart, J.,Suman, J.D. & Young, P.M. (Eds) Respiratory Drug Delivery,2012. Phoenix, Arizona., Davis Healthcare InternationalPublishing, River Grove, Illinois. 3, 673-678 (2012).5. Onyirimba, F., Apter, A., Reisine, S., Litt, M., McCusker, C.,Connors, M. & ZuWallack, R. Direct clinician-to-patient feedbackdiscussion of inhaled steroid use: its effect on adherence. Ann.Allergy Asthma Immunol. 90;4, 411-415 (2003).6. Burgess, S.W., Sly, P.D. & Devadason, S.G. Providing feedbackon adherence increases use of preventive medication byasthmatic children. J. Asthma. 47, 198-201 (2010).7. Lareau, S.C. & Yawn, B.P. Improving adherence with inhalertherapy in COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 5,401-406 (2010).8. Devadason, S., Murdzoska, J., Ditcham, W., Roller, C., vonHollen, D. & Nikander, K. Lung deposition of 99mTc-DTPAfrom a pressurised metered dose inhaler and valved holdingchamber, used with facemask or mouthpiece in childrenwith stable asthma - A pilot study. (2012). http://www.rcjournal.com/abstracts/2012/?id=1433375, visited 16November 2012.9. Spencer, T., Daniels, T., Pollard, K., Agent, P., Morgan, G.,Madge, S., Bilton, D. & Peckham, D. I-neb Insight Online - Atelemedicine option in the treatment of cystic fibrosis. J.Cystic Fibrosis. 11(Suppl 1), S78 (2012).10. McCormack, P., McNamara, P.S. & Southern, K. A randomisedcontrolled trial of breathing modes for adaptive aerosoldelivery in children with cystic fibrosis. J. Cystic Fibrosis.10;5, 343-349 (2011).11. Spencer, T., Dyche, T., Nikander, K., Smith, N.J. & Pritchard,J.N. The association of true adherence, inhalation time andtreatment time for patients using the I-neb AAD systemin either TBM or TIM. Dalby, R.N., Byron, P.R., Peart, J.,Suman, J.D. & Young, P.M. (Eds) Respiratory Drug Delivery,2012. Phoenix, Arizona., Davis Healthcare InternationalPublishing, River Grove, Illinois. 3, 679-684 (2012).12. McCormack, P., Southern, K. & McNamara, P. Newnebulizer technology to monitor adherence and nebulizerperformance in cystic fibrosis. J. Aerosol Med. Pulm. Drug.Deliv. 25, 307-309 (2012).13. Daniels, T., Goodacre, L., Sutton, C., Pollard, K., Conway, S. &Peckham, D. Accurate assessment of adherence: Self-reportand clinician report vs electronic monitoring of nebulizers.Chest. 140;2, 425-432 (2011).14. Department of Health. Whole system demonstratorprogramme: Headline findings - December 2011.(2011). Gateway ref. 16972 http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_131684, visited 16November 2012.John Pritchard, PhD, is CTO for PhilipsRespironics Drug Delivery, with globalaccountability for the developmentof advanced delivery systems for themonitoring and treatment of respiratorydiseases. He has published widely inthe respiratory drug delivery field, beeneditor to several journals, as well as having served on the boardsof two International Scientific Committees and on InternationalGovernment Advisory Panels.www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 31

TherapeuticAdherence in Chronic Myeloid Leukemia:Results of a Patient-driven Pilot SurveyOptimal adherence to oral cancer therapy is of keyimportance to maximise treatment effectiveness inpatients. With the advance of molecular target therapies,cancer treatment in more and more indications istransforming from in-hospital care towards oral treatmentin an outpatient setting. With cancer becoming achronic disease, patients are often required to take thedrug indefinitely on a daily basis. Ensuring an optimaladherence to treatment over the long-term period couldbe a challenge. As data on the driving factors of nonadherencein oncology is scarce, a pan-European workgroupof the CML Advocates Network has conducted a pilot studywhich has unveiled differences of non-adherence betweencountries, administration types and use of adherence toolsin Chronic Myeloid Leukemia. This pilot study has providedthe groundwork for a larger global adherence study that iscurrently ongoing in 12 languages.BackgroundChronic Myeloid Leukemia (CML) has been pioneeringtargeted therapies in cancer, and since Imatinib’s broadavailability in 2001, the effect of intentional and nonintentionalnon-adherence has been observed. Noens et al.(2009) first demonstrated that non-adherence to Imatinibis very common and associated with poorer response totreatment. More recently, Marin et al. (2010) found acorrelation between low adherence rate (less than 90%)and the six-year probability of achieving a major molecularresponse (MMR). In addition, non-adherence was found to bethe main reason for losing response to CML treatment. Thesestudies emphasise that strict adherence to the prescribedImatinib dose is key to ensuring treatment effectiveness inpatients with CML.There is not much literature on potential reasons fornon-adherence to oral anti-cancer treatments (Ruddy, 2009).Even less data is available on reasons why CML patients mightbe non-adherent to Imatinib therapy (Breccia, 2011; Eliasson,2011). A number of factors may influence compliance to oralmedication regimens (Partridge et al., 2002). These not onlyinclude treatment-related aspects but also individual patientcharacteristics and personal factors (Ruddy et al., 2009) aswell as patient education, supporting self-management ofpatients and engaging their social network (EBMT NursesGroup, 2011). A recent study has also revealed that only 53%of CML patients reported strict adherence, with adherencebeing influenced by the availability of patient information,social support and concomitant drug burden (Efficace et al.,2012).Both intentional and non-intentional non-adherence inCML are very common, but so far, the reasons, as well asthe feasibility of supportive adherence tools, have not beeninvestigated in depth.For this reason, the CML Advocates Network, a globalnetwork of 68 leukemia patient advocacy groups in 55countries, has run a pilot survey to gain greater understandingof CML patients’ attitudes and behaviours surroundingadherence, and to develop the questionnaire for a larger studyto ultimately support physicians and patients to improvecompliance and to develop adherence tools. Given thelimitations of a pilot survey with small participant numbers,the primary objective was to confirm the accessibility andusability of the questionnaire in anticipation of a broader,global survey.MethodologyThe pilot survey was provided in eight languages: Czech,Dutch, English, French, German, Hebrew, Italian and Polish.The questionnaire was developed by patient advocates andCML experts with in-kind logistical support from Bristol-MyersSquibb. Local CML patient advocacy groups disseminatedthe online questionnaire, based on a SNAP Surveys technicalsurvey platform, to 10-20 CML patients per country. Thesurvey data was compiled and analysed by an independentstatistician. To determine whether the pilot survey measuresare reliable, Cronbach’s alpha was employed to assess theconsistency and reliability of the data results across thesurvey. A Cronbach’s alpha of 0.81 was produced, indicatingan expectation of CML duration to be strongly associatedwith CML medication duration. This suggests that there issome level of reliability and consistency within the survey.Given the pilot survey’s design and distribution methods,the results are biased as the recruitment addressed rathereducated, informed, younger, active patients who are online.DemographicsIn total 150 total online responses from 10 different countrieswere received over a period of two weeks. Austria (n=1),Czech Republic (24), France (21), Germany (25), Israel (25),Italy (19), Netherlands (18), Poland (11), Switzerland (1) andUnited Kingdom (5). The responses reflect the general CMLpatient demographics, with the majority (96%) of patientshaving CML in chronic phase, a relatively even split betweenmale (46.3%) and female (53.7%). The average age ofrespondents was 51 years.ResultsOf note is that the pilot survey was not powered to bestatistically significant. The pilot was designed to confirm theusefulness of the questionnaire and to develop indicators foran upcoming broader, statistically significant research work.However, the pilot survey already indicates that theremight be substantial differences in adherence acrosscountries. When asked whether patients missed at least onedose within the past month, non-adherence rates varied from32 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Therapeutic18% (Poland) to 33% (Netherlands). Self-reported overalladherence in general was even lower in most countries,with 8% (Germany) to 36% (Poland) of patients claimingto take their medicines strictly as prescribed (see Figure 1).Interestingly, patients tend to wrongly estimate their ownadherence, as evidenced in the difference between patients’reported perception of their own adherence behaviour andthe reported instances of actual missed doses.Figure 1: Missed dose (for any reason) and self-reportedadherence level by countryIn 2009, three tyrosine kinase inhibitors were approvedtherapies: Imatinib, which was the gold standard for firstlineCML treatment and is usually administered once dailywithout having any food effects. So-called approved secondgenerationdrugs were Nilotinib, which is taken twice dailywith two hours fasting before and one hour after, andDasatinib, a once-daily oral drug without food effects. Bythe time of the survey, the second-generation drugs Nilotiniband Dasatinib were usually administered as a second-linetreatment after Imatinib failure or intolerance, but not as afirst-line treatment. Given administration regimen, side-effectprofiles and the psychological impact of first-line failure mayboth be interesting influence factors of adherence, so thesurvey looked at differences in adherence between thesetypes of treatments.The majority of respondents were taking Imatinib (72%),while fewer were taking a second-generation tyrosine kinaseinhibitor (26%). There was no difference in overall adherencebetween the medications (25% adherence on Imatinib, 23%on second-generation treatment). However, the reasons formissing doses appear to vary by treatment and intention:24% of Imatinib patients missed the doses accidentally, whileonly 15% of patients treated with second-generation drugsforget to take their pills. In contrast, only 7% of Imatinibpatients but 21% of patients with second-generation drugsconsciously decided not to take their drug as prescribed.As forgetting to take the medication is the mostcommon reason for non-intentional non-adherence, a largeproportion of patients is interested in tools to improve theiradherence. Patients were