Big tent science: new ideas about clinical trials

What’s big tent science?

As a stem cell scientist I hear all the time about how the pipeline from the lab to the clinic is incredibly slow and terribly inefficient. Meanwhile millions of people have conditions that the current state-of-the-art medicine cannot effectively treat. Somehow we need to make a fundamental change to improve this process. I think one aspect of this change is a new kind of team effort whereby MDs, PhDs, funding agency officials, regulatory officials, and critically patients are brought together earlier in the process and follow it through each step. This is big tent team science.

From the time a scientist identifies a potential target or the basis for a new drug in the lab until a patient receives a therapy based on that finding, assuming success clinical trials, is often mentioned as 25 years. Further, we hear that >95% of the time potential development of such possible therapies fail. Often times promising drugs also are dropped from further investigation not for scientific reasons, but rather for financial ones.

These are roadblocks to making new therapies that are urgently needed, but how do we overcome them without compromising our standards for safety and efficacy? We can see how dangerous it is with stem cell tourism if the current system involving the FDA is bypassed by people trying to make money from patients. Ideally there should be a way to make clinical trials faster, but it is not clear how to speed up the process without in parallel increasing risk. One inherent obstacle to speeding up trials of drugs for human use is that they must be tested in people and the trials must allow for enough time to study safety and efficacy in a manner that has relevance to the timeline of potential future patients who would receive such drugs. Thus, the timeline for trials has to be measured in years, not in shorter increments such as months. I think it is crucial that patients and patient advocates play a role in helping scientists, doctors, and policy makers understand and balance the importance of risk, meaning the potential for harm from side effects to patients. For certain conditions, such as those that cause lifelong disability of have extremely high mortality rates, perhaps a higher level of risk that might accompany a faster clinical trial process is acceptable. To some extent this acceleration can happen even today, but not to the extent that many patients view as essential.

Beyond time, of course success rate is crucial. Speeding up the clinical trial process will do no good, if the failure rate is still in the 90+% range and it is even possible that a faster clinical trial process will increase the failure rate. That a key question is how can we use creative ways to boost our success rate at least into the double digits in terms of how often candidate drugs become realized therapies? Do we need to change our model system of how we develop candidates in the first place or somehow include a filtering process to make our pool of candidates stronger?

One potential way to help both speed the process and increase its efficiency is to take a somewhat of a novel team approach whereby we bring together MDs, PhDs, and patients along with funding agency officials and regulatory officials earlier on in the process. In particular I think there is right now an enormous distance between PhDs and patients that is harmful to the process. One reason for this distance is an illogical cultural aspect of science whereby most PhD scientists avoid interacting with people who are not scientists such as patients. We need to change that as patients and patient advocates have a tremendously powerful perspective that PhDs and also MDs to some extent cannot simply try to imagine in their own minds.  In addition, PhDs have a unique perspective that is important as well that oftentimes MDs may not inherently bring to the table themselves. For example, PhDs view clinical trials from their own perspective as experiments and are not surprised when they fail relatively often because that’s simply the way it is with experiments.

We hear a lot of talk about team science these days, but the biomedical team I envision is not just a grouping of different scientists, but also including non-scientists. I call it the “big tent” approach to team translational and clinical science. Nothing is a panacea and improving the clinical trials process is no easy task, but I think working together we are more powerful than working apart.