Clinical Trial Disclosure Research Articles

Clinical trial transparency and disclosure from the medical writing perspective

It’s been more than 6 years since our last Medical Writing edition dedicated to clinical trial transparency and disclosure. Since then, we have seen the full implementation of the long-awaited EU Clinical Trials Regulation (CTR), the pause and restart of EMA Policy 0070, and of course a global pandemic which resulted in a world-wide surge in freedom of information requests for Covid-19 vaccine clinical trial data. Although many of the regulations and policies governing public disclosure of clinical trial data and documents remain unchanged, we have seen significant changes in the way these are implemented. As those of us who work in this field know all too well, the landscape is ever changing, and it is essential to keep up to date with those changes. Resources such as the Drug Information Association Clinical Trial Disclosure Community, PHUSE Data Transparency Working Group, and Clarity and Openness in Reporting-E3 based (CORE) Reference provide invaluable updates and insights. This issue of Medical Writing touches on a number of different aspects of clinical trial transparency and disclosure, all of which involve medical writers as key stakeholders

Current clinical trial disclosure landscape in Asia

The transparency and disclosure landscape in Asia has been rapidly evolving during the past decade. With respect to clinical trial registries, China launched its national registry, ChinaDrugTrials.org.cn, in 2013; South Korea introduced the new clinical trial disclosure platform through its Ministry of Food and Drug Safety (MFDS) in 2019; whilst Japan unified its three existing primary registries into a single clinical trial registry – Japan Registry of Clinical Trials (jRCT) – in 2020. We provide an overview of the national clinical trial registries and the trial results disclosure practices for 4 Asian countries – China, Japan, South Korea, and Taiwan.

Trends of clinical trials from 2017 to 2019 in Korea: an integrated analysis based on the Ministry of Food and Drug Safety (MFDS) and the Clinical Research Information Service (CRIS) registries.

Public disclosure of approved clinical trials in a reliable registry can provide the transparency of the study. Although the registration of clinical trials has increased remarkably, the integrity of the data is not always satisfactory. In this study, we analyzed public clinical trial databases updated by the Ministry of Food and Drug Safety (MFDS) and Clinical Research Information Service (CRIS) registry to provide an overview of the trends of clinical trials approved between 2017 and 2019 in Korea. Information on clinical trials approved between January 1, 2017 and December 31, 2019 was collected from two databases. Trial information was categorized and summarized by study phase, therapeutic area, and location of the participating centers. A total of 655 to 715 clinical trials were newly approved annually by MFDS during the period from 2017 to 2019. Phase 1 clinical trials accounted for the largest proportion (31.0%), followed by phase 3 (29.5%), investigator-initiated trials (24.1%), phase 2 (14.6%), and phase 4 (0.5%). The number of clinical trials classified as an Antineoplastic and immunomodulating agent was the greatest (40.1%) regardless of the study phase. The similar result was obtained from CRIS registry where therapeutic area Neoplasms (15.9%) accounted for the largest number. The number of clinical trials performed in Seoul and Gyeonggi-do was approximately 70% of the total trials. In conclusion, our study provided a comprehensive overview of clinical trials in Korea from 2017 to 2019. The discrepancy between clinical trial registries could be resolved by introducing standardized database and guidelines.

Information Transparency in Drug Development: Evidence from Mandatory Disclosure of Clinical Trials

Using the Food and Drug Administration Amendments Act of 2007 (FDAAA) that requires drug developers to disclose detailed clinical study results publicly, we examine the effect of information disclosure on drug development. We find significantly more suspensions of new drug projects after the FDAAA with a causal interpretation based on difference-in-differences analyses. Further evidence supports peer learning as a mechanism for the increased suspensions after the FDAAA. We also analyze social welfare implications of enhanced information disclosure; while the FDAAA helps improve drug quality, it leads to more suspensions of potential new drugs that could have reduced mortality and morbidity.

Commitments by the biopharmaceutical industry to clinical trial transparency: the evolving environment

Clinical trial sponsors have ethical obligations to register protocols, report study results and comply with applicable legal requirements. To evaluate public commitments to trial disclosure and rates of disclosure by...

Statistical guidance for responsible data sharing: an overview.

Since at least 2004 there has been a focus on data sharing and clinical trial disclosure with the requirements for protocols to be registered in clinicaltrials.gov and for subsequent manuscripts of the study results to be accepted for publication by major journals [1]. However, sponsors of clinical trials have for many years been widely criticised for not adhering to these requirements and failing to disclose clinical trials in a timely fashion (e.g., www.alltrials.net].