asked whether they use, or woulduse if available, alarm clock reminders, mobile phone-basedreminders, reminder phone calls, email reminders, remindersfrom doctors during appointments, reminders from familymembers, magnets at refrigerators or medication dispensers.As Figure 2 reveals, family members reminding patientsto take their medicine (41%), medication dispenser boxes(36%) and SMS reminders (19%) are the most frequentlyused tools today. An additional 11-20% of patients wouldwant to use these reminder tools if they were available tothem. At the same time, there is a large proportion of patientsthat reject these tools, with email reminders (92%), phonecalls (83%), health professionals and alarm clocks (76%)being least popular. This may indicate that a significantproportion of patients do not want to be reminded in theirdaily life that they have cancer.DiscussionThe pilot survey indicates that a significant proportionof patients tend to overestimate their own adherence totherapy. In other words, their perceived adherence differsfrom how often they report missing or skipping doses. Also,the difference on intentional and non-intentional nonadherencebetween first- and second-generation CML drugs,and subsequently the different motivation for adherencebetween first- and second-line treatment, prove the need forfurther needs for research on the drivers of non-adherence.A significant proportion of patients use tools to increasetheir adherence, but there is a large group that feels theseFigure 2: Actual use, willingness to use and rejection of adherence tools34 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Therapeutictools are not yet available to them. However, there is nosingle adherence tool for everyone, which is demonstratedby a large rejection rate of all tools in some groups. A morestatistically significant survey may provide insights into whichtools might work best for certain subpopulations within thepatient community.Overall, the pilot survey has strengthened our thinkingthat there are certain country-specific characteristics, druganddisease-phase-related factors, as well as different driversand tools influencing intentional and non-intentional nonadherence.The next phase of this research work, run by a workgroupof eight European CML patient advocates and two CMLexperts from European countries, is currently underway. Thesurvey is conducted online and offline and intends to haveat least 2000 respondents. The questionnaire was deployedon 22 September 2012 in 12 languages (English, Spanish,German, French, Italian, Portuguese, Finnish, Dutch, Czech,Hebrew, Polish and Russian), with more than 1600 patientsfrom 73 countries having responded in the first eight weeks.To minimise the online recruitment bias, clinicians in threenational CML research groups - GIMEMA in Italy, FI LMC inFrance and the German CML Study Group - are cooperatingwith the CML Advocates Network to distribute hard-copyquestionnaires to CML patients in addition to the onlinesurvey. Results of the study are expected to become availablein spring 2013.ReferencesAerts E, Kellerhals SD, Fliedner M (2011): Adherence to oralanti-tumour therapies. EBMT Swiss Nurses GroupBreccia M, Efficace F, Alimena G (2011): Imatinib treatment inchronic myelogenous leukemia: What have we learned so far?Cancer Lett 300(2): 115–121Efficace F, Baccarani M, Rosti G, Cottone F, Castagnetti F, BrecciaM, Alimena G, Iurlo A, Rossi AR, Pardini S, Gherlinzoni F, SalvucciM, Tiribelli M, Vignetti M, Mandelli F (2012): Investigatingfactors associated with adherence behavior in patients withchronic myeloid leukemia: an observational patient-centeredoutcome study. British Journal of Cancer: 2012.348Eliasson L, Clifford S, Barber N, Marin D (2011): Exploringchronic myeloid leukemia patients’ reasons for not adhering tothe oral anticancer drug imatinib as prescribed. Leuk Res 35:626–630Marin D, Bazeos A, Mahon FX, Eliasson L, Milojkovic D, BuaM, Apperley JF, Szydlo R, Desai R, Kozlowski K, Paliompeis C,Latham V, Foroni L, Molimard M, Reid A, Rezvani K, de LavalladeH, Guallar C, Goldman J, Khorashad JS (2010): Adherence is thecritical factor for achieving molecular responses in patients withchronic myeloid leukemia who achieve complete cytogeneticresponses on imatinib. J Clin Oncol 28: 2381–2388Noens L, van Lierde MA, De Bock R, Verhoef G, Zachee P,Berneman Z, Martiat P, Mineur P, Van Eygen K, MacDonaldK, De Geest S, Albrecht T, Abraham I (2009): Prevalence,determinants, and outcomes of nonadherence to imatinibtherapy in patients with chronic myeloid leukemia: the ADAGIOstudy. Blood 113: 5401–5411Ruddy K, Mayer E, Partridge A (2009): Patient adherence andpersistence with oral anticancer treatment. CA Cancer J Clin 59:56–6AcknowledgementsThe pilot survey on CML Adherence was developed and run by aworkgroup of the following CML patients and experts:• Giora Sharf, Chair of the Adherence Workgroup / CMLAdvocates Network / Leukemia Patient Advocates Foundation,Switzerland / Israeli CML Patients Organisation• Jan Geissler, CML Advocates Network / Leukemia PatientAdvocates Foundation, Switzerland / LeukaNET, Germany• Felice Bombaci, Gruppo AIL Pazienti Leucemia MieloideCronica (Italy)• Mina Daban, President, Leucémie Myéloide Chronique France(France)• Anna Span, Editor LeukoNiews, Stichting ContactgroepLeukemie (Netherlands)• Audrey Denis, Secretary, Vivre Avec La LMC (France)• Tony Gavin, Director of Campaigning and Advocacy,Leukaemia CARE (UK)• Dr Lina Eliasson, Research Associate, Centre for Haematology,Division of Experimental Medicine, Imperial College London(UK)• Dr Fabio Efficace, Chairman GIMEMA Working Party onQuality of Life (Italy)• Dr Joëlle Guilhot, Biostatistics, INSERM CIC 802, UniversityHospital of Poitiers (France)The workgroup received in-kind logistical support from Bristol-Myers Squibb.Jan Geissler is co-founder of the globalCML Advocates Network, co-founderand vice president of the LeukemiaPatient Advocates Foundation, andchair of Leukaemie-Online in Germany.He is Director of the European Patients’Academy on Therapeutic Innovation,and is acting as a patients’ representative in various steeringcommittees and advisory boards.Email: jan@cmladvocates.netGiora Sharf is co-founder of the globalCML Advocates Network, co-founderand treasurer of the Leukemia PatientAdvocates Foundation, and chair of theIsraeli CML Patients Organization. Email:giora@cmladvocates.netThe patient-run CML Advocates Network connects 68leukemia patient organisations in 55 countries on allcontinents. The network facilitates the sharing of bestpractice in CML patient advocacy, organizes an annualGlobal CML Advocacy Summit, and collaborates withresearchers and clinicians.www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 35

TherapeuticWhy Illness Perceptions Count in Heart HealthHalf of all patients hospitalised with a serious heartcondition will make mistakes with their medications withina month of checking out of the hospital, says the latestresearch from Vanderbilt University Hospital and Brighamand Women’s Hospital in Boston. 1 To investigate this issue,Clare Moloney, a Health Psychology Specialist with a focuson cardiovascular health, explains the ‘patient perspective’and tells us why – and how – we can help to tackle this issue.The Cost of Poor Heart HealthThe economic impact of coronary heart disease (CHD) inthe UK alone is huge, costing taxpayers an average of £1.7billion each year. Loss of productivity has even greaterconsequences: more than £3.9 billion in 2006, with 65%attributed to death and 35% to CHD-related illness. 2There is evidence to demonstrate that adherenceto prescribed medication in conjunction with lifestylemodification greatly improves patient outcomes. 3Conversely, non-adherence has the opposite effect. So itis important to understand what holds patients back fromtaking their medications as prescribed.Discovering What Really Drives PatientsResearch that considers the real issues around treatmentnon-adherence in Acute Coronary Syndrome (ACS) – whichis an umbrella term used for patients who have had aheart attack or episode of unstable angina, has revealedinsights into how patients cope with this condition, andhow we can aim to support them. This research involved aliterature review that was commissioned, alongside patientand Healthcare Provider (HCP) research, to uncover the realdrivers of non-adherence in this patient group.Adherence Challenges in Heart Health - RevealedThe research uncovered some interesting findings, and aswith all illnesses there were a variety of patient perceptionsand beliefs that led to non-adherence:• “I was only in hospital for a couple of days; it can’t bethat bad”Although the implications of having a heart conditionare very serious, advances in treatment means that manypatients may now only spend a short time in hospitalfollowing an episode, leading to a misunderstanding aboutthe seriousness of the condition.• “Well, that’s it for me…”Research found that patients who feel a lack of controlfollowing hospitalisation and diagnosis could be ‘fatalistic’,taking the view that nothing can help their condition: eithermedical treatment or lifestyle changes.• “Who are you to tell me?”Other patients may find it hard to accept their diagnosis(particularly those who are largely asymptomatic) andtherefore find it hard to accept their diagnosis or choose torebel against the advice given as a way of avoiding facingthe ‘truth’ about what has happened to them.• ‘I was so shocked, everything’s just a blur”For many people, receiving information at hospitaldischarge or in the very first recovery phases is too early. 4Patients who have very recently had a myocardial infarction(MI) or received a CHD diagnosis may not be able to absorbimportant information fully due to post-traumatic stress oran emotional response to their illness.This can impair their cognitive ability to the extent thatthey cannot understand how to manage their medicine andlifestyle changes. 536 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 35

