Combining health and social protection measures to reach the ultra ...

Access to healthAmericans think that the pharmaceutical industry is doing agood job, on par with their view of the tobacco industry 17 . Trialregistration can be seen as part of a crucial effort to restorepublic trust in medical research 18 . It constitutes a publicinvitation for further scrutiny and control of publication ofresearch results and as a statement that when it comes topatient and consumer safety, nothing ought to remain hiddenbehind a veil of corporate or governmental secrecy.Mandatory registration can also be connected to establishedmoral obligations to research subjects. Research participationis valued by participants as a public service 19 . They expect thatthe information gathered through their assistance contributesto scientific progress. This is why influential research ethicsguidelines or statements such as the Declaration of Helsinki 20and the Nuremberg Code 21 both require that the design andpurpose of studies on humans be publicly available and thatthe rights of trial participants take precedence over bothcommercial and career interests 22 . As noted by the ICMJE,research participants “deserve to know that the informationthat accrues from their altruism is part of the public record,where it is available to guide decisions about patient care, anddeserve to know that decisions about their care rest on all ofthe evidence, not just the trials that authors decided to reportand that journal editors decided to publish” 23 . Assuringresearch subjects that their participation provides a publicbenefit should also stimulate their commitmenttowards research 24 .Registration further promotes knowledge transfer.Discrepancies between information gathered in clinical trialsand reported results have long been recognized 25 . Mandatoryregistration enhances dissemination of important clinicalinformation among clinicians, researchers, governmentalagencies, and the public. It improves information exchanges,for example, between industry-based and academicresearchers and alerts researchers to gaps in the knowledgebase 26 . It facilitates knowledge creation and knowledgetransfer within the drug development and innovation sector 27and enables “research into research”, both from a clinicalperspective and a science and technology studies perspective 28 .From a regulatory perspective, the most importantcontribution of mandatory registration is that it allows theresearch community and governmental agencies to bettercontrol for bias in clinical trial design and publication 29 . Designbias occurs when a trial is designed with a high likelihood ofbeing positive, for example through careful selection of clinicaltrial populations. Publication bias refers to the practicewhereby studies providing unfavourable or negative result arenot published or misrepresented through data selection. Biascan occur because journals are less interested in publishingnegative research outcomes. As various controversieshighlight, it can also be part of a commercial strategy to hideresults that will not support an application for new drugapproval or that will undermine the efficacy or safety status ofan existing product 30 . Clinical trial registration allows theresearch community to scrutinize what studies have beenproposed, whether the design seems appropriate, how manypatients were being recruited, what the intended outcomeswere, and whether the studies seem fully reported.Mandatory registration can also contribute to scientific andeconomic efficiencies in clinical research. It may reduce riskto research subjects by avoiding unnecessary duplication ofefforts and minimizing situations where harm to subjects hasnot yet been reported 31 , while also encouraging appropriatereplication and confirmation of results 32 . On a global level,public disclosure of the existence of certain trials fosters bothinternational collaboration among researchers and recruitmentto clinical trials which serves to enhance trial success rate 33 .Interestingly, at one of WHO Clinical Trials Platform meetings,patient advocates also suggested that an international centralregistry will promote trial participation, by providinginformation for patients who would often be willing to travel toparticipate in clinical trials. Finally, registration should helpdomestic and international funding bodies target resourceswhere they are most needed and likely to be effective 34 . Wellcoordinatedglobal registration will further help domesticgovernments, particularly those in resource-poor countrieswith less mature regulatory regimes to better manage andmonitor their clinical research programmes and protectvulnerable trial populations 35 .Promoting public trust, transparency of research andknowledge transfer, respecting research subjects, andfacilitating clinical trials thus provide the underlying rationalefor registration. It seems clear that meaningful, i.e. substantialdisclosure, corresponds most with these values. Any exceptionto the principle of extensive disclosure of research informationought therefore to be justified by considerations that areequally pressing. What are the concerns about mandatoryregistration and do they trump the public interest in trialregistration?Registration, intellectual property rights andcompetitive interestsPatent concernsThe argument that public disclosure of the informationrequested in WHO clinical trials platform will undermine apotential patent application seems weak. When a novelproduct or “novel use” of a product is tested in clinical trials, itis usually already protected by a patent. Patent applicationsare filed as soon as there is an expectation that a newcompound or a new use may be patentable subject matter. Fora new product, this generally occurs early on in thedevelopment process, years before a clinical trial isundertaken. For a new use patent, an application would befiled as soon as there is a realistic expectation that this newuse is patentable, again long before it is tested in a clinical trial.In fact, the existence of patent protection for new productsand new uses undermines the arguments against detailedregistration and disclosure requirements. Patent applicationsoften contain more information about potential drugdevelopment strategies than the summary informationrequired for registration under the current WHO Platformproposal. They will be published in most jurisdictions within18 months of the application. Domestic patent legislation inseveral jurisdictions, as well as the 1970 Patent CooperationTreaty 36 , explicitly require publication of the patent applicationwithin a short period of time after registration of the patent.Global Forum Update on Research for Health Volume 4 ✜ 041