A question of transparency with clinical trials

 

Why this matters, the TrialsTracker creators say, is that “Clinical trials are the best way we have of testing whether a medicine is safe and effective. They can involve thousands of people, patients and healthy volunteers, and take years to complete. But trials with negative results are twice as likely to remain unreported as those with positive results. This means that patients and doctors don't have the full information about the benefits and risks of treatments. We believe all clinical trials, past and present, should be reported in full.”

 

On the positive side, several trial sponsors do show transparency in their clinical trials results. Shire, for example, has had 96 eligible trials finish up during the surveyed period, and published results for all of them. Some of the others with a high level of transparency include Colgate Palmolive (only 3.1% of their eligible trial results missing), Bristol-Myers Squibb (4.3 percent), Ely Lilly and Co. (5.1 percent), Johnson & Johnson Pharmaceutical Research and Development LLC (5.2 percent), Allergan (5.4 percent), Genentech (5.7 percent), AbbVie (7 percent) and Janssen Research and Development LLC (8.6 percent), and a few others with less than 10 percent of study results left unpublished.

 

On the other end of the spectrum, Ranbaxy Laboratories Ltd. has not published results for any of the 35 trials it completed between 2006 and 2014 and several others have similarly dismal figures in the 80 percent to 90 percent range, including a couple relatively big names like City of Hope Medical Center and the National Institute on Drug Abuse.

 

And at this point in this article, as Chief Editor of DDNews, I’m going to admit that things will delve a bit into the realm of critical conjecture and even some editorializing, given the way that the results are presented.

 

Going to TrialsTracker, the default sorting of the trial sponsor “rankings” (and you can sort by a variety of means yourself) puts several big names as “bad players” in the top five, among them Sanofi, Novaris Pharmaceuticals, the National Cancer Institute, GlaxoSmithKline and the Mayo Clinic.

 

Some media stories about the TrialsTracker findings, both media outlets inside and outside the pharma/biotech industry, have therefore singled out Sanofi and Novartis as the two worst offenders in terms of lack of clinical trial transparency, based on the sheer number of trials that are missing results, with Sanofi missing results for 285 of 435 eligible trials in the 2006-2014 period and Novartis missing 201 of 534.

 

On a percentage basis, though, that puts Sanofi at 65.5 percent missing and Novartis at 37.6 percent, which may or may not make them the “worst” depending on whether one finds the sheer numbers of the percent of the total the more meaningful figure.

 

In talking about their methodology the TrialsTracker creators admit there are limitations, noting, “We include all interventional trials completed between Jan 2006 and two years ago, except for Phase 0/1 trials and those that have made a formal request to delay results. Next, we look for summary results on ClinicalTrials.gov, or linked results on PubMed. Our table includes only sponsors with more than 30 trials ... We understand this method isn't perfect. However, we feel that researchers have a clear obligation to ensure that their results are published, and discoverable.”

 

While it likely would not significantly change the overall numbers and rankings, the lack of reporting on companies’ performance in reporting on trials completed in 2015 and 2016 (TrialsTracker results were current as of October 2016) does potentially skew matters, as it would be hard to know if in more recent years with more recent trials that corporate, academic and other sponsors might be improving their transparency.

 

And, as Novartis noted in a statement to FierceBiotech when the website wrote about TrialsTracker in recent days, “We are aware of the TrialsTracker initiative and are reviewing against our own records. Initial analysis suggests the data presented is misleading as it focuses on PubMed and clinicaltrials.gov records, but doesn’t include other publication outlets including our own clinical trials results website www.novartisclinicaltrials.com.” For the rest of Novartis’ statement, you can read the FierceBiotech story “Sanofi, Novartis, NCI, Ranbaxy top missing data list as Shire most transparent.”

 

Now, there are certainly reasons for concern looking at what TrialsTracker has uncovered. One would be that GlaxoSmithKline, for example, has failed to report on 22.6 percent of its trials completed between 2006 and 2014, and yet a few years back it signed up to the United Kingdom-based AllTrials clinical trial transparency register, pledging to release all data from its trials.

 

And the fact is that publishing all trials results, even the unfavorable ones, is helpful to future research and to future trials. Pharma and biotech companies and other trials sponsors often complain about the cost of trials and sometimes difficulty getting participants, and the idea that so much work would go into the effort and no one would see the results runs counter to trying to encourage people to engage in and trust the system.

 

As Síle Lane, director of campaigns at Sense about Science, which runs the AllTrials campaign, has said, “We should all be outraged that in the last 10 years 8.7 million patients have taken part in trials that haven’t published results. These people volunteered for a clinical trial trusting that whatever was found out in the trial would be shared with doctors and researchers and used to make life better for patients like them. When results from trials are never shared and never used, that’s an enormous betrayal of their trust.

 

“I hope this new tracker will focus trial sponsors’ minds on the information they haven’t shared. The situation is urgent. When researchers retire, when computers break, when notebooks get lost we lose more knowledge about our medicines. Every day that passes means more information is lost forever. Trial funders need to ensure that missing results are shared, now, before it’s too late.”

 

And then Dr. Ben Goldacre, one of the founders of the AllTrials campaign for clinical trial transparency and one of the academics behind the TrialsTracker: “Everyone has been talking about this problem for far too long. We hope that increasing accountability will help to drive change forward. The TrialsTracker helps to identify the individual universities and companies with the most overdue trials. If any institution is concerned that it is doing badly in our league tables, then there is one simple thing they can do: publish their trial results, using their trial registry number, so that this information can be accessed and read by doctors, researchers, and patients.”

 

Finally, April Clyburne Sherin, AllTrials U.S. manager with Sense about Science USA: “TrialsTracker is a tool that helps align the values of responsible research groups with their actions. It empowers them to assess gaps in discoverability and take the concrete steps required for transparency; this will ultimately improve the reporting quality and impact of their research.”

 

Whether or not the methodology of TrialsTracker is fair enough and whether or not trial sponsors are possibly making their data available enough or publishing it where it can be easily found are among the questions worth asking moving forward.

 

The truth is that with companies in particular, in search of investors or in need of satisfying shareholders, there is pressure not to release “bad news.” But at the same time, without more complete data, how are future researchers to advance without re-making the mistakes of others, how are regulators and ethics committees to have the full picture they need and how are patients and physicians to accurately make informed decisions on benefits and risks of therapeutics—approved or experimental?