TherapeuticPractical Pain Management in Older PeopleIntroductionPain relief, whether acute, chronic or related to surgery, isan issue throughout the world. However, as a result of achanging population demographic in countries like the UK,the proportion of older patients is increasing, which posesunique challenges when considering analgesia. We have apotential aging ‘time bomb’ and we need to prepare ourservices to meet the needs of this older age group ensuringtheir dignity and their well-being not compromised. Hence,five years ago the British Pain Society worked with theBritish Geriatrics Society & the Royal College of Physicians,reviewed the evidence and produced national guidance tohelp all practitioners in assessing pain in older people with asimple algorithm in October 2007 (Ref. 1 & Appendix 1). Thepurpose was to provide professionals with a set of practicalskills to assess pain as the first step towards its effectivemanagement.To put the effects of pain in the elderly in perspective,national UK statistics have indicated that pain or discomfortwas reported by about half of those over 65 years old, and56% of men and 65% of women aged 75 years and over.Higher prevalence estimates are obtained from samples ofinstitutionalised older people, where 45–83% of patientsreport at least one current pain problem.Pain AssessmentCompared to young adults some of the challenges arecognitive impairment, communication, language and culturalbarriers. Box 1 in that report lists the key components like:direct enquiry, observations of signs, description (sensory,affective & its impact), measurement & cause of pain. Theirtable 1 & 2 describe the observational changes associatedwith pain & various scales for assessing pain.Assessment of pain may be carried out by normal methodsand conventional numerical or graphical methods work well.However, impairment of higher intellectual functions maymean that observational techniques may also be needed.Key components of an assessment of pain include directenquiry about the presence of pain and observation forsigns of pain, especially in older people with cognitive /communication impairment. Description of pain shouldinclude the sensory dimension, the affective dimension(e.g. fear, anxiety or depression) and impact on the patient.Measurement of pain should ideally use standardised scalesin a format that is accessible to the individual. Of course theaim of history, examination and investigation is to establishthe cause of pain, in order to effect treatment (Box 1).Observational changes associated with pain can also bemore marked (or subtle) in the elderly, including autonomicchanges, facial expressions and body movements. Aggressiveverbalisations / vocalisations and altered interpersonalinteractions can sometime be the presenting complaint ofthose with pain, especially if there is preceding cognitiveimpairment. Changes in activity patterns and mental statuschanges can sometimes also occur (Table 1).Our experience at NELTCWe at NELTC have standardised the process along theentire surgical care pathway (from pre-assessment, throughadmission on the wards, theatre & recovery to dischargehome and follow up) with a Coloured Visual Analogue Scale(Appendix 2). Pain maps are sometimes used to get moredetails on localisation as in some patients with chronic pain(Appendix 3). Our numeric rating scale from 0 to 10 is used40 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Therapeuticin those patients, with some difficulties, who are able to useverbal descriptor 0 to 5 scale by converting it to 0 to 10 whilerecording it (Appendix 4). We found this standardisation tobe very helpful in doing our routine recording of pain scoresby our nurses on the wards, and also in the Pain & SicknessAudit carried out by us based on their records. This auditshowed us excellent pain & sickness scores, with a highpatient satisfaction rate, compared to world literature & waspresented at various conferences in Birmingham (BAPIO),Wembley (BAOIA), Tel Aviv (ISA), Mumbai (ISA) & Granada(WSPC) and well received by the audience 2 . We followedthe recommendations of the National Guidelines whichare summarised (Appendix 5) along with the algorithm(Appendix 1).Management of Acute Postoperative PainThree years ago European Society of Regional Anaesthesiaand Pain Therapy produced general recommendations andprinciples for successful pain management postoperatively 3 .Effective pain management is a very important part ofmodern surgical practice. The goals are to: improve quality oflife, rapid recovery & early discharge with minimum morbidity.Listening to and believing in patient is the first step. Useof one scale within a hospital ensures that everyone in theteam ‘speaks the same language’ of intensity of pain, frompre-assessments, wards, recovery to discharge time. This alsohelps in adjusting drugs for better pain management 4 .Informed consent ensures detailed discussion about painand its treatment. To keep realistic expectations of carepatient participation is important and they need to knowabout ‘pain relief’, not a ’pain free status’. In addition toverbal information wall posters in the clinics / wards andpatient leaflets are useful.As the mechanism of pain is multi-factorial these daysmultimodal analgesia is recommended for a balancedcombination of analgesics, co-analgesics & local anaesthetic(LA) blocks or infiltrations. Surgeons routinely use localanaesthetics before or after (preferably both), with or withoutother form of anaesthesia to improve pain control. Using LAbefore incision means patient’s analgesic requirements &side-effects are reduced, especially in those older patientswith multiple co-morbidities.The elderly present special problems in the provisionof analgesia. As a general rule, the elderly report pain lessfrequently and require smaller doses of analgesic drugs toachieve adequate pain relief. Many patients are anxious,which may be associated with increased pain postoperatively.Commonest drugs in use are Paracetamol, NSAIDs,Gabapentin / Pregabalin, Codeine, Tramadol, Oxycodone,Morphine in various combinations, through a step by stepapproach depending on the severity of pain & patient’stolerance / intolerance of drugs. Drug dose for each drugprescribed needs to be tailored to patient requirementsespecially taking their age and age-related metabolic changesin consideration. Coxib or NSAIDs are used with caution inolder people usually with proton pump inhibitor and routinelymonitored for drug interactions, gastrointestinal, renal &cardiovascular side effects.NSAIDs (e.g. diclofenac, ibuprofen and naproxen areamongst the most widely used medications globally foranalgesia, particularly in patients with rheumatologicalconditions, but they can have serious side effects. Uppergastrointestinal disorders ranging from heartburn anddyspepsia are more common to peptic ulceration andgastrointestinal bleeding. Care should also be taken in patientswith compromised hepatic or renal function. These drugs canalso cause raised blood pressure, as well as leading to heartfailure and myocardial infarction in high-risk patients, firstdetected in studies of selective cyclo-oxygenase inhibitors.Self-medication with opioids is not always wise in elderlypatients and thus the role of patient-controlled analgesia maybe limited. The elderly may be particularly sensitive to opioidsand side effects such as confusion, sedation and respiratorydepression assume greater importance. Because of changes inhepatic and renal function lower doses of opioids are neededand the expected length of action may be longer.Only one analgesic drug should be used at a time in theelderly. In general about half the normal adult dose, evenless in very old, should be given at first, especially if the drugis being given intravenously. Small doses should be givenregularly to anticipate pain where appropriate.www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 41

TherapeuticWhen analgesic drugs are given they may not be absorbedas well or metabolised as efficiently. In practical terms, dosesof drugs such as NSAIDs and opioids in the elderly shouldbe reduced because of a decrease in liver metabolism. Inaddition, since the metabolites of drugs such as morphine andpethidine are excreted by the kidneys, any decrease in renalfunction may lead to accumulation with repeated doses. Theelderly are more likely to be receiving more than one drugfor underlying medical conditions and the possibility of druginteraction is also greater.Spinal anaesthetic (LA + opioid) is now generally morepopular than Epidural, and LA infiltrations are becoming morecommon than Nerve Blocks. For intra-articular LA infiltrationssome adrenaline, NSAID & opioids maybe indicated forbetter results than LA alone. Some of these drugs also help inreducing the incidence of the pain becoming chronic (beyond3 months after surgery).Nerve blocks are a most effective way of givingpostoperative pain relief. Intercostal nerve block can aidpulmonary function after chest or upper abdominal surgeryand pain below the waist can be abolished by epiduralblockade aiding the return of gastrointestinal function aftersurgery. However, blocks spread more widely in the elderlyand there may be compromise of respiratory function due tointercostal paralysis. In addition, a greater sympathetic blockmay occur with a consequent fall in blood pressure. With care,local anaesthetic blocks can be very useful in the elderly andgive excellent pain relief whilst permitting mobilisation andrehabilitation by physiotherapists.Non-pharmacological treatments like cold therapy withiced water bag on the joints seem to help reducing theswelling as well as pain. Fewer analgesic drugs are required,as we move towards enhanced recovery from surgery.We have regular meetings of Anaesthetists Group and PainGroup to continue to update and improve with latest evidenceand mutual agreements. Daily multi-disciplinary ward roundsheaded by an anaesthetist (with overall responsibility) havebeen valuable for some of the improvements in quality oflife, reduced morbidity, rapid enhanced recovery and earlydischarges. Older patients in particular may need more timecommitments and mutual co-operation from all staff in amulti-disciplinary set up.Management of Chronic PainProfessor Schofield and colleagues produced a paperreviewing the main recommendations within the guidelinesby the BPS & BGS 4 .Any pain beyond three months by definition is chronic.Prevalence of any pain in older persons is 0 to 93% by variousestimates carried out, according to this joint report. Currentpain ranged from 20-46% in the community & 28-73%in residential care. Chronic pain prevalence ranged from25-76% in community & 83-93% in residential care.Women have a higher prevalence than men.The three most common sites of pain in older peoplewere: back, lower limb and other joints. This shows thatmillions of people live with chronic pain as if it is ‘expectedto be part of ageing’ that they are ‘learning to live with’.In addition to the drugs for acute pain these patientsmight need the following, initially in lowest doses: Tricyclicantidepressants, anti-epileptics, gabapentin / pregabalin,with prophylactic anti-emetics and laxatives.Interventional therapies showing benefits in wellselected cases by Pain Clinicians include facet jointradiofrequency lesioning and intra-articular corticosteroidsor hyaluronic acid injections. In acute herpes zoster &post-herpetic neuralgia LA infiltration or nerve block withLA & corticosteroids is effective. In trigeminal neuralgia inolder people percutaneous procedures are preferred overmicrovascular decompression.Psychological approaches like cognitive behaviourtherapy (CBT) has some role and maybe relaxation,meditation, mindfulness etc.42 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

