American Journal of Law & Medicine

Access to information and the right to health: the human rights case for clinical trials transparency.

 CONTENTS   I. INTRODUCTION  II. CLINICAL TRIALS REGISTRATION AND RESULTS REPORTING      IN CONTEXT      A. Early History      B. International Developments      C. National Implementation      D. Remaining Challenges         1. Enforcement and Implementation         2. Scope of Trial Registration Requirements and Inclusion           of Results Reporting         3. Halting of Progress? III. POTENTIAL CONCERNS RELATED TO TRIAL REGISTRATION AND      RESULTS REPORTING      A. Costs and Administrative Burden      B. Risks of Misinterpretation      C. Patent Concerns      D. Data Secrecy and Competitive Advantage  IV. LOSS OF REGULATORY DATA PROTECTION: TRIPS AND      DATA PROTECTION      A. Article 39 of TRIPS and Data Protection      B. The "Protection Against Unfair Commercial Use" Exception      C. The Public Interest Exception      D. Public Interest Approaches: The Right to Health and         Clinical Trials Data as a Public Good   V. HOW IMPORTANT ARE TRIAL REGISTRATION AND      RESULTS REPORTING?      A. Goals of Trial Registration and Results Reporting         1. Patient and Consumer Empowerment and            Promotion of Collaboration         2. Reducing Bias      B. Public Health Challenges Resulting from Biased Research      C. How Effective Will Clinical Trials Registration and Results         Reporting Be in Addressing the Problems?      D. Are Current Registration and Results Reporting         Practices Sufficient?  VI. THE RIGHT TO INFORMATION AND THE RIGHT TO HEALTH      A. The Right to Information as a Critical Determinant of         the Right to Health         1. The International Human Right to Health         2. Access to Information         3. Access to Information about Medicines as a            Determinant of the Right to Health      B. Countering Industry Arguments: Human Rights and Access         to Information as Interpretive Tools      C. Obligations Imposed by Recognition of Fundamental         Human Rights      D. Drawbacks and Challenges to a Human Rights Approach VII. CONCLUSION 


Access to medicine remains a core challenge of global health, despite progress in bringing affordable HIV/AIDS drugs to developing countries. Yet, the debate seems to have shifted. For a long time it focused on two specific issues: (1) whether and to what extent international trade agreements that strengthen patent protection hindered states and NGOs in their efforts to promote access to life-saving medicines at reasonable costs; and (2) whether access to life-saving therapies could be seen as a component of the right to health. The challenge for access to medicines appears at this point, however, to be more political than legal. (1) Indeed, from a legal perspective, it seems fairly settled that international trade agreements permit, under certain conditions, the production and sale or export of generic versions of pharmaceutical products that address an important public health threat in developing countries. (2) The concept of the right to health has often been invoked in this international context. An increasing number of domestic court decisions also explicitly acknowledge that access to life-saving therapies can be seen as a component of the right to health. (3)

In contrast, the discourse around international trade agreements and human rights has largely ignored the serious health implications of data secrecy. While there is a growing consensus on the human rights dimension of access to life-saving therapies, discussions about the need to have access to reliable information about the safety and effectiveness of those medical therapies, particularly pharmaceuticals and medical devices, remains underdeveloped. Even though some policy papers have recognized the importance of access to data from a consumer perspective, (4) the topic has received little to no attention in analyses of the human rights and public health implications of international trade agreements such as the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) and related bilateral trade agreements. (5) This lack of attention is to some extent understandable. Pharmaceutical products must first be available and affordable for the lack of reliable information about those products to become a matter of public health concern. Yet the importance of access to reliable information about the efficacy and safety of therapeutics should not be lost in the debate over the need to improve access. Promoting access without attention to the need for reliable information may undermine gains made in public health. Aggressive promotion of therapeutic products can result in a waste of scarce resources and public health challenges associated with improper prescription and overconsumption of medication, which would disproportionally affect developing and semi-industrialized countries. This is, as we will discuss further, already a serious public health challenge in industrialized countries.

