Fixing Broken Trials: Wasted Research and Failure to Report

Fixing Broken Trials Wasted Research and Failure to Report

On September 7, The Conversation, which is a respected “network of not-for-profit media outlets that publish news stories written by academics and researchers,” published, “Medical research is broken: here’s how we can fix it.” Noting that about $200 billion is spent on global health research, they also report that, “millions of people volunteer their time to be participants in health studies.” Despite these facts, the piece argues that, “about 85% of all research is simply wasted.” First, 50% of trials are never published; especially those that are inconclusive or negative, so-called “null results.” Hence a study that finds a drug effective is “much more likely” to be published than those that find no evidence of said drug working. Of published studies, many are poorly designed. Taken together, all these facts mean that, “precious resources can be wasted on treatments that don’t work, or may even harm patients.”

“Colossal Waste of Research”

Also, a lot of published studies do not fully or accurately report on how “the study was conducted and what was found.” This can lead to questionable practices like selectively publishing results and failing to report financial and/or political conflicts of interest. And doctors and patients can’t fully understand the evidence available with these transparency issues. For decades, these problems have been talked about in the medical profession, “but this is a scandal that appears to be barely known by the wider public.” This, “colossal waste of research is avoidable.” Meta-research, or research studying research, offers some tools to understand how to solve the problems under discussion. In spite of this, there are now COVID-19 trials, “that are badly designed and lack transparency.” Today, the question is not “what?” the answers are but instead “why?” we’re not using them. 

Three-Steps to Better Research Transparency and Reporting  

To deal with these concerns, an international collection of doctors, patients, and researchers has  created a Declaration to Improve Biomedical and Health Research. It has three steps that are immediately available to improve research:

“1) All research that is funded by the public or a charity should be catalogued and stored in a central website open to everyone. This should include detailed study documents, such as protocols and a summary of the results. Cataloguing all research would help increase the number of studies with negative results being read and would be a huge first step to reducing research waste.

2) Mandatory publication of all authors’ interest. Examples include any financial or political interests that may bias the study’s results. There have already been documented cases of funders influencing the findings of studies, which has already led to patients being irreversibly harmed. In several countries, so-called “sunshine acts” require doctors to disclose financial interests. But this has not yet been made mandatory in all countries.

  3) Registered reports is a publication format where authors submit their study protocol to a journal for review before recruiting any patients. That way, reviewers can give feedback on the study design before it starts, rather than the current process of reviewing after it is complete and too late to change. A bonus of registered reports is that they’ve also been found to increase the number of studies with negative results being published. This is a promising solution currently in use by over 250 journals, but it’s a format that can be used by all journals.”

Sponsors Flouting 2017 Final FDA Guidelines?

Back on January 17, Reuters Health took a look at how US law on clinical trials is at times ignored, with results going unreported. Less than half of trial sponsors reported results to the US government registry in the year after trial completion as required by law, “flouting US law and risking fines.” Based on a study in The Lancet, it is noted that despite clear past lapses in reporting negative trials results, “many sponsors are still not reporting their findings, potentially keeping patients and doctors in the dark about benefits and side effects of treatments.” Study leader Dr. Ben Goldacre of Oxford said, “Doctors and patients cannot make informed choices about which treatments work best when the results of clinical trials are withheld.”  

The study aimed to see if sponsors were in fact complying with 2007’s U.S. Food and Drug Administration Amendments Act in light of final guidance that was completed in 2017. Under the law, US trial sponsors are to report data within a year of a study’s completion, and they are to be fined $10,000 per day. Goldacre and his team looked at 4,209 trials registered at ClinicalTrials.gov that were due to report results from March 2018 to September 2019. The finding? Only 41 percent of results were “reported promptly” and one out of three trials, “remain unreported.” The proportion of trials meeting the deadlines has not changed since July 2018, and “progress has stalled.” Goldacre opined, “We’ve known about this problem for at least three decades. It took us 25 years to get to the point of passing the law in 2007. It took another 10 years to have the final rule implemented. After all of that time, we now see that law is being very, very widely ignored.” 

Of sponsors with data expected, Novartis, Gilead, GlaxoSmithKline, Pfizer, and Roche, “had reported at least some data on all of them.” On the other hand, University of Texas’ MD Anderson Cancer Center had published data, “on only 71 out of 85 trials.” The National Cancer Institute submitted data for only 65 of 79 trials.  Meantime, “Goldacre said his paper is the first to fully assess compliance with the law since final rules were clarified in 2017 and offers a ‘deep analysis’ of all the data, factors associated with poor compliance and reporting trends over time.” He also notes that FDA’s lack of enforcement, “may be contributing to the problem.”