TherapeuticEthical & Legal Aspects of Pain managementWhile assessing & managing pain in older people someimportant aspects of ethics and law need to be kept at theback of our minds 5&6 .Firstly, it is now important that the consent is as informedas possible, with patients having rights to refuse. Consent invarious situations and in different age groups, from cradleto grave, is discussed. 7&8 On the basis of the Data ProtectionAct 1998, Confidentiality is considered along with expressconsent. Risk Management includes statutes such as theMedical Acts, NHS Acts and the Health & Safety at WorkAct.It is suggested that we use Complaints Management fromlocal resolutions to legal proceedings and ADR, in the light ofLord Woolf’s Reforms. Importance of good quality (Medical/ Anaesthetic / ICU / Pain / Clinic / Hospice / Hospital)records is stressed in medical defence of any unfortunateincidents 9&10 . From Bolam to Bolitho is the considerationon Clinical Negligence. Here the importance of practisingwithin the issued guidelines from public authorities, likeNICE, GMC, Royal Colleges or Boards, WHO, UN andinternational evidence based medical (EBM) practice, isstressed. Over 40 years of practice and experiences fromthe USA, Canada, Europe, Balkans, Australia, New Zealandand India help us do a global comparison but we still needto tune into national guidelines, especially those drawn upby experts like BPS,BGS, RCP.If we visit a virtual courtroom to study civil, militaryand criminal cases and the law governing those MedicalWitnesses and Medical Experts we will see various typesand grounds of Discrimination including the latestdevelopments in this highly prevalent, but preventable, areaof Employment Law. An LLM project on ‘Race Laws in theNHS’, and experience in the BMA Medical Ethics Committeeare briefly mentioned.A very significant shift in English Law, due to a Europeanintroduction (from October 2000) of the Human Rights Act1998, is highlighted 11,12,13 . With this knowledge we thentry to predict the likely impact on the Pain Practice withall its sub-specialties. We will certainly be looking forwardto any suggestions for tackling information overloadwhile continuing to practice evidence-based, safe painmanagement, anaesthesia and critical care for our olderpatients! Let the Medical Law continue to evolve in the Westand be lead by Ethics from the East, based on Bhagavad-Gita 14 .Recommendations & ConclusionBased on our recent experience & developments locally werecommend that the following steps will help us move in theright direction for better pain management in older people:1. Institutions to have Strategic Pain Groups for thoseinterested in the topic with a commitment for updates& continuous improvement leading to creating localchampions everywhere.2. To standardise Pain Scales with Pain Maps for betterassessing pain localization & pain intensity.3. On surgical side, to give more emphasis on acute painmanagement including safe use of LA in almost all patients& utilizing the skills of Anaesthetist colleagues.4. On Medical side, to use balanced analgesic combinationsmainly, seeking expert advice from Pain Clinics in chronicor acute on chronic pains or from Psychologists in selectedcases.5. Not to forget the Ethical & Legal issues in pain practicewhile using our National Guidelines.In conclusion, ‘Sarve Bhavantu sukhinah, Sarve santuniramayaah’ meaning let everybody be happy, free of pain& suffering. Let’s aspire to make the world of older peoplefree of pain so we can all look forward to a long & happyretirement too!References1. The assessment of pain in older people National Guidelines(October 2007) by RCP, BGS & BPS.2. Bhala B & Kozma Z, Pain & Sickness Audit in JointReplacement Surgery at NEL NHS TC, Ilford IG3 8YY.Presented at various conferences (2011).3. Postoperative Pain Management – Good Clinical Practice,General recommendations and principles for successfulpain management: by European Society of RegionalAnaesthesia & Pain Therapy (2009).4. Pat Schofield et al, Pain in older adults – guidelines for themanagement (Pain News, June 2012) by, Vol 10 No 2 p.120-122.5. Bhala B, Ethical & Legal Aspects of Pain Managementpresented at various updates & conferences (2011).6. Giordano J. Moral Agency in Pain Medicine, Pain Physician2006:9:41-467. Meisel A. et al. Seven Legal Barriers to End-of-Life Care,JAMA 2000:284:198. Byock I. End of life decisions and quality of care beforedeath, BMJ 2009:339:3579. Shapiro R.S. Healthcare providers’ liability exposure forinappropriate pain management, Journal of Law, Medicine& Ethics 1996:24:360-410. Furrow B.R. Pain Management and Provider Liability:No more excuses, Journal of Law, Medicine & Ethics2001:29:28-5111. Brennan F. et al. Pain Management: A Fundamental HumanRight, Anesth Analg 2007:105:205-22112. Schatman M.E. Ethical Issues in Chronic Pain Management200613. Blacksher E. Hearing from Pain, Pain Medicine 2001:2:169-17514. BHAGAVAD-GITA (www.yatharthgeeta.com).Dr BalMukund Bhala TD, RAMC (V) MD (Anaesthesiology),FFARCSI, MBA (OUBS), LLM in Medical Law (UNN) Care UKConsultant Anaesthetist & Chair, Anaesthetists Group & PainGroup, North East London NHS Treatment Centre, near KGH,Ilford, Essex IG3 8YY. Member of Pain in Older Adults SpecialInterest Group of British Pain Society.Dr Neeraj Bhala MBChB, MRCP, MSc(Epi.), DLSHTM, FRSPHSpecialist Registrar in Gastroenterology and General MedicineQueen Elizabeth Hospital, University Hospitals BirminghamNHS Trust, B15 2TH. MRC Health of the Public Fellow ClinicalTrial Service Unit, University of Oxford, OX3 7LF.www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 43

Modern TechnologyDirect to the ePharma Consumer –In the Age of ConnectivityIt is not a passing fad but a permanent shift. ePharmaconsumers are here to stay. It means that pharmaceuticaland medical device companies must adapt to the new digitalenvironment. While change is inevitable in any industry, thismay be the first time that neither industry nor regulatorsbut rather patients are driving this shift. To understand thehesitancy of the pharma industry and FDA toward direct-toePharmaconsumers, it is helpful to look back 30 years ago tothe advent of direct-to-patient advertising in 1983 in the US,by British-based Boots Pharmaceuticals. The campaign wasfor its prescription brand of ibuprofen [Rufen]. At the time, USregulators and major pharma companies resisted the direct-toconsumerapproach. A two-year moratorium was immediatelyenacted by the Food and Drug Administration (and initiallysupported by most major pharma companies). The moratoriumwas intended to allow regulators time to more fully explorethe ‘risks and benefits’ of going direct to consumer. Whileindustry and FDA viewed it as risky, patients on the other handviewed it as necessary. AIDS and breast cancer activists at thetime were the most vocal patients in voicing their demandsfor the right to become actively involved in their healthcareknowledge and decision-making, and ironically the then USSurgeon General, C. Everett Koop, publicly called for patientsto become “empowered healthcare consumers”.Today, three decades later, in the face of digital marketing,some of the same hesitancy by regulators and industrysurrounds the direct-to-ePharma consumer approach inEurope and the US. But this time in the US and Europe there isa major difference: while FDA deliberates, European agenciesdismiss it, and industry’s legal, regulatory and complianceteams take time to garner institutional knowledge aboutdigital media, patients are already leading the charge anddoctors, medical centres and clinical researchers across theglobe are joining them.Technology is also propelling the broader adoption ofdirect-to consumer strategies globally through the use ofportable digital devices, and it’s happening at warp speed,leaving industry to catch up. Today, internet penetration isover 70% in the majority of countries, enabling over 90%of patients and/or their families to conduct online researchbefore seeking medical intervention. Furthermore, over twothirdsof adults go online looking for broader health- andpharmaceutical-related information.This trend requires industry and more doctors to embracethe most empowered ePharma consumers that either hasever encountered. Constant internet connectivity – togetherwith the rapid adoption of mobile devices – is changing howwe market prescription products and clinical trials direct toePharma consumers, care-givers and others.It’s not a question of if, but when … and the answer isnow.While direct selling to patients through multiple channelshas been around since the US Boots’ TV and print campaignin 1983, recent technology advances have had a significantimpact on consumer behaviour, not only in healthcare but indaily living as well. By 2015, it is estimated that more than50% of all retail sales will be either online or influenced bythe online channel, demonstrating the integral use of theinternet in all aspects of daily living including healthcare.In the traditional model, industry’s principal ‘customer’remains the doctor, who serves as gatekeeper, prescriberand learned intermediary. However, as other industries havefound, their customers - consumers of all ages - are leveragingthe benefits of an integrated, multi-channel approach,offering mobile applications and online options that make iteasy and convenient for customers to execute transactions,access information, and make informed decisions, regardlessof location.Given how quickly patient expectations are rising,direct to consumer models that include mobile-enableddigital strategies in a constantly connected future will helpdifferentiate a product or clinical trial from competitors.Tailored messages and information are delivered by apatient’s choice of communication: SMS, email, automatedvoicemail, direct mail, or a combination. On the commercialside, marketers are finding success