About a month ago, we published a post examining the friction, in clinical trials, between the demand for transparency and the protection of confidentiality. Regulators recently published guidelines for reporting the results of European clinical trials; in the U.S., there have been calls for improved compliance with reporting requirements1. This is a discussion that often focuses on the back end of the clinical trial process: the degree to which reporting trial results is beneficial to medical science, and the degree to which it compromises patient privacy and commercial advantage.
But transparency also comes into play as early as the moment when trials are, or aren’t, registered on ClinicalTrials.gov, a public database allowing anyone with an internet connection to access information about active or completed trials. There are currently 212,596 trials listed on ClinicalTrials.gov, of which 32,035 are Phase I trials2. While this seems to be a sizeable portion of the total, it does not necessarily represent all Phase I trials currently in progress: of all controlled investigational trials of drugs, biological products, or devices subject to FDA regulation, Phase I trials are the only ones that are not required to register on the database3.
ClinicalTrials.gov didn’t make this rule; it was the U.S. Congress that decided to exempt Phase I trials from the registration requirement. And in some circles, the move was not exactly popular: numerous organizations, included the World Health Organization, the Society for Clinical Trials, and more, have advocated for more ubiquitous registration of all trials, including Phase I. ClinicalTrials.gov itself, in the interest of being as comprehensive as possible in its documentaion, encourages trials of all phases to register even if they are not required to do so. They believe that registration can benefit anyone, from the public to the research community, with an interest in clinical research. This could mean laypeople with an academic interest, or professionals looking to perform systematic reviews or analyze methods and findings in order to enhance future studies.
Reasons to Register
Registering a Phase I trial on ClinicalTrials.gov is not only beneficial for informational purposes; it could have practical applications for the research industry as well. Later stage trials depend on the dosage levels and adverse event data gathered during Phase I, giving Phase I a fundamental importance that necessitates that patients, both actual and potential, are comfortably informed and enticed to participate. Indeed, patient engagement is increasingly seen as a high priority in clinical research. The method of engagement currently in vogue appears to be through recent technology such as mobile apps4, but registering a trial on the database would create an openness that could bolster these efforts. In addition, a lack of awareness of clinical trial processes, and even of the existence of clinical trials, is one of the leading causes of recruitment challenges. Declining to register a trial is counter-productive to maintaining the visibility that these concerns make necessary.
So why might a sponsor resist this encouragement to register? As mentioned in the post last month, the motivation could be proprietary: sponsors may not wish to publish their study design, drug name, or other details in a database that their competition could access. And from a reputational standpoint, perhaps some sponsors see publishing a record of a clinical trial as a recipe for undesirable public relations if that trial is terminated or suspended before moving on from Phase I. Whatever the reservations may be, ClinicalTrials.gov hopes to counter them by making registration easy and unbureaucratic: trials are free to register, and can be registered either before or after patient enrollment has begun5.
Of course, voluntary Phase I registration is not uncommon; as discussed above, thousands of them are registered as of this writing. Representatives at ClinicalTrials.gov would likely praise the sponsors of these trials for understanding the value, both to their colleagues in the research community and to the public, of creating transparency about their work.
1 WHO calls for increased transparency in medical research; World Health Organization; 14 April 2015
3 FDAAA 801 Requirements; ClinicalTrials.gov; November 2015
4 Head, Curtis; The Patient Experience in Tomorrow’s Clinical Trials; PRC Clinical; 2 November 2015
5 Frequently Asked Questions; ClinicalTrials.gov; February 2015