By far, the biggest challenge for clinical trials is patient and volunteer engagement and retention. Most trials are not completed on time due to a scarcity of participants, which slows up research and has financial implications. In the second of this three-part interview article series Dave Selkirk (CEO and founder of Whitechurch Pharma & Biotech Consulting), a pharma industry veteran with three decades of experience considers ways of overcoming these obstacles.
I think the pharma industry has been trying to improve the uptake of volunteers for many decades. One of the ways they communicate about clinical trials is a website called clinicaltrials.gov. Essentially every clinical trial happening in the world gets listed there. There are many tens of thousands of clinical trials listed, but unfortunately, the information is sometimes incomplete or partially incorrect. It is also quite scientific and not necessarily written for the layperson and so deciphering the meaning of some of the information can be challenging for the average individual. And, of course, it is all written in English as well. If English is not your first language, then accessing that information is a challenge.
There have been moves to make sure that publicized clinical trials are at least visible to academic and scientific communities. However, reaching healthy volunteers and patients is still a challenge, and the industry doesn't have a good solution. We still rely mainly on clinicians who have relationships with their patients to bring in people with specific disease indications.
For the first-in-human studies, we rely on what we call phase one clinics or clinical research units that have databases of healthy volunteers who have volunteered in the past. They are called upon to volunteer again. But the more diversity you can have in the individuals coming into a trial, the better. You don't always want to have the same types of phenotype and genotype. Diversity is a strong need that we have to increase.
I wonder if one of the reasons for a dearth of volunteers is a lack of knowledge about what's involved or nervousness because of a news story about someone being taken ill during a trial.
In today's society, sensationalism sells, and what is dramatic and what is eye-catching, or headline-grabbing is put out there in a much more intensively publicized manner. I would guess that at any one point in time, there are tens of thousands of healthy volunteers involved in trials daily, and for the most part, all of those patients are absolutely fine.
That type of information never gets reported—the tens of thousands of individuals who are completely fine. But every once in a while, you'll hear about a debilitating event in a healthy volunteer during an early phase trial. And those events are highly publicized.
So, you may hear that somebody received medication and maybe the physician got the dose wrong, or the pharma company miscalculated the pharmacokinetics and dynamics and instructed the investigator to give a dose that was not appropriate. Perhaps there was some impact on liver function or lung function or another organ system. Those things get publicized immediately, but you don't hear the context. What happened with this one individual is tragic and should not be minimized, but it is the first time it happened within the last 50,000 volunteers. That part, you don't hear.
What the layperson understands is, "Didn't I hear six months ago that a healthy volunteer had a problem, and now I'm hearing it again? Wow, I've heard two reports of this type of thing this year!" But it's not contextualized. It's two out of hundreds and thousands. You're much more likely to be hit by a car crossing the street going to work than you would be damaged or hurt in clinical trials.
How do you hope CenTrial will help address the challenge of insufficient volunteer numbers?
CenTrial is addressing the biggest challenge that faces clinical trial conduct and pharmaceutical biotechnology therapy development on our planet. We've talked about how trials can be done more effectively, quickly, efficaciously, and safely. None of that matters if you don't have the healthy volunteers and don't have the patients to participate.
The CenTrial platform is promoting clinical trials as a wellness and treatment option and that is an important step forward because the entire world needs to be aware of this. It helps connect the world's people with the