in integrating co-paybenefit programmes to individual patient needs, on-demandaccess to experts, and community support.The most successful direct-to-ePharma consumercampaigns are those that foster a more effective dialoguewith patients. Engaging patients online as they are lookingfor information, and integrating that information withprogrammes that are accessible offline and through mobile,is the new model for both the commercial and clinical trialsides of the industry.It’s not just a US phenomenon either. It’s a global one, asempowerment is occurring in countries with traditional socialhierarchies. And while some doctors might prefer patientsnot to be well-informed, patients on the other hand expect tobe able to research and obtain product information any timeand anywhere, using whichever channel (or combinationof channels) they find most convenient. The same goes forclinical trials as well.Direct-to-ePharma consumer marketing requires anintegrated business model where all channels – digital andphysical – work together seamlessly to connect with patientsand guide them to diagnosis, medical specialists, treatmentsand or clinical trials.Today, ePharma consumers want access to conditioneducation in innovative and engaging formats withpersonalised assessments. Condition-specific online videosfor example, bring to life the experiences of real people living44 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Modern Technologywith real conditions — from allergies to Alzheimer’s — aswell as care-givers and expert insights. Videos showcasechallenges, questions, struggles, humour, relationships,and everyday issues of the patient and care-giver journey.For clinical trials, they ease anxiety and address concerns.Importantly, users can come back at their convenience,bookmark it, create their own playlists, rate videos, or send toa friend or family member, further expanding the reach of adirect-to-ePharma consumer campaign.Reaching the ‘connected consumer’, today’s digitalcampaigns must incorporate strategies that addressfundamental behaviours. These ePatient consumers areincreasingly connected• Technically through a wide array of devices,• Socially through ever-expanding social networks,• Medically through online communities of ‘consequentialstrangers’ where ePatients leverage their knowledgewith information exchange, and• Economically through memberships to online pharmaciesthat offer discounted prescriptions and medical supplies.The rapid growth of ePharma consumers has creatednew opportunities to tap into well-defined online patientcommunications channels for pharmaceutical marketersof prescription drugs and those promoting clinical trialsdirectly to patients. A number of factors are driving thegrowth of the ePharma consumer population. Olderconsumers are increasingly using the internet as a searchtool, with prescription drug information of particular interestin this population. In addition, many people now takemultiple prescription medications; in the current economicclimate ePharma consumers are carefully considering theirtherapeutic options. In the US, where medical costs for manyare not paid for by the government, cost-conscious olderconsumers are heading online in search of money-savingcoupons and free trials for FDA-approved treatments, whileother consumers intentionally or by chance seek out clinicaltrials that offer free study-related medical care and treatment,and reimbursement for participation.The rise in online direct advertising has been accompaniedby a decline in offline advertising, with advertisers looking forGuide to developing a successful direct-to-ePharma consumer strategywww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 45

Modern Technologymore innovative, lower-cost alternatives, and the ability tomore precisely reach specific patient populations, especiallyfor clinical trial marketing. For clinical trials, marketers mustfind and connect with very specific subsets of patients thatmeet very specific medical criteria. On the commercial side thisspecificity is generally not required, and direct-to-consumercampaigns target patients therapeutically – diabetes,rheumatoid arthritis, irritable bowel patients. Clinical studyteams who have embraced eMarketing as an integral partof their patient recruitment strategies have generally foundonline media costs to be significant lower, with per-patientrecruitment costs up to six times less than offline advertising.But online marketing success for clinical trials requires theartful use of market data.Succeeding at online marketing is more than simplearithmetic. Instead, a digital marketing team that is wellversedin web-based outreach must interpret various searchengine analytics, and be able to translate that informationinto a nuanced understanding of various search enginecapabilities. Even details such as the direction in whichadvertisements are positioned on a web page can influencethe effectiveness of outreach campaigns. An effectiveeMarketing campaign requires constant and daily attentionand assessment of performance metrics. Dedicated digitalmarketing managers bring a highly-defined skill set that isrequired to truly launch successful digital ePharma consumercampaigns that expeditiously deliver patients to clinical trialsor to a branded product.We have learned over the past several decades of launchingand implementing deeply engaging, supportive, and authenticpatient activation programmes, branded products and clinicaltrials that a continuous supply of resources needs to be readilyavailable for patients at every decision point, from onlineassessment tools, to call centre support and accessing clinicalresearch centres on demand. We also know that different typesof patients behave differently. Online patient communitieshave provided a window into the lives of patients, providingdepth of knowledge that was not possible before. Harnessingthe power of digital media, data and portable technologies cantake direct-to-ePharma consumer campaigns to new heights.Liz Moench, President and CEO ofMediciGroup ® Inc, has developedgroundbreaking patient-centric programmesfor marketed products andclinical trials. Her achievements includelaunching industry’s first direct toconsumer advertising campaign [1983],pioneering patient recruitment for clinical trials, [1991] andoptimising digital and social media for clinical recruitment,including creating some of the largest online patientcomunities; Team Epilepsy, Gout Study, Lupus Team to promoteclinical research. Email: lmoench@mediciglobal.com46 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Drug Delivery, Drug Packaging, Labelling & DispensingA Tool for Designing and EvaluatingPackaging for Healthcare ProductsAbstractAlthough significant resources are devoted to developinghealthcare products that are safe and effectivepharmacologically, significantly less effort is devoted toensuring products perform as intended in the hands ofproviders and patients. Poor designs result in user confusionand frustration, and have the potential to lead to errors andadverse events. The interaction that occurs between peopleand healthcare products is an area in need of study.The human-package interaction framework introduced bythis paper is an analysis tool to support decision-making whiledesigning and evaluating healthcare products. According tothis model, any healthcare product has: a set of intendedusers, varied contexts of use, and a series of tasks that usersmust accomplish (selection of the correct product, opening,administration, reclosing, disposal, etc.). The model providesdesigners with a structured consideration set with regard tothe interactions between people and healthcare products.Considerations to the interface are critically needed in orderto reduce the occurrence of medication errors and increaseadherence. Two examples are described to illustrate theconcepts.KEYWORDS: packaging, usability, adherence, noncompliance,medication errorIntroductionThe American National Coordinating Council forMedication Error Reporting and Prevention (NCCMERP)defines a medication error as “any preventable eventthat may cause or lead to inappropriate medication useor patient harm while the medication is in the control ofthe health care professional, patient, or consumer. Suchevents may be related to professional practice, health careproducts, procedures, and systems, including prescribing;order communication; product labeling, packaging, andnomenclature; compounding; dispensing; distribution;administration; education; monitoring; and use.” 1One way that medication errors manifest themselves isas an adverse drug event (ADE), defined as “injury due tomedication.” 2 By their nature, ADEs can be either preventableor unpreventable. Events that are attributable to productquality defects, medication errors or issues of non-complianceare examples of preventable events, while things that cannotbe foreseen or avoided are unpreventable. Examples ofunpreventable events include things like an unknown allergicreaction to a medication, or unavoidable side-effects, such asnausea and fatigue induced by chemotherapy.Medication errors and non-compliance events are closelyinterrelated. Some researchers have even argued that somenon-compliance events could be considered medical errors. 3Irrespective of how they are classified, both medication errorsand non-compliance issues are, many times, related to poordesign. Consider, for example, the Office of Post-MarketingDrug Risk Assessment (OPDRA, a division of the US Foodand Drug Administration), recommends interventions whichinclude changes in the naming, labelling, or packaging of adrug product. 4Regardless of whether the product is administered by ahealthcare professional, or the patient, there is an importantinteraction which must occur between the human andthe product. However, while a significant amount of timeand resources are devoted to ensuring safety and efficacypharmacologically, the degree to which design impactsthe product’s performance in the hands of patients andcare-givers is given considerably less attention. 5 Healthcareproducts that are designed and evaluated such that theycatalyse medication adherence and minimise errors aresorely needed.The correct and effective use of a drug does not simplydepend on the written information of its labelling and theverbal information given by healthcare professionals; itis supported by a system of physical components such aspackaging, measuring devices, applicators, dosing devices,closure systems, and the drug itself. 