“The only thing that has an impact is the kind of stuff you do,” the official told me, echoing a refrain was common among drug regulators in Europe only a few years ago. Yes, thousands of clinical trial results had never been made public. Yes, this was bad for science and bad for patients. No, there was nothing they could do about it.
We were just leaving a public event where I had been invited to speak based on my work with TranspariMED, a campaign group focused on improving clinical trial reporting. TranspariMED was pushing companies and institutions to follow the rules by publishing performance rankings, with some success. Many regulators quietly welcomed our efforts, but claimed that they themselves were powerless to act because European Union reporting guidelines were not legally binding.
A similar plea of regulatory helplessness is now being made in the United States. While the FDA does have legal powers to enforce a 2007 trial reporting law, it has so far argued that it does not have the resources to chase up each and every of the thousands of clinical trial results that are missing from the public ClinicalTrials.gov database. Universities Allied for Essential Medicines and other groups are pushing back, arguing that a federal agency with an annual budget of $5 billion can be expected to do more than post a handful of letters per year.
Both sides in this argument are missing an important point. Drug regulators in Europe have shown that there is a golden third way between inaction and legal enforcement: creative nudging.
Over the past six years, reporting rates for drug trials in Europe have shot up from 50% to 84%, despite European regulators’ lack of formal enforcement powers. In the same time period, reporting rates in the United States, where the regulator has the power to impose fines of up to $13,000 per missing result per day, rose only from 50% to 76%.
Why did trial reporting improve faster in Europe than in the United States? European officials started thinking outside the legalistic box and started getting creative.
Norman Lamb, then the chairman of UK parliament’s Science and Technology Committee, pioneered the use of creative nudging to reduce medical research waste. He wrote to all major non-commercial sponsors in the country and asked them to upload their missing results onto the European database for drug trials. The impact was as swift as it was stunning. Reporting rates, including for drug trials more than a decade old, skyrocketed and remain very high to this day – even though the recipients fully knew that neither Mr. Lamb nor the UK’s drug regulator had any powers to impose sanctions.
The European Medicines Agency has also engaged in creative nudging. Apparently, some bureaucrats decided to take data they already had – investigators’ email addresses – and do something useful with it. A few years ago, Europe’s drug regulator started sending reminder emails to investigators whose trial results were missing from the public database. The agency had no legal powers to enforce reporting, and the obligation to report results formally rested with institutions rather than individuals, so legally the reminders were moot.
Nonetheless, the move appears to have sparked productive discussions around the water coolers of many companies and institutions. Trial reporting rates, including for very old trials, increased substantially. The gains were most impressive in those countries where national regulators had engaged in nudging of their own.
The FDA should take note. In most cases, sponsors fail to report clinical trial results because they are unaware of their obligations, fail to monitor compliance internally, or lack a sense of urgency around the issue. Turning a blind eye for sixteen years and then suddenly hitting companies and institutions over the head with a big legal stick is not an effective regulatory strategy.
Instead, the FDA should first nudge the majority of players into line, and then crack down hard on the minority of holdouts who point blank refuse to follow the law.
As a first step, FDA Commissioner Robert Califf should mount his podium and publicly announce that the FDA will henceforth systematically enforce the law and impose fines. That would likely send most sponsors scrambling to review their trial portfolios, put oversight mechanisms into place, and rapidly make public thousands of clinical trial results.
Two months later, the FDA could send a friendly email to all parties that still have results missing from the public database, encouraging them to self-assess their legal compliance and follow up accordingly. Again, this would likely lead to a large number of clinical trial results being made public within a short span of time, sparing the FDA the effort of assessing most trials’ legal status itself.
Europe’s experience suggests that by combining the two high-impact creative nudges outlined above, the FDA could close most of the medical evidence gap at minimal cost, and far more rapidly than by writing one letter packed with legalese at a time. And the need to act is urgent.
Medical data that cost billions to generate are now in acute danger of becoming lost forever. A recent study looking at three years’ worth of NIH-funded pediatric trials found that half had never published results, wasting hundreds of millions of dollars; the benefits and harms experienced by the over 40,000 children who enrolled in those trials remain completely unknown. Some pharmaceutical companies have also failed to disclose the results of their pediatric trials.
Today, across all branches of medicine, large evidence gaps make it difficult for Medicare and other healthcare providers and insurers from reliably assessing whether drugs and devices are safe and effective, undermining efforts to rein in soaring treatment costs.
In recent months, Congress has finally woken up to the immense human and financial costs of continued bureaucratic inaction. Both Democrat and Republican lawmakers have pushed the FDA and NIH to finally enforce the law. A citizen petition recently filed by student activists is forcing the FDA’s hand, giving it 180 days to lay out its enforcement plans.
Over the coming months, while the agency’s lawyers mull over every word in the FDA’s formal response, its leadership should use creative nudging to get as much missing medical evidence out there as possible, as rapidly as possible.
To be clear, creative nudging is no substitute for comprehensively enforcing the law, as Congress clearly intended the FDA to do. As in every walk of life, there will always be a small minority of bad actors that will only respond to a big legal stick. But there are plenty of low-hanging fruit that the FDA can start picking today, before it starts systematically chasing down the remaining missing results one trial at a time.
Till Bruckner, PhD is the founder of TranspariMED (@TranspariMED) (no industry funding, no personal COI)
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Does this include negative or damaging trial results? With the off and on research I have done over several years, I trust no big pharma drug trials. This is one reason that at age 73 I am still avoiding taking any drugs, even OTC's are on my never use list.
Evidence distortion? To me that means that most evidence is lacking, invented, manipulated or non-existent. The near perfect scenario that the FDA proudly uses to approve drugs. Why do so many drug trials use near perfect and healthy humans when the drugs they are creating are for the diseased and ill?
After the mRNA prototype gene manipulating substance approval process, including the safe and effective mantra etched in granite, I trust none of it and never will.
Sooooo.... if these trials use public funds, why not have in the enforcement tool box the ability to claw back those funds if the trial results are not published? Money talks. That possibility would seem to be useful. Or in addition to that, release only half the funds for such trials upfront, with the rest due upon submittal. There are ways to encourage meeting the terms, and do so upfront. Transparency, no hidden weenies, etc.