Parkinson Pipeline Project-treatment development database, research, FDA drug approval, PD clinical trials and sponsors, patient involvement

Better Reporting of Clinical Trial Results

What is being done to improve the clinical trial reporting process?

Mandatory trial registration

Trial registration benefits everyone involved by:

“Making it easier for patients to locate trials for which they might be eligible and through which they might access new therapies.
Making it more difficult to suppress knowledge of investigations being done, and hence helping to counteract the distorted efficacy and safety profiles that arise from the selective publication of trial results.
Helping in the assessment of existing completed trials. Peer reviewers, editors, commentators and individual physicians and patients are able not only to examine published work in a particular field but can also see what is coming down the trial pipeline… and might be advised to wait for its results before using the new drug.” ⁽¹⁶⁾
“The success of the health research enterprise depends on transparency in research and knowledge sharing. Only by registering trials prospectively can we be sure that all trials that are undertaken are also reported.” ⁽⁵⁾
With this in mind, the International Committee of Medical Journal Editors (ICMJE) implemented a policy requiring registration of clinical trials as a prerequisite for consideration of publication of the results. This prompted “large increases in the number of trial registrations recorded (at ClinicalTrials.gov) between May and October 2005,” and more complete database entries, though “there still is room for substantial improvement.” Trial Registration at ClinicalTrials.gov between May and October 2005

Full disclosure of required information

Researchers from the National Institutes of Health found that many of the registered trials fail to give critical information, such as the name of the drug being studied and what the trial is trying to determine. “The editor of the New England Journal of Medicine (NEJM) called on doctors to boycott clinical trials sponsored by pharmaceutical companies that do not fully live up to the spirit of legal requirements to register such research efforts.” ⁽¹⁴⁾

“It is unacceptable for a trial sponsor not to register its trial in a complete, meaningful and timely fashion,” said Dr. Jeffrey Drazen, editor of the NEJM. “We call for all clinical investigators and patients to participate only in fully registered trials. If a company realizes that secrecy and failure to register mean that it cannot meet its recruitment goals, it will quickly recognize that the consequence of that secrecy is commercial failure, not competitive success."⁽¹⁴⁾

"We demand complete compliance, because trial registration makes moral sense," Drazen said. "When patients put themselves at risk to participate in clinical trials, they do so with the tacit understanding that their risk is part of the public record, not merely the secret record of the sponsor."⁽¹⁴⁾

“Registration of trials should improve the completeness, reliability, and quality of the interpretation of clinical research.”⁽¹⁵⁾

Standards for reporting

High profile cases recently in the news have made the public skeptical about clinical trial results reported by sponsors in the drug, biologicals, or medical device industries, especially when the data “have not been subjected to external, independent peer review…and is not integrated with other data or indexed.⁽⁵⁾ Because academic researchers and their institutions often play a prominent role in such trials, these concerns challenge their integrity as well.⁽⁴⁾ “To strengthen the role of U.S. medical schools and teaching hospitals as trusted and reliable sources of research information, the Association of American Medical Colleges "(AAMC) announced new Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials.⁽⁴⁾ For a list of these “comprehensive guidelines that would direct the ethical and operational aspects of data access, analysis, and reporting of clinical research studies,”⁽⁴⁾ see AAMC Adopts New Principles for Reporting Results of Clinical Trials

“Researchers at academic medical centers should not be party to the release of misleading statements about trial results or to the suppression of outcomes unfavorable to a sponsor,” said (Association of American Medical Colleges) AAMC President Jordan J. Cohen, M.D. “Academic medical centers must honor the trust of the American public and scrupulously report their research results fully, credibly and accurately.”⁽⁴⁾

“It is essential that the goals, specifications, and endpoints of clinical trials be registered and made public,” according to a statement made by the Consumers Union. “It is a scandal that in some recent cases only portions of clinical trials that made a drug look good were made public, and portions that revealed danger and unacceptable risk — or lack of effectiveness — were hidden.”⁽¹⁰⁾

Hold public and patient interests above commercial interests

Many biopharmaceutical companies object to disclosing the current required level of trial data, saying it gives competitors too much information and jeopardizes their intellectual and commercial interests and rights. “Although protection of commercial interests is important, the social contract with trial participants must take precedence.”⁽⁵⁾

“The current situation, in which clinical trials involving human subjects are conducted behind the veil of ‘proprietary interest’ and are subjected to the scrutiny of scientific review only at the will of their commercial sponsors, is unacceptable on ethical and scientific grounds. There must be a better balance between ensuring the commercial viability of ‘R & D’ and serving the best interests of patients and the public. The public registration of clinical trials is one way to rebalance the scales.”⁽¹⁶⁾

The Ottawa Statement, endorsed throughout the international research community, “outlines fundamental principles for trial registration and how they can be operationalised.”⁽¹³⁾ Recognizing that “public availability of information about all trials is essential to ensuring ethical and scientific integrity in medical research,” the Statement calls for sponsors to “disclose the protocol details of all trials up front, disclose amendments along the way, and post the results at the end.”⁽¹³⁾ Clinical trial participants “assume potential risks in order to contribute to knowledge; investigators and sponsors are thus ethically bound to make information about the study protocol and results publicly accessible.”⁽¹³⁾ Not one drug company has endorsed this.⁽¹³⁾

The World Health Organization (WHO) has launched an International Clinical Trials Registry Platform (ICTRP) project, “setting international norms and standards for trial registration and reporting.” It outlines 20 characteristics of the trial that need to be registered, omitting many of the “crucial items” in the Ottawa Statement on principles for trial registration.⁽⁷⁾

Free, timely electronic access to trial protocols and research results

Trial registries give anyone, anywhere free electronic access to public repositories where information related to ongoing trials can be stored, searched, and accessed. In some cases, this includes the full text and data of published research.

The Public Library of Science (PLoS), “a non-profit organization of scientists and physicians committed to making scientific and medical literature a freely available public resource.”⁽⁶⁾ Its new “international, peer-reviewed open-access journal,” PloS Clinical Trials, will “publish the results of randomized clinical trials in humans from all medical and public health disciplines.”⁽⁶⁾ All published articles will be immediately and freely available online to read, download, redistribute, etc. PLoS Clinical Trials has no subscriptions or reprints to sell, making it beholden to no one.⁽⁵⁾ Each trial report will be accompanied by an editorial summary of its strengths and weaknesses, including what it adds to current scientific knowledge. Readers will have the opportunity to post comments.