Imperatives to Share Trial Results with Volunteers

Henri-Frederic Ariel, a 19th Century philosopher once said: "The greatest need of all human beings is to be appreciated. And the highest form of appreciation is through one's acts and deeds." All clinical research professionals would agree with his statement but sadly, that agreement is not necessarily translating into practice.

Kenneth A. Getz

Nowhere is this more apparent than in the communication of clinical trial results to the individuals who volunteer to participate in government- and industry-funded clinical trials. Clinical research volunteers want to know that their participation matters and that it is appreciated. This is clearly not the message that they are receiving: whereas 97% of study volunteers in 2011 expressed interest in obtaining the results of clinical trials in which they participated, a similarly high percentage (91%) never actually did. And of the 9% who learned of their clinical trial results, according to the non-profit Center for Information and Study on Clinical Research participation (CISCRP), one-third of them stumbled upon the findings published years later in a major national newspaper.

Poor quality and low compliance

Many research professionals are quick to point out that access to Phase II-IV clinical trial results is mandated and now publicly available on the National Library of Medicine's (NLM) clinicaltrials.gov website. However, recent papers published in the New England Journal of Medicine and in Health Affairs suggest otherwise. Although clinicaltrials.gov is easily reached online, it is rife with missing and incomplete information, data inconsistencies, and areas of poor data quality.

Research sponsors appear to be shirking their obligation. The Food and Drug Administration Amendments Act (FDAAA) of 2007, Section 801, mandates the submission of summary clinical trial results data for Phase IIb–IV studies whether the results are conclusive, inconclusive, published or not. The mandate stipulates that failure to comply may result in a substantial civil penalty of up to $10,000 per day or the withholding of NIH grant funding if noncompliance remains uncorrected 30 days after the violation has been cited. Research sponsors are permitted to delay reporting results for up to three years for clinical trials conducted before drugs are initially approved and for studies of unapproved new clinical indications for those drugs already approved.

The Declaration of Helsinki (2008; Guideline 33) similarly obligates sponsors and research professionals to provide clinical trial results to study volunteers. At this time, however, the European Medicines Agency does not yet make summary results information publicly available for clinical trials of approved and unapproved drugs conducted in the European Union.

In a March 2011 New England Journal of Medicine article, research professionals at the NLM and the Duke Translational Medicine Institute at Duke University note the challenges of maintaining data quality under the limitations of self-reporting. In their review of data in the registry, the authors note missing and invalid data as well as data that is difficult—if not impossible—to verify (e.g., invalid or implausible data elements; vague and meaningless data entries; inconsistent data; and unclear trial designs and objectives).

In a Health Affairs December 2011 article, Michael Law and colleagues present very disturbing findings suggesting that sponsors are largely paying lip service to mandatory clinical trial results disclosure. Law found that of the 4,455 completed trials registered between September 1999 and May 2010, less than one in 10 (only 7.6%) sponsors eventually reported their results on clinicaltrials.gov. Not only is reporting compliance extremely low, but also—and even more troubling—government agencies are nearly four times less likely to report results than are industry sponsors (see figure). Some sponsors may have received an exemption to delay listing their results—a condition that is not made publicly available. As such, the very low level of compliance may be somewhat higher.

Low Levels of Compliance Reporting Trial Results

Law and colleagues also note that the majority of government and industry sponsors are not reporting results within the one-year mandated timeframe.

Not for patients and the public

For research sponsors, the penalties for noncompliance and incomplete reporting are not enough of an incentive if they are not enforced. Perhaps more importantly, it is increasingly evident that http://clincialtrials.gov is not the ideal mechanism to disclose trial results to its intended audience—patients and the public. The majority find locating their specific trial extremely difficult. Even if they are able to conduct a successful search, the public and study volunteers find that trial results on the NLM registry are highly technical and difficult to understand and interpret.

Since its inception, researchers, policymakers and life sciences analysts are the parties primarily accessing trial results on http://clinicaltrials.gov. The NLM, in its recent New England Journal of Medicine article, acknowledges that research professionals are its primary audience. The authors add that although the registry is designed to benefit the general public by creating greater transparency and access to clinical trial results, "different parts of the database are likely to be of more or less direct use" to this audience. The NLM explains that it expects the utility of the http://clinicaltrials.gov registry to increase over time as more results are posted.

An imperative and an opportunity

Failure to responsibly and responsively disclose clinical trial results is a public relations crisis waiting to happen. The already tenuous relationship and eroded trust between the clinical research enterprise and the public cannot endure another indictment that sponsors are not accountable and are failing to disclose, or worse concealing, important safety information from the public and patients. Clinical trial volunteers deserve a full commitment and best effort to communicate trial results. Even more, volunteers shouldn't have to initiate and conduct a search for their trial results; but rather volunteers should receive them in a timely manner and in a form that is easy to understand. This is the ultimate act of appreciation that the clinical research enterprise can show those who have given their participation so that professionals can perform their work and public health can advance.

The perceived risk of divulging trial results is far less than the risk of failing to do so. It is the right thing to do—whether it is mandated or not. Failure to communicate trial results is also a profoundly missed opportunity for the research community to rebuild public trust, and establish and nurture relationships with study volunteers.

CISCRP notes that an overwhelming majority of investigative sites (98%) also want to provide trial results to their study volunteers. Site personnel feel that it is not only their moral obligation to do so, but also an essential way to strengthen the relationship with their study volunteers and an opportunity to maintain contact with patients who have completed participation. Site personnel feel that their patient relationships are compromised when they are unable to provide results and they too feel valued as partners when research sponsors share trial results with them. For all of these reasons, there is a strong business imperative for research sponsors to proactively and routinely communicate trial results.

Since 2010, CISCRP has been working with select research sponsors to address this critical need to make the communication of clinical trial results to study volunteers a priority and a standard practice. CISCRP piloted a program with Pfizer in 2010 and demonstrated the feasibility and impact of developing, producing, and providing results summaries to study volunteers via investigative site personnel. The program has been reviewed by regulatory agencies and ethical review committees and it utilizes a unique lay-specialty editorial board. Results of the pilot are described in an Applied Clinical Trials October 2010 article and the results of a much larger beta test will soon be published in a major peer-reviewed journal.

At this time, 13 pharmaceutical and biotechnology companies are supporting the initiative but many more sponsors are needed to adopt this program and move the clinical research enterprise from taking a reactive and proscriptive approach to listing clinical trial results on the NLM website to proactively demonstrating deep appreciation to all of its study volunteers.

In 2012, it is unconscionable and inexcusable that research sponsors are not routinely communicating trial results to their study volunteers. We owe it to the millions of people who give the gift of their participation every year but still never learn that their participation made a difference.

Kenneth A. Getz MBA, is a Senior Research Fellow at the Tufts CSDD and Chairman of CISCRP, both in Boston, MA, e-mail: kenneth.getz@tufts.edu