Clinical Trials

❘❙❚■ Chapter 5 | Patient SelectionIt might also be necessary to consider what effect previous treatments might haveor to actually withdraw a treatment (washout period) before starting the treatmentunder investigation. Depending on the length of time a drug stays in the body,a specific washout period may need to be defined. For example in CHARM,a period of 2 weeks for drugs similar to candesartan was specified [1].Selecting patients who have not been treated previously is a common requirement,as previous therapies can mask or reduce the effect of the treatment underinvestigation. However, in some chronic diseases (eg, asthma) this will be impractical.With other studies, withholding treatment can be unethical (eg, in Alzheimer’sdisease or cancer). In these studies, unequal numbers are often allocated to thetreatment and control arms (eg, in a 2:1 ratio) to move quickly and to gain patientexperience with the new drug [2].Ethical issuesAs mentioned previously, it is important not to make the eligibility criteria toostringent, otherwise there may be difficulty in enrolling sufficient patients – abalance needs to be achieved between scientific and practical issues. For example,individuals aged >65 years are frequently excluded from clinical trials becausethey are more likely to be taking concomitant medications and might be lessresponsive to treatment, more affected by side-effects, and/or more difficult toevaluate. However, if the treatment or intervention under investigation isintended to be used in clinical practice by individuals in this age group then theyshould be included.Special consideration should be given to children or neonates as they can respondto medications differently to adults. A report by the EU revealed that >50% ofmedicines used in children have not have been adequately studied in this agegroup [3]; consequently, the EU is developing legislation that will require data onchildren to form part of the authorization application for medicines that are to beused in children.There are other ethical issues to consider when selecting patients for studyinclusion. For example: repeat visits or tests might be onerous for patients; testscan be painful or uncomfortable; the study might require the patient to take timeoff from work or school; and the study will often require patients to wait inhospital for tests or for the study drug to be issued from the pharmacy.52