The evolution in registration of clinical trials: a chronicle of the historical calls and current initiatives promoting transparency.

Quality of care is strongly influenced by evidence-based medicine, a large part of which is based on results obtained from clinical trials. If trials are conducted in secret, patient safety is at risk. Several mandates-legal, editorial, financial, and ethical-have tried to influence the disclosure of clinical trials, first by encouraging registration in publicly accessible registers and, second, by calling for the publication of results. Not all these initiatives have reached high rates of compliance, but the succession of national and international events over a few years gave an important boost to information disclosure. This article provides a chronicle of the succession of the events, from the historical calls to the recent EMA policy and WHO statement, and public consultations requested by the NIH, and the HHS, which will inevitably change the international panorama. The path of these new policies is moving towards more supervised clinical research. Individual scientific institutions can also contribute, at the local level, to such an ethical endeavor as is improving research transparency, by disclosing information on the trials coordinated by their own researchers. The way is long and complex, but, if everyone contributes there could be a prompt, worldwide diffusion of the findings of clinical trials, and therefore a more possible evidenced-based medicine.

WHO calls for full disclosure of clinical trials

Online commenters support a push by the World Health Organization to publish results from human medical studies.

Clinical trial transparency: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved recently in Europe

Background:Previous studies have raised concerns around the transparency and disclosure rates of clinical trial results on clinical trial registries and in the scientific literature. The objective of this study was to assess the timely disclosure in the public domain of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) over a recent 3 year period.Methods:The study surveyed various publicly available information sources for both clinical trial registration and disclosure of results (including clinical trial registries, the International Federation of Pharmaceutical Manufacturers and Associations [IFPMA] Clinical Trials Portal, EMA European Public Assessment Reports and PubMed), searched from 27 December 2012 to 31 January 2013. The study covered all 53 new medicines (except vaccines and fixed-dose combinations) approved for marketing by 34 pharmaceutical companies by the EMA in 2009, 2010 and 2011. It included all completed company-sponsored clinical trials conducted in patients and recorded on a clinical trial registry and/or included in an EPAR.Outcome measure and results:The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 January 2013 (end of survey). Of the completed clinical trials associated with all 53 new medicines approved by the EMA between 2009 and 2011, 77% had results disclosed within 12 months. By 31 January 2013, this had increased to 89%. Rates of results disclosure within 12 months were 71%, 81% and 86% for new medicines approved in 2009, 2010 and 2011 respectively. Disclosure increased to 86%, 93% and 91% respectively by 31 January 2013. Although this was a purely quantitative study which did not aim to assess the content of disclosure against any specific requirements, limitations relating to a number of difficulties in finding all relevant data from multiple sources in the public domain were captured.Conclusions:Results of over three-quarters of all company-sponsored clinical trials related to new medicines recently approved by the EMA were disclosed within a year of completion or regulatory approval, and almost 90% were disclosed by 31 January 2013, suggesting transparency is now better than has sometimes been reported previously.

Clinical trial disclosure toolkit released by ABPI

Clinical trial disclosure toolkit released by ABPI

Prospective registration and results disclosure of clinical trials in the Americas: a roadmap toward transparency.

The objective of this article is to propose a roadmap toward transparency of clinical trials in the Americas by their prospective registration and results disclosure. This will broaden access to more complete and accurate data and facilitate evidence-informed decision-making and participation in research. Consequently, it should have a positive impact on people's health and should promote trust in health research. Existing initiatives were identified, registration of trials was analyzed following the World Health Organization (WHO) standards on trial registration, and a roadmap is proposed to address the gaps in advancing transparency. The analysis shows that, in spite of numerous regional and country initiatives, clinical trials taking place in nonEnglish-speaking parts of the Americas are underregistered. A roadmap is proposed to enhance research governance and good research practice by improving the transparency of clinical trials. The proposed roadmap includes strategies for implementing WHO international standards for trial registration, for developing international standards of public disclosure of trial results, and for a potential role of the Pan American Health Organization.