In this Article, we argue that access to information about clinical trials, which is a crucial tool for drug and medical device development, ought to be recognized as a fundamental component of the right to health. In the context of reproductive rights, the right to information has already been convincingly linked to the right to health. In that context, the argument has been made that women can only exercise their right to reproductive health services, such as abortion or birth control, if they also obtain information about these services. (6) Admittedly, the relationship between the right to health and access to information in the reproductive rights context may seem more direct. Protection of the physical and mental integrity of women, thereby promoting their healthcare empowerment, clearly requires immediate access to information about reproductive health services. We argue, nevertheless, that there is also an undeniable link between access to clinical trials information and the right to health and that this should be used to promote the establishment of solid knowledge systems based on transparent data. (7) This Article aims to show how this human rights discourse about the need for complex information systems can help curtail TRIPS-based arguments about the duty of states to protect data secrecy.

This human rights-based claim is compatible with the view proffered by some legal scholars that clinical trials data are a public good and should be organized by the state, (8) a claim made also in the health policy literature. (9) We argue in this Article that situating access to information within the context of the right to health is not only reconcilable with this approach, but offers distinct advantages, particularly in the absence of fundamental reform of the clinical trials industry.

The lack of attention to the issue of access to reliable pharmaceutical information in health and human rights debates contrasts with the considerable debate in the medical and health policy literature. Various important initiatives have also been undertaken to promote transparency and access to safety and effectiveness data of clinical trials, in particular, through the creation of trial registration and results reporting obligations. (10) Yet these initiatives rely largely on the goodwill and collaboration of research sponsors and of those involved in conducting clinical trials. (11) Most countries have neither a strong regulatory framework nor the legal or theoretical foundation for the duty to provide access to information about therapeutic products. There is also no coherent recognition of the crucial importance of access to clinical trials data. More importantly, international trade agreements are still invoked as an impediment to promoting the transparency of clinical trials data. Initiatives to promote clinical trials registration and results reporting are diverse and not always coherent. Moreover, notwithstanding various initiatives over the last decade, the momentum in favour of full transparency may be disappearing. (12) In this Article, we will first describe the historical developments of these initiatives. We will then explore some of the objections against trial registration and results reporting, focusing in particular on the international trade-related objections. These objections will be countered and contrasted with the public health importance of trial registration of results reporting. This will allow us to discuss in more detail why access to information about clinical trials can be seen as a component of the right to health. This Article will conclude with a discussion of the possible implementation of human rights claims in relation to clinical trials transparency.



The idea of using trial registration to promote transparency of clinical research is not new. Starting in the 1960s, trial registries were set up for specific diseases. (13) Yet many of these early registries survived only briefly. Others contained information on only a small number of publicly funded clinical trials. Also, until recently, there was no attempt to gather information on the number or type of clinical trials undertaken worldwide. Kaye Dickersin and Drummond Rennie estimated in 2003 that of the probably more than one million clinical trials carried out since the 1950s, only about half had been publicly reported. (14)

Calls for the establishment of publicly accessible registries of clinical trials, (15) or even for one international registry, (16) became louder in the 1980s. Researchers argued that trials were needed to facilitate meta-analyses of both published and unpublished clinical trials. (17) Meta-analyses based on some of the existing disease registries had raised a red flag about the existence of a positive publication bias: the published literature would suggest that a particular treatment was effective, whereas an analysis of all the clinical trials conducted indicated the opposite. (18)

Interestingly, the first governmentally supported trial registries aimed more at promoting awareness about clinical trials for novel therapies in the context of life-threatening diseases. (19) They focused primarily on obtaining information about the type of disease, the experimental treatment, eligibility criteria, location, and contact information. (20) The first registry, the AIDS Clinical Trials Information System (ACTIS), was established in 1988 in response to demands from the HIV/AIDS community for better access to innovative therapies through clinical trials. (21) Nine years later, lobbying from the breast cancer community resulted in the establishment of a general "public resource" for information on clinical trials for serious and life-threatening diseases. (22) This database,, became publicly accessible in 2000 and is currently the largest clinical trials registry in the world. While these registries focused on promoting information about the trials to facilitate participation, they also reflected a growing recognition of the public interest in transparency.