6 All these differentparts convey crucial information to patients, and their poordesign is known to be a contributing factor to patient noncompliance6and subsequent adverse events. 7,8 In fact,according to the Medication Error Reporting Program (MERP)operated by US Pharmacopeia (USP) and the Institute forSafe Medication Practices (ISMP), labelling and packagingissues were cited as the primary cause of 33% of medicationerrors, and incited 30% of reported fatalities.A review of the literature suggests that patient confusion andlack of accessibility are at the core of usability problems withmedications:• Confusion due to packaging similarity. 6,8,9• Confusion due to flawed dosing devices. 10• Confusion due to physical drug appearance (e.g., tabletsimilarity). 6• Confusion because of labelling issues: distorted text,non-flat labels, small print, lack of contrast, etc. 6,8• Confusion due to drug naming issues. 8,9,11-13• Non-accessible packaging. 6,14One critical reason for these problems is that the scientists andregulators who have historically made decisions regardingthe design of these systems frequently do not understand thecomplexities of human ability and behaviour. The approachhas generally been product-centered (PCD) in nature. That is,traditional decisions have been driven by the technical needsof the product (i.e., a drug) and manufacturing. Decisionstend to be focused on the manufacturer’s ability to maintain48 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Drug Delivery, Drug Packaging, Labelling & Dispensingthe product’s safety and efficacy throughout the stated shelflife, as well as the need to produce, fill and distribute the drugefficiently. User considerations and abilities generally play asecondary role in terms of importance.We believe a more user-centred design (UCD) approach isneeded. This shift is already beginning, and will likely grow,as the result of:• the costs associated with non-compliance,• global population aging,• changes in the social construct through which we viewdisability,• the need for product differentiation in an increasinglycompetitive marketplace, and• the social dimension of the sustainability movement.A Comprehensive Interaction FrameworkClearly, the interaction that occurs between people (i.e.,users: patients and healthcare professionals) and healthcareproducts is an area in need of study. To provide a frameworkfor creating and evaluating how products perform in thehands of patients and healthcare professionals, we haveadapted and combined commonly accepted models from thefields of cognitive psychology and human factors; HumanProcessor Model15 and Usability Theory. 16The Human Processor Model is a simplified representationof the human mind. It postulates that, in order to processinformation and then act upon it, humans employ threesystems:a) The perceptual system: which handles sensory stimulusfrom the outside world (i.e., the five senses).b) The motor system: which controls actions.c) The cognitive system: which supplies the processing toconnect the perceptual system (input) and motor system(output).The interaction between an object (e.g., warning, label,package, etc.) and a person can be described as a cyclicinformation flow17 consisting of five stages (see Table 1):1. Exposure: the user is exposed to necessary information.Information may be in the form of the pack, features,labelling, or other components of interest.2. Perception: information is input into one or more of thefive senses.3. Encodation: the external information gathered throughperception is transformed into an internal representation.This may be associated with perceived affordances storedin the long term memory (e.g., information from othersources, previous experiences, etc.). Perceived affordancesprovide cues about the operation of things. They referto the object’s characteristics that are perceived by theirusers regarding their potential use. 18 Form, colour, texture,material, and weight of a package incite certain user’sactions.4. Comprehension: the user recognises and assigns meaningto the encoded information, thinks about the effects ofusing the package features, and compares the effect ofthe action with the user’s goals (intentions). Goals maycondition recognition and vice versa.5. Execution: thought is then translated into actions byactivating voluntary muscles. In the case of packagingmanipulations, the most important effectors are the armhand-fingerand the head-eye systems. User’s actions,or reactions, may be instrumental or non-instrumental.Instrumental reactions include the use of a packagingfeature to accomplish a goal (e.g., opening). Noninstrumentalactions include things like touching a surface,etc. The user’s actions may cause a new state of things (e.g.,opening accomplished, now dispensing must occur) andthe cycle repeats until the user’s goals are accomplished.According to Usability Theory, there are four principalcomponents in a “human-machine” system, namely: user, task,tool, and environment; 16 in our argument the “tool” is representedby the design of the packaged product. Since human-packageinteractions can be described by means of information flow,it can be inferred that success or failure at each step of theHuman Processor Model (see Table 1) is dependent on the fourcomponents of Usability Theory (see Figure 1)Table 1 – The five stages of human-package interactionsFigure 1: The four components affecting the five stages ofhuman-package interactions. Adapted from Shackel 161. The user: the characteristics of the person, includingperceptual, cognitive, and physical capabilities, beliefs,habits, previous experience, etc.2. The task: the series of actions and goals to be accomplished,such as identifying, following instructions and directions,opening, dosing, reclosing, storing, disposing, etc.3. The pack: the object of the interaction; the design of thepackage and product.4. The context: the physical and social environment in whichthe interaction takes place. This includes characteristicslike lighting, seating, distractions, temperature, pressures,other people, etc.www.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 49

Drug Delivery, Drug Packaging, Labelling & DispensingThe combination and adaptation of the existing modelsprovides a framework regarding the needs, abilities, anddesires of users with diverse goals in varied contexts. It canbe used to inform the consideration set of variables whichhave the potential to influence adherence when designingfor, or evaluating, package performance.Further, these interactions can be described as an iterativeloop that consists of perception, mental processing, andaction that occurs within a particular context when anindividual needs to perform a specific task (or series of tasks)with a packaged product (see Figure 2). The interaction isa cyclic process in which user’s actions may cause effectsleading to a new state of things, and perception is then reevaluatedin terms of user’s goals.Figure 2: Human-package interaction framework. Adapted from Shackel,Card, and Monk. 15-17Application to Healthcare ProductsDesigners that employ a user-centred design approach willidentify users’ characteristics, contexts of use, and tasksassociated with a healthcare product in order to optimiseperformance. For evaluation and testing purposes, this toolcan be used to define testing conditions and compose userpanels. Contextual conditions for testing include: the physicalenvironment, lighting, temperature, noise, and distractions,for example.For design and development, the framework can supportseveral design research activities such as user observation,ethnography, task analysis, context of use analysis, productbenchmarking, and so on. During design phases like conceptgeneration, prototyping, and testing, designers and engineershave the potential to account for a variety of factorsaffecting the usability of healthcare products. Furthermore,key design strategies are likely to be generated by analysingand prioritising such factors.The model can be used to guide and verify assumptionsregarding the product and the target audience. Designersshould observe and interview actual users carefully in orderto incorporate insights about product use and verify theirassumptions in an ecologically valid context. The nextsections illustrate potential problems of adherence andmedication errors that would benefit from a more usercentredapproach to design.To accomplish this, we use two healthcare products (seeTable 2)Table 2: Summary breakdown of users, contexts of use and tasks for twocommon healthcare productsa) Infant’s and children’s ibuprofen: a situation dealing withdosing and drug identification issues.b) Epinephrine injection: a situation of emergency use.Infant’s and Children’s IbuprofenIbuprofen is a non-steroidal anti-inflammatory (NSAID)analgesic antipyretic (lowers body temperature withoutimpairing consciousness) that, at higher doses, reducesinflammation. Our example utilises two formulations, onefor infants and a second for children, both with the activeingredient ibuprofen. The infant formulation consists ofa concentrated liquid oral (50 mg per 1.25 mL)19 and isintended for infants aged up to 23 months. Children’sibuprofen is also an oral suspension. Its concentration is100 mg of active per 5 mL19 and it is intended for childrenbetween 2 and 11 years of age. Both products are supplied inbottles. Each product has a specific dosing device: a standardsyringe for the infant product and a thermoformed plasticcup for the children’s version.The user of either product is not likely to be the actualpatient. It may be a parent, a grandparent, a babysitter, ora healthcare professional. Designers will have to considerusers with different levels of education, and a broad rangeof abilities (i.e., perceptual, cognitive, and physical) andexperience.Varied contexts of use include different rooms of a house(e.g., bathroom, kid’s bedroom, kitchen, and so on) or evenan on-the-go situation (e.g., car, other house, a public place,etc). In the worst case scenarios, light might be inadequate,for example, because it’s late at night and parents simply donot want to awaken the child.Typical tasks include storing, identifying the correctproduct from among many, locating and understandingcorrect dosage information, opening child-resistant packages,dispensing and measuring by means of a dosing device,reclosing, and, eventually, disposal. The challenge is tosimultaneously consider the factors presented in the model inorder to optimise the likelihood of successful administrationof the product. For instance, locating and comprehending thecorrect dose might be particularly challenging for users notfamiliar with metric units or not formally trained regardingmedications, but may be readily understood by those whoare.If the dosing device is designed in such a fashion thatit is difficult to perceive (e.g. poor contrast, inadequate50 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Drug Delivery, Drug Packaging, Labelling & Dispensingembossing of units or text that is too small), mistakes couldbe made even if the care-giver thoroughly understandsthe dosing instructions. These difficulties can be furtherexacerbated by the context undergirding the interaction,such as the lighting of the environment and the condition,location and behaviour of the child, which have the potentialto add stress to the difficulty.A specific combination of events may conspire to confusethe user, inducing them to dose a child with the moreconcentrated infant product using the wrong dosing device,ultimately resulting in a medication error. For instance,different standard syringes might be available to the user,with no markings identifying their respective drug product.As such, a child could receive the right drug at the right dosebut in the wrong concentration because of an identificationproblem related to the packaging and dosing device.Inconsistencies in the measuring devices for children’sliquid oral dosages that are likely to lead to care-giverconfusion are documented. 