A call for action for summary clinical reports

Richeek Pradhan is a Ph.D. candidate in Pharmacoepidemiology at McGill University.

If you want to find out what Lady Gaga’s met gala costume looked like, or where Queen Elizabeth dined last night, you Google. In a world that spins out terabytes of data every day, awareness of the minutest triviality is the norm. It is intriguing, thus, when data regarding some of the most important aspects of our lives remains hidden from public access.

Clinical research with human participants, traditionally, has been one such domain where transparency regarding conduct and results of the research has been far from ideal, particularly if the studies yield negative or unfavorable results. In the last few decades, however, major scandals involving the pharmaceutical industry and countless petitions from various stakeholders have triggered formulation of novel mechanisms to convert sharing results by the investigator from a matter of prerogative to a matter of responsibility. To enhance transparency, registration of trial protocols in clinical trial registries has been made mandatory, and sharing of summary results in those registries encouraged, over and above the usual way of publishing results in journal articles. In fact, the need to make research results available to public is enshrined in the Declaration of Helsinki,  the World Medical Association’s guidelines for research with human participants.

The benefit of reporting results in trial registries can be best appreciated when we think how evidence informing medical practice guidelines is generated. The usual procedure is to look at systematic reviews that have compiled all available evidence, stacking both positive and negative results together, to arrive at a conclusion. The problem is that journals tend to publish only positive, newsworthy studies (aka publication bias). Thus, the stacked evidence becomes inaccurately skewed. Reporting summary results irrespective of outcome in trial registries makes them de facto archives of all conducted studies. Indeed, the use of trial registries in systematic reviews is associated with low publication bias, and thus a resource ensuring better evidence generation for guidelines. There are several other advantages: not having barriers of journal page count means that registries contain a wider range of data, the registries are open access and thus accessible to the general public/researcher who is unlikely to pay journal subscription fees, and there are automatic data extraction tools to download such data in format amenable to statistical methods needed to conduct systematic reviews.

Other novel pathways of data sharing exist, but on their own may be insufficient to surpass all the benefits afforded by reporting results in registries. For example, in a recent move to increase transparency, Health Canada has started publishing results of studies used to seek regulatory marketing approval for drugs, biologics, and medical devices, irrespective of whether the approval was granted or denied. This, however, only partially addresses the issue of data obfuscation in clinical trials because of several reasons. First, the rule currently deals with only studies that are presented to Health Canada for marketing approval of new drugs/devices, thus covering only a fraction of all clinical studies conducted (e.g., older drugs/devices, non-pharmacological/device related studies). Second, since the sponsors put forward these studies to seek regulatory approval, more often than not, they will only have favorable results. Finally, unlike registries, this mechanism of publishing results does not track changes between planned and post-hoc analyses conducted in the study, such changes often implemented to fish for results that suit the researchers. Registering study protocols in clinical trial registries and reporting of summary results in these registers form an essential way of data-sharing that should not be done away with because of Health Canada’s sharing of trial results.

So how do Canadian universities fare in result reporting in registries? Health Canada does not have it’s own clinical trial registry, but it encourages registration of trials in ClinicalTrials.gov, the trial registry for the US Food and Drug Administration. Furthermore, public reporting of results is mandatory according to the Tri Council Policy Statement, the ethical standards for federally funded research. Despite this, the major Canadian research universities have poor rates of reporting trial result in registries like ClinicalTrials.gov. For trials completed before December 2017, percentage of interventional studies without summary results reported in ClinicalTrials.gov are 94% where University of Toronto was the lead sponsor, 96% for University of British Columbia, 92% for McMaster University, 91% for McGill, and 92% for University of Ottawa.

Reporting of results in registries, while not trivial, does not require expenditure of either money or manpower in excess of what is already required to run a trial. Why then is the result-reporting rate of Canadian universities so low? The fact that pharmaceutical companies outperform academic investigators in result reporting ]indicates the reason perhaps is not concerns regarding intellectual property. At the moment, the lack of awareness of the result reporting requirements and ignorance regarding the benefits of such reporting seem to be important contributory factors. However, recent example from the UK, where the result-reporting rates in all major universities have gone up to 90% or more in just the last few months, shows that change is possible, and need not be particularly time taking. Raising awareness among researchers, persistent activism, mandates from the funding agencies and pressure from the government have worked together to engender change, and in doing so provided a model that can be followed elsewhere.

Canadian physicians and researchers too have an important role in improving the trial reporting rates of their universities.  After all, they are major stakeholders in the enterprise of evidence synthesis and formulations of clinical practice guidelines. If the guidelines that are inaccurate, their patients will suffer. It is therefore critical that physicians and researchers themselves report their study results in registries, and spread awareness about doing so among their colleagues. Demands must also be made to the funding agencies like the Canadian Institutes for Health Research to ensure that researchers meeting summary result reporting expectations. Together, it can be ensured that research conducted in Canadian universities is transparent, and its results are accessible to all.

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