As is often the case, powerful emotional triggers were needed to stimulate a public policy response. In this case, two controversies--one involving children, another involving a very high number of patients--created more general public awareness about the significant consequences of biased and unreliable reporting. The first controversy exposed a host of questionable research reporting and marketing practices of pharmaceutical giant GlaxoSmithKline (GSK) related to the use of its antidepressant Paxil for the treatment of depression in pediatric populations. (23) In 2004, the Attorney General of New York prosecuted the company for these practices, which allegedly involved hiding of negative data, selective publishing of positive data, and use of skewed publications to promote off-label prescriptions. (24) Another notorious controversy involved the pain relief medication Vioxx, which according to various estimates, may have resulted in hundreds of thousands of acute myocardial infarctions and cardiac deaths. (25) In the context of Vioxx, analyses of internal company documents also revealed a lack of reporting of data and the use of ghost-writing in scientific publications. (26)

These controversies erupted at the right time to create a momentum for transparency initiatives. Developments in computer technology, as well as the Internet, facilitated publicly accessible databases and exchange of information at a global level. Improved technology made it feasible and affordable, but the very public nature of these controversies, namely the fact that they involved hiding a serious risk to children in one case and hundreds of thousands of premature deaths in another, confirmed that public health was at stake.

As part of the settlement with New York's Attorney General, GSK also agreed to set up a publicly accessible registry of all of its clinical trials. (27) Thus, it became more difficult for industry to justify strong resistance based on alleged incompatibility of trial registration with normal business practice. Other companies followed suit. (28)


Although there have been some interesting earlier international initiatives, (29) it is only in the wake of these controversies that trial registration gained momentum internationally. In 2004, at a Global Forum and Ministerial Summit on Health Research in Mexico, delegates from fifty-two countries issued the Statement on Health Research in which they emphasized the need to promote access to evidence, and called upon the World Health Organization (WHO) to establish "a platform linking a network of international clinical trials registers to ensure a single point of access and the unambiguous identification of trials." (30)

In response, in 2005, the WHO established the International Clinical Trial Registry Platform (ICTRP), which coordinated the creation of international standards for registration of clinical trials. The ICTRP developed a search portal and a unique identifier numbering system and identified a set of key items (the minimal data set) to be entered into the registries. (31) Many supporters of trial registration, including the Ottawa Group--a group of international scientists associated with the Cochrane Collaboration that developed influential international consensus statements on trial registration and results reporting--argued that the ICTRP data set should have imposed registration of several other important clinical trials data. (32) Nevertheless, the WHO initiative generally was seen as an important step towards greater transparency, enabling at the least an unambiguous identification of all clinical trials through the creation of a unique numbering system and the registration of some key data. (33)

The need for trial registration and overall transparency of research was confirmed internationally at the Bamako Global Ministerial Forum on Health in 2008. Member organizations of the WHO have actively promoted the implementation of the ICTRP recommendations in the regions. The Pan American Health Organization (PAHO), for example, adopted a new PAHO Policy on Research for Health in 2008, which emphasizes the need for trial registration. (34) PAHO has also been instrumental in facilitating collaboration among various countries so that national registries of semi-developed and more populated countries could function as primary registries (35) for other countries in the region. (36) Efforts are underway to use the Brazilian trial registry as a PAHO supported registry for South America. (37) In March 2011, a Cuban registry established with support from PAHO and the ICTRP became the first primary registry for the ICTRP in a Spanish-speaking country. (38)

One other international initiative is also worth mentioning. In 2008, the World Medical Association's new version of the influential Declaration of Helsinki on Ethical Principles for Research Involving Human Subjects referred, for the first time, to the requirement to prospectively register every clinical trial. (39) It also specified that authors, editors, and publishers share ethical obligations related to the disclosure of research results, and identified authors as those who are ultimately responsible for appropriate publication of research results. (40)


At the national level, the United States was the first to introduce stringent registration and results reporting requirements through legislation. The 2007 FDA Amendment Act imposes a duty to register all Phase II to lV trials of pharmaceutical products submitted for drug regulatory approval and medical device trials, other than feasibility studies, with, and to report the results after finalization of the trial. (41) The European Commission also issued a communication indicating that all Phase II, III, and IV trials of medicinal products with at least one site in the European community have to be registered with the EuroPharm database, (42) which is set up by the European Medicines Agency (EMA). (43) Trial registration has also become mandatory in other countries such as Brazil, Argentina, (44) India, (45) and Japan, (46) through regulatory requirements of the ministries of health. South Africa has indicated its intention to do the same. (47) In other countries, trial registration and results reporting obligations have been introduced by the funding agencies through research ethics guidelines. (48)


1. Enforcement and Implementation

As described above, the progress made since 2004 is significant, but major challenges remain. The first is that comprehensive implementation and enforcement of standards is difficult in a globalized research context. Although most of the world's clinical trials focus on product development for the industrialized world, in particular the United States, Europe, and Japan, the clinical trials business itself is increasingly global. The number of trial sites outside the United States has more than doubled in the last ten years. (49) India, Brazil, Russia, and China have been identified as new powerhouses of the clinical trials industry, estimated to be worth fifty billion dollars. (50) The growth in the number of registrations of clinical trials taking place worldwide is impressive, including in many developing countries and regions, (51) but compliance with the WHO-supported call for universal registration is far from assured.