Clinical Trial Disclosure: Global Overview and Implications of New Laws and Guidelines

Clinical trial disclosure has received much international attention. The US Congress has enacted the Food and Drug Administration Amendments Act of 2007 (FDAAA), also known as Public Law 110-85. Section 801 of FDAAA requires public registration of new or ongoing clinical trials and disclosure of results for completed clinical trials on the public database ClinicalTrials.gov. FDAAA has provisions for proof of compliance and authorizes penalties for noncompliance; several phases will be implemented over 3 years and completed by 2010. In the European Union (EU), the European Parliament enacted the Clinical Trials Directive (Directive 2001/20/EC of April 4, 2001), which governs public access to information on clinical trials in the European Community. Article 11 of the Clinical Trials Directive, enforced by the European Medicines Agency (EMEA), deals with the exchange of information among the EU member states. In some cases, it also deals with the countries of the European Economic Area. The directive is accompanied by two regulations; one refers to clinical trials in general, and the other applies specifically to trials in the pediatric population. These regulations describe how some of the protocol and results information in the EudraCT database at EMEA will be automatically released to the public through the EudraPharm database. The public release is planned for 2010 and 2011. Requirements for clinical trials disclosure have also been established at the national level in several countries. A summary is presented here of the key global requirements for public disclosure of clinical trial information on drugs, biologics, and medical devices, with a brief overview on the position of various stakeholders involved in this important and evolving topic.

The Emergence and Growth of Clinical Trial Information Transparency

Clinical trial disclosure initiatives have slowly emerged in response to stakeholder and public response to questions of safety and efficacy of drugs and perceived secrecy by the pharmaceutical industry. Originally, clinical trial disclosure and transparency activities focused upon therapeutic compounds of interest to seriously ill patients who hoped that by participating in clinical trials, they might contribute to the development of effective drug treatments for their disease and to the common good. Over the years, additional stakeholders have entered the discussion, causing an expansion in the transparency requirements, from meeting patients' and their physicians' needs for information to meeting researcher, insurer, and legislator needs. This article provides a brief look at the history of the clinical trial disclosure initiative as it has evolved worldwide.

Operational Issues in Clinical Trial Disclosure of Global Trials

In hospitals and clinics around the world, ordinary people place their health and their very lives in the hands of researchers who test new experimental drugs for safety and effectiveness. The public and legislators worldwide have expressed increasing interest in understanding how clinical trials are conducted and the results of those trials. The list of stakeholders has grown substantially in recent years to include medical and scientific academia, government agencies, regulatory authorities, and advocacy groups. Quite logically, stakeholders’ interests have shifted slightly from the registration of clinical trial protocol information to the posting of clinical trial results upon trial completion. Protocol registration and results reporting requirements are staggering, diverse, and complex. This article provides a look at industry experience with the operational challenges of clinical trial registries and results databases that the pharmaceutical, medical device, and biotechnology industry, and academia face when providing clinical trial information.

Clinical Trial Registries: An Industry Perspective

In recent years an explosion has occurred in the disclosure of clinical trial information through clinical trial registries, partly driven by legislative demands and the requirement by a group of pharmaceutical journals for increased transparency. As a consequence, a large amount of information is now available to the general public and health care providers. In complying with the disclosure requirements, different pharmaceutical companies have chosen different approaches in providing clinical trial information. We conducted a survey among a sample of pharmaceutical companies of varying size to determine their views on the current situation, the challenges they face, and the future of the clinical trial disclosure initiative. Key learnings were that, in their view, transparency has improved substantially, but more so for the scientific community than for the patient. Patient awareness is thought to be relatively low. The increasing demands of legislation cause challenges for companies both in interpretation and in resource requirements, and it was thought this may cause the industry and the whole initiative to lose sight of the original aim, which was to improve transparency for the general public and the patient. Particular challenges mentioned include the new requirements for clinical trial data disclosure and the provision of lay summaries, the proliferation of registries with the associated potential confusion for patients, and the increasing complexity of legislation. Overall, survey respondents concluded that while much has been achieved, more remains to be done, and that patient needs should take priority.

Law Ensures Public Access to Clinical Trial Disclosures

Law Ensures Public Access to Clinical Trial Disclosures

WHO Announces Standards for Clinical Trial Disclosure

WHO Announces Standards for Clinical Trial Disclosure

Full clinical trial disclosure needed: expert

Legislation is required to force pharmaceutical companies to disclose clinical trial information to Canadians, says Dr. Andreas Laupacis of the Canadian Expert Drug Advisory Committee (CEDAC). Laupacis, who emphasized that he was speaking as an individual, told attendees at a recent Centre for

House subcommittee holds hearing on clinical trial disclosure

House subcommittee holds hearing on clinical trial disclosure

Comment from the editors

Comment from the editors