For years, Randomized Controlled Trials (RCTs) have been the gold standard for assessing the safety and efficacy of investigational new drugs. These trials are considered the most effective at overcoming bias and yielding high-quality evidence because patients are allocated at random to receive either the study drug or a comparison/control product. Patients are unaware of which group they are assigned to, and all other variables are kept constant.

However, there has been some push back against this type of clinical trial in recent years, and, in June of this year, The New York Academy of Sciences held a meeting to discuss the future of RCTs. The meeting brought together influential players from pharma, the FDA, patient advocacy groups, government health organizations, and educational institutions including Harvard and Duke.

A number of different opinions and perspectives were shared, which allowed for open and frank discussion about the benefits and drawbacks of using RCTs.

Many voiced concerns with the current RCT framework. Some believe that the cost and time associated with conducting a RCT is too burdensome for drug companies. Companies often have to spend a considerable amount of time and money on finding a big enough pool of patients to make the trial results meaningful, managing the multiple trial sites that are necessary to reach the patients, sourcing and delivering comparator products, and generally overseeing the whole trial process. Arthur Caplan, from the NYU School of Medicine, argued that many companies don’t have the resources available to commit to such a costly and timely expense, especially if they have multiple drugs in their pipeline.

Others argued that an inherent flaw with RCTs is that the eligibility requirements are often too narrow. This means that large numbers of patients are excluded from the trial. Not only does this result in patients lacking access to treatment, it could also mean that the results from the trial do not reflect how the drug would work in the larger patient population.

Another issue raised was the morality behind using placebo products, especially in the rare disease space. Although comparison to a placebo may be the best way to prove efficacy of a new product, patients enrolling into clinical trials are often desperate for treatment and consider the trial drug to be their last hope. Is it fair, then, to give these patients hope that they may be receiving a potentially life-saving drug only to turn around and give them a sugar pill or another drug which has already proved ineffective for them. Physician, Marcia Angell, argued that the industry’s strict adherence to the RCT framework often comes at the expense of compassion for patients, which results in patients feeling as though they are guinea pigs.

However, others raised arguments in favor of continuing to use RCTs as the default design for testing new drugs. Barry Gertz, from Clarus Ventures, for example, claimed that, despite the potential burden involved in a conducting RCT, randomization is the most effective way of reducing bias. He argued that the societal burden would be far greater without randomization, and that, if companies don’t test drugs with adequate rigor, new drugs can be seen to be a lot more effective than what they actually are. Gertz used a drug tested for severe hypertension as an example of this. He claimed that, after non-randomized clinical trials, the drug was deemed to be a miraculous new treatment option for patients. However, subsequent RCTs proved that it was actually no more effective than treatments already on the market.

In the end, it seemed that most meeting attendees agreed that the RCT has its place in research and development efforts, but that industry should try to evolve and introduce new, diverse measures for testing drugs alongside RCTs. Jane Perlmutter, from the audience, declared that there is no need to lower the bar when it comes to testing new drugs. Instead, she argued that we need to come up with more innovative approaches that allow a greater number of patients to receive access to investigational products when they need them most. This could be done by conducting pragmatic trials, which more accurately mimic drug use in the real-world setting, or by allowing tentative FDA approval using an intermediate or surrogate endpoint, as long as later tests are conducted to confirm the findings.

To learn more about what was discussed at the meeting, and to gain a better insight into the arguments both for and against RCT, click here to access the full meeting report.