The ICTRP system is dependent on national and regional implementation. It is not itself a registry, but provides a unique identifier (a universal trial number) to clinical trials that are registered in primary registries. (52) The system is key in avoiding fragmentation since the rapid development of trial registries risked resulting in a plethora of disease-specific, national, and regional registries with different purposes, different data requirements, different coding of data, different levels of detail, different software, and so on, which would make comparisons very difficult. Yet the ICTRP has no enforcement mechanism. Enforcement has to take place at the national level. At the WHO Bamako Global Health Forum, governments were therefore urged "[t]o develop, set, and enforce standards, regulations, and best practices for fair, accountable, and transparent research processes, including those related to ... the registration and results reporting of clinical trials and open and equitable access to research data." (53) Unfortunately, only a few countries have equipped trial registration systems with strong regulatory force. (54) As previously mentioned, other countries commit to trial registration in research ethics guidelines or clinical practice standards, but these approaches often fail to provide good enforcement mechanisms. (55)

First, funding agency guidelines normally bind only researchers or institutions receiving governmental funding. The sanction in case of non-compliance is withdrawal of funding, which is imposed on the researchers or the institutions receiving funding, not on the industry sponsors. Moreover, most pharmaceutical and medical device trials take place in contract research organizations (CROs), thus outside of federal institutions receiving federal funding. CROs are not bound by funding agency guidelines.

Second, practice standards rely on the goodwill and collaboration of industry. If the practice standards are not attached to a stringent regulatory requirement and active monitoring by regulatory agencies, compliance is hard to achieve. (56) This is particularly true if there are significant financial incentives to avoid registration and results reporting. The history of provides evidence that absent firm enforcement mechanisms, compliance remains limited. The 1997 FDA Modernization Act required that all trials for serious and life-threatening diseases be registered on, but it largely relied on the Food and Drug Administration's (FDA) issuing of more detailed guidance documents and discussions with industry to finalize the registration requirements. (57) The 1997 FDA Modernization Act failed to define serious and life-threatening diseases, thus leaving room for interpretation, and lacked regulatory sanctions. As a result, regulatory compliance was dismal. In 2005, a report concluded that only thirty-five percent of industry-sponsored studies that fulfilled the criteria for registration were actually registered. (58) Other analyses found that information crucial to making the registration meaningful was missing for many registered trials, particularly industry-sponsored trials. (59)

A recent article in the British Medical Journal also indicates how transparency policies without stringent enforcement rules will be insufficient. The article reports the difficulties researchers of the Danish Cochrane Centre encountered when trying to obtain access to the unpublished data of Phase II clinical trials of two weight loss drugs that had been approved by the EMA, but that had been associated with serious adverse events. (60) It took more than two years of mediation by the European Parliament's ombudsman and public criticism to get access to the data, even though public health interests clearly supported the request for access. (61)

Drummond Rennie concludes from the failure that "a central register cannot work unless it is designed to include all trials ..., is adequately funded, is made mandatory, is adequately policed, has substantial penalties for noncompliance, and unless all aspects of the enterprise are taken out of the hands of the pharmaceutical industry." (62)

The penalties included in the 2007 FDA Amendment Act certainly suggest that the U.S. legislature took its lessons from history. It introduced severe penalties for non-compliance: withholding of funding for those who are federally funded, financial penalties for non-compliance of $10,000 per violation per day, and posting of notices of non-compliance in the registry and the results database. (63)

2. Scope of Trial Registration Requirements and Inclusion of Results Reporting

A second challenge is the scope of the registration and results reporting requirements. The FDA Amendment Act, which introduced the most comprehensive legal requirements, does not require registration of all clinical trials: most Phase I trials of pharmaceuticals and feasibility trials for medical devices are excluded. (64) The European Union system requires registration of all clinical trials in its EudraCT database, but this database is only accessible to the regulatory authorities of the member states. (65) Its publicly accessible database EudraPharm, which the European Commission launched in March 2011, also excludes information on Phase I trials and certain information about clinical trials design and clinical trials sites. (66)