10 In fact, largely as the result ofnumerous, documented, unintentional overdoses involvingliquid oral formulations, both the industry 20 and the US Foodand Drug Administration (FDA) have released guidancesregarding the inclusion, markings and abbreviationsappropriate to these devices. 21Epinephrine InjectionEpinephrine is generally administered parenterally; typicallyin the form of an injection used to treat life-threateningallergic reactions caused by insect bites, foods, medications,latex, and other causes. 22 It is packaged in varied forms,which include a single-dose pre-filled automatic injectiondevice that is applied in a “swing and stab motion” intothe thigh. Patients and their care-givers are instructed toadminister epinephrine at the early signs of a serious allergicreaction (as indicated by swelling redness, etc.).Users of epinephrine injections have a wide range ofabilities, as they include children to older adults, and the drugmay be self-administered or administered by a care-giver(e.g. healthcare professional, parent, teacher, babysitter,etc.). Care-givers, in particular, may or may not be familiarwith the appropriate use of the device that delivers the drug.Given the critical context of use (time is of the essence ina potentially life-threatening situation) and the variedexperience levels of those likely to administer the drug, clearand simple directions regarding this product are paramount.This product will always be used under a high level ofstress and rush induced by the emergency nature of theneed for it. Other characteristics of the context of use areincredibly varied and will likely include: outdoors, indoors,public places, homes, schools, vehicles, etc. A usage scenariocan be conjured for literally any place.The set of tasks include carrying the device (some usersmay actually “holster” this drug to themselves due to thetime-critical nature of its use), identifying the needle tip,removing its safety feature, holding the device in the rightposition, and administering the drug successfully (which inand of itself has a series of steps). These steps may lookeasy to replicate, but the combination of poorly designeddevices, untrained users, limited time for reasoning, and astressful context complicate the process, making clear andstraightforward design requisite for success, with potentiallife-threatening implications resulting from poor designs.ConclusionsA majority of efforts regarding the design and evaluationand drugs is devoted to understanding the chemical aspectsof the packaged product so that it is assured to be safe andefficacious throughout its stated shelf life. Yet, in virtuallyevery instance of healthcare, there are people (be they thepatient themselves or a care-giver – trained or untrained)who must interact with the packaged product such thatit is administered safely and effectively. As a result, thesafety of patients is partially dependent on a system ofphysical components such as packaging, measuring devices,www.JforPC.comJournal For Patient Compliance Strategies to enhance Health Outcomes 51

Drug Delivery, Drug Packaging, Labelling & Dispensingapplicators, dosing devices, closure systems, and the drugitself. 6 These components convey important informationregarding the safe and effective use of the products.The human-package interaction framework (presentedherein) indicates that any healthcare product has a setof intended users, a set of contexts of use, and a series ofspecific tasks that must be accomplished. The frameworkserves to support the design and evaluation of products in anattempt to reduce the occurrence of medications error andincrease adherence.References1. National Coordinating Council for Medication ErrorReporting and Prevention. About medication errors: Whatis a medication error? 2007; http://www.nccmerp.org/aboutMedErrors.html. Accessed March 16, 2011.2. Bates DW, Cullen DJ, Laird N, et al. Incidence of adversedrug events and potential adverse drug events. JAMA:The Journal of the American Medical Association.1995;274(1):29-34.3. Barber N. Should we consider non-compliance a medicalerror? Quality and Safety Health Care. 2002;11:81–84.4. US FDA. FDA 101: Medication Errors. 2009; http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048644.htm. Accessed March 18, 2011.5. DeWalt DA. Ensuring safe and effective use of medicationand health care. JAMA: The Journal of the AmericanMedical Association. 2010;304(23):Published onlineNovember 30, 2010.6. Ward J, Buckle P, Clarkson JP. Designing packaging tosupport the safe use of medicines at home. AppliedErgonomics. 2010;41(5):682-694.7. Food and Drug Administration. Guidance for industry.Dosage delivery devices for OTC liquid drug products.November, 2009; http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM188992.pdf. Accessed December 6, 2010.8. Berman A. Reducing medication errors through naming,labeling, and packaging. Journal of Medical Systems.2004;28(1):9-29.9. McCoy LK. Look-alike, sound-alike drugs review: includelook-alike packaging as an additional safety check. JointCommission Journal on Quality and Patient Safety.2005;31(1):47-53.10. Yin HS, Wolf MS, Dreyer BP, Sanders LM, Parker RM.Evaluation of consistency in dosing directions andmeasuring devices for pediatric nonprescription liquidmedications. JAMA: The Journal of the American MedicalAssociation. 2010;304(23):Published online November30, 2010.11. Kenagy JW, Stein GC. Naming, labeling, and packagingof pharmaceuticals. American Journal of Health-SystemPharmacy. 2001;58(21):2033.12. Lambert BL, Lin SJ, Chang KY, Gandhi SK. Similarity as arisk factor in drug-name confusion errors: the look-alike(orthographic) and sound-alike (phonetic) model. MedicalCare. 1999;37(12):1214-1225.13. US Pharmacopeia. Look-alike/sound-alike drug productsaffect cognition. 2004; http://www.usp.org/pdf/EN/patientSafety/capsLink2004-05-01.pdf. AccessedDecember 21, 2010.14. de la Fuente J. The use of a universal design methodologyfor developing child resistant drug packaging. EastLansing: School of Packaging, Michigan State University;2006.15. Card SK, Moran TP, Newell A. The psychology of humancomputerinteraction. Mahwah: Lawrence ErlbaumAssociates, Inc.; 1983.16. Shackel B. Usability - Context, framework, definition,design and evaluation. Interacting with Computers.2009;21(5-6):339-346.17. Monk A. Cyclic interaction: a unitary approach to intention,action and the environment. Cognition. 1998;68(2):95-110.18. Norman DA. The psychology of everyday things. New York,NY, USA: Basic Books.; 1988.19. All about kids Pediatrics. Ibuprofen dosage. 2011; http://www.allaboutkidspediatrics.com/parents/dosage.html.Accessed March 19, 2011.20. Consumer Healthcare Products Association. GuidelineVolumetric Measures for Dosing of Over-the-CounterLiquid Oral Drug Products for Children ≤ 12 Years ofAge. 2010; http://www.chpa-info.org/scienceregulatory/Voluntary_Codes.aspx#volumetricmeasure. AccessedMarch 21, 2011.21. US Department of Health and Human Services US Foodand Drug Administration. Guidance for Industry: DosageDelivery Devices for OTC Liquid Drug Products. In: (CDER)CfDEaR, ed2009.22. PubMed Health. Epinephrine Injection. 2008; http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000211/.Accessed March 19, 2011.Javier de la FuenteJavier is co-director of Factor IDD, adesign consulting company specializingin packaging and product design. He ispursuing a doctorate at the MichiganState University School of Packaging.His current research focuses on usabilityissues of flexible packaging. He earned his Master of Sciencedegree from the same school and holds a five-year degreein Industrial Design from the University of Buenos Aires,Argentina. Email: cjd@msu.eduLaura Bix, Ph.D.Dr. Bix is an Associate Professor at theSchool of Packaging at Michigan StateUniversity. She was appointed, andcurrently serves as the US delegateto ISO TC122 WG 9, a group which isdeveloping a standard for measuringthe accessibility of packages. Bix served as the Vice-Chairof Committee D10.32, the Committee on Consumer,Pharmaceutical and Medical Packaging, from 2004-2007, andas a member of Committee F-02, the flexible barrier materialcommittee, from 2002-2008. In 2008 she was named one ofthe 100 most notable people in the medical device industry byMedical Devices and Diagnostics Industry.Email: bixlaura@anr.msu.edu52 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

Drug Delivery, Drug Packaging, Labelling & Dispensingwww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 53

JOURNAL FORPATIENT COMPLIANCE✓Strategies to enhance Adherence and Health OutcomesPharma patient adherence budgets have increased 281percent in four yearsPatient adherence is a hot topic for the healthcare industrybecause it can impede or undermine patients’ recovery or achronic condition. Non adherence costs an estimated $290billion in hospitalization stemming from complications. Forthe pharmaceutical industry, improving it could provide away to save millions in lost revenue. An effective plan by apharmaceutical company could pave the way to a favorablespot on a formulary.As startups, providers and pharmaceutical firmsdevelop ways to solve this critical problem, a new reporthas highlighted some interesting trends. Pharmaceuticalcompanies are devoting more budget spend to patientadherence teams and allocations to digital programs havespiked in the past year.In the past four years US pharmaceutical companies’patient adherence budget allocations have jumped 281percent from $400,000 in 2009 to $1.5 million in 2012.But more importantly there is an increasing recognitionthat understanding patients and their motivations will helppharmaceutical companies better engage them and makeadherence programs more successful. Here are some of themost interesting findings in a patient adherence survey byCutting Edge Information in Durham, North Carolina.JCS – Staff Writer – Maria AlvarezPatient Portals – From Doctor to PatientWith the advent of social media platforms such asFacebook and Twitter, a tremendous hype was generatedby being in constant touch with one another. By virtueof this phenomenon, staying in touch round the clockvia instant messaging where any physical boundariesor restrictions were absent became the new norm. Thissimple and effective means of communication delivereda great value for all business entities alike. The absenceof employing such useful technology would project anegative image into the mind of your clients. Health ITvendors could not afford to lose in this department; hence,to provide a solution to this predicament patient portalsemerged. Through the introduction of patient portals byestablished EMR vendors, hassle for patients along withphysicians was significantly reduced.’Patient Portals provide a platform for patients to stayconnected with their providers. Instantaneous access toall the patients’ reports, scheduling appointments etc. hasmade life easy for patients comprehensively. These portalseliminate the requirement for making phone calls everytime a patient might have a health related query. It wasnever as simplistic to manage your patients’ health priorto patient portals’, says an Ohio based physician.For the healthcare industry today, the Patient Portalhas emerged as the definitive platform for better patientengagement. The technology is so simplistic in nature thatpatients find it very user friendly to utilize and can operateit almost immediately with little or no training. All anypatient has to do is simply login to the online web basedportal in order to remain connected with their doctor.They can do this from any place and at any time;needless to say that this freedom of mobility ensued innumerous benefits. Now both patients and doctors didn’thave to incur the unnecessary costs on lengthy phone callsto one another. Reports could be obtained online, alongsideother relevant medical information. Even requesting refillsand scheduling appointments was made simple, at theconvenience of just a few clicks away.Source: Cutting EdgeOnline survey on the management of patient adherenceResearchers at Keele University have launched an onlinesurvey to learn about health care professionals’ (doctors,pharmacists and nurses) approach to supporting patientswith taking medicines and promoting adherence.Dr Wendy Clyne and colleagues at NPC Plus, KeeleUniversity, are coordinating the survey which is part ofa larger project on medicines adherence called the ‘ABCproject’ (www.abcproject.eu/) funded by the EuropeanCommission. The survey is taking place in countries acrossEurope including Austria, Belgium, France, Germany,Greece, Hungary, Italy, Portugal, Poland, Switzerland, TheNetherlands and England. The survey will run until the endof March 2012.The survey aims to investigate health care professionals’perceptions of the extent and nature of non-adherence,as well as the things that health care professionals do tosupport patients with medication taking.54 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4

JPC NewsThe study also aims to find out about any barriers tosupporting adherence as reported by doctors, pharmacistsand nurses. Dr Clyne, Head of the Medicines PartnershipProgramme at NPC Plus, said ‘With more patients takingmedicines than ever before, encouraging patients toget the most out of their medicines is essential to avoidunnecessary ill health as well as reduce waste andunnecessary cost. We are really interested to find outwhat healthcare professionals do to support patients withmedicine taking, and how effective they think their actionsare. At the end of the study we should have a really clearpicture of the role of these three key professional groups insupporting patients with medicines, how that support fitstogether, and whether we have a consistent picture acrossEurope, or whether there are variations in practice fromone country to another.’Source: Cutting EdgePatient adherence predicts ankle surgery healingFocusing on postoperative care may be the optimal wayof reducing healing complications following ankle fracturesurgery, say US researchers.The team from the Thomas Jefferson UniversityHospital in Philadelphia, Pennsylvania, reports thatsurgical debridement was required by just six (1.25%) of478 patients who underwent open ankle reduction andinternal fixation between 2003 and 2010. A further 14(2.9%) patients needed additional wound dressing or oralantibiotics during healing.Nevertheless, multivariate analysis identified several riskfactors for postoperative wound complications among thispopulation.Specifically, patients were significantly more likely tohave wound complications if they had diabetes (odds ratio[OR]=3.61) or an open fracture (OR=13.43), and if theyused wound-compromising medications (OR=6.75), such ascorticosteroids.Furthermore, delayed wound healing was a significant3.66 times more common in patients who were nonadherentto postoperative instructions, such as avoidance of weightbearing for at least 6 weeks, compared with patients whofollowed their physician’s advice.The risk for wound complications also rose significantlywith increasing patient age, say Adam Miller and co-authors.“While most risk factors cannot be controlled,postoperative care is an area of importance for woundhealing,”writes the team. “The adherence to postoperativeinstructions should be emphasized, and the treatingsurgeon should remain vigilant to the potential effect thatnoncompliance may have on wound-healing after surgicalintervention.”The researchers note in the US edition of the Journalof Bone and Joint Surgery that there was a trend towardan increased risk for wound complications in patients whounderwent surgery within 5 days of injury compared with ata later date, but that this did not reach significance.They were also unable to demonstrate any impact ofpreoperative swelling on the risk for wound complicationsin their study due to the subjective nature of the analysis.Believing these two factors may nevertheless havesignificance in wound healing, they add: “This conjectureneeds to be confirmed in a future randomized comparativestudy.”JCS – Staff Writer – Maria AlvarezAttitudes Predict Ability To Follow Post-Treatment AdviceWomen are more likely to follow experts’ advice on how toreduce their risk of an important side effect of breast cancersurgery - like lymphedema - if they feel confident in theirabilities and know how to manage stress, according to newresearch from Fox Chase Cancer Center presented at the2012 CTRC-AACR San Antonio Breast Cancer Symposiumon Saturday, December 8, 2012.These findings suggest that clinicians must do morethan just inform women of the ways they should changetheir behavior, says Suzanne M. Miller, PhD, Professor andDirector of the Psychosocial and Biobehavioral MedicineProgram at Fox Chase and study author. Doctors and nursesshould also provide strategies for women who feel lessempowered to make those changes, and have fewer skillsfor reducing their stress.“Women are in charge of their future, because there arethings they can do to minimize the effects of treatment,”says Miller. “If they get into a routine of doing them, it willreduce their stress and vulnerability.”The study, funded by the U.S. Department of Defense,focused on the side effect of surgery known as lymphedema- an incurable build up of fluid in the lymph nodes that cancause swelling and affect range of motion. In more severecases, it can be quite painful. The rate of lymphedema canvary, but a significant proportion - perhaps as many ashalf - of women will develop it after undergoing surgery toremove breast cancer.“That advice may sound easy to follow, but the realityis quite different,” says Miller. To truly follow theserecommendations, she says, women have to forever changeand monitor their behavior - moisturize the arm on the side ofsurgery several times per day, use an electric shaver insteadof a razor, wear gloves when doing housework or physicalactivity, avoid tight jewelry or clothes, stop carrying heavyobjects, and constantly protect the arm from being jostledor squeezed, for instance. “These changes are going to bevery intrusive into a woman’s everyday life,” says Miller.Source: NHS Health Newswww.JforPC.comJournal For Patient Compliance Strategies to enhance Adherence and Health Outcomes 55

Drug Delivery, Drug Packaging, Labelling & DispensingJOURNAL FORPATIENT COMPLIANCE✓Strategies to enhance Adherence and Health OutcomesAdvertisers IndexPage 29 9th Annual Patient Summit Europe 2012 - EyeforPharmaPage 33 10th Annual Conference on Controlled ReleasePage 53 11th Annual Eyeforpharma Barcelona 2013Page 390 Ten HealthcareIFCAtlantis HealthcarePage 23 BobstPage 38 & 39 CRF HealthIBCHealth WindowPage 11 MemotextOBCMediciGlobalPage 19 Mobile PRMPage 47 Patient Summit USA 2013Page 7PCC HellasPage 27 Pharma PublicationsPage 5PharmexxPage 15 Vitaphone Nederland BVSubscription offerGuarantee you receive your copy of JPC:4 issues per year. Pharma Publications is delighted to be ableto offer it’s readers a great one year’s subscription offer.Subscribe now to receive your 20% discountPost: Complete form below, detach and post to:Pharma Publications, Unit J413, The Biscuit FactoryTower Bridge business complex100 clements road, London SE16 4DGTel: +44 (0)20 7237 2036Fax: Complete and fax this form to +44 0014802475316Email: Your details to info@pharmapubs.comPlease tick the relevant boxes below:Card numberValid fromSecurity codeName:Job title:Company:Address:Expiry dateUK & N. Ireland £120 inc p&pEurope €130 inc p&pUSA $200 inc p&pI enclose a cheque made payable to PharmapubsI wish to pay by credit card (Mastercard or Visa)Tel:Fax:Email:SignaturePostcode56 Journal For Patient Compliance Strategies to enhance Adherence and Health OutcomesVolume 2 - Issue 4