3. Halting of Progress?

Finally, the most worrisome challenge is that the process towards greater transparency seems to have stalled. The global introduction of trial registration and the creation of universal trial numbers were never perceived as being able to solve all problems associated with clinical trials transparency. Many experts felt that the ICTRP minimal data set was too limited and that more information was needed to enable meaningful analysis of clinical trials. (67) International trial registration was seen as an achievable first step. Industry had already mounted strong opposition to the public registration of several inputs into the ICTRP minimal data set. Insisting on other measures, such as providing access to the full protocol, to all amendments during the trial, to final results, and even to the raw data generated in a clinical trial, arguably could have derailed the process towards full transparency before it was fully underway because it could possibly have faced such strong opposition. (68) Incremental changes are often easier to digest.

The plan to use registration as a stepping stone for further transparency is apparent from the WHO's establishment of the Working Group on the Reporting of the Results of Clinical Trials. This working group published a discussion paper, proposing that "the findings of all clinical trials must be made publicly available." (69) This one sentence proposal is still available on the WHO ICTRP web site, as well as the revealing statement: "As there is no formal consensus on international norms and standards for reporting the findings of clinical trials, a working group was established to advise the ICTRP on this issue." (70) No further significant progress appears to have been made towards implementing a results reporting requirement.

In the context of a major reorganization and budget cuts within WHO, the ICTRP office in Geneva was also significantly reduced, with the removal of key personnel. The "ICTRP team" now consists of a Geneva-based coordinator and information technology officer, and five regional officers. (71) Dr. Charlotte Bouesseau, the new ICTRP coordinator, confirmed that the WHO remains "strongly committed to maintaining this effort [to improve transparency in research], which includes the promotion of results reporting." (72) It is to be feared, however, that as a result of the budget cuts and the reduction in personnel, the ICTRP now may be focusing more on the consolidation and the promotion of clinical trials registration, and that the implementation of an international results reporting system will not happen in the near future.

Another concern is that some countries with significant pharmaceutical product development fail to implement solid transparency measures. In 2011, Canada's Auditor General, for example, urged Health Canada, the country's drug regulatory agency, to "fulfill long-standing commitments to enhance public access to information on authorized clinical trials." (73) The agency responded by indicating its intention to introduce policies that will "respect legislation." (74) Yet, Health Canada has been very restrictive in its interpretation of existing access to information legislation that would already allow the agency to provide public access to clinical trials data on the basis of a public health interest. (75) It clearly seems to drag its feet with the implementation of strict registration and results reporting requirements. Since 2007, it has indicated that it would implement a coherent policy, (76) yet has so far only issued an official notice, "encouraging" trial registration and results reporting. (77) At the same time, the Canadian Institutes of Health Research (CIHR), the flagship agency for funding of biomedical research, recently withdrew an internationally respected transparency policy that imposed strict registration and results reporting requirements just three months after making it publicly available. (78) The official reason was that a new version of the Tri-Council Policy Statement, a research ethics policy that applies to research undertaken in all federally funded institutions, now contains registration and results reporting requirements. (79) These requirements, however, are much more vague and are implemented and controlled at the institutional level by local research ethics boards rather than by the funding agencies. The CIHR president expressed, in response to international criticism, CIHR's continued commitment to transparency. (80) Yet, the agency has since laid off one of its senior advisors who has been a key national and international promoter of trial registration and results reporting. (81) Corporate realignment and budget cuts are the official reason to reorganize the knowledge translation unit, but it is an interesting coincidence that all this is happening at a time when the agency is aggressively promoting closer collaboration with industry, particularly in the context of clinical trials and pharmaceutical product development.


Although industry has voiced its lukewarm support for some transparency measures, (82) it has opposed more detailed trial registration obligations and the expansion towards results reporting. Improved recruitment of research subjects is cited as a benefit by industry, (83) but the need to restore credibility and public trust clearly seems to be the primary reason for industry support of trial registration. (84) Nevertheless, industry interests remain the main stumbling block to detailed prospective trial registration and, even more so, results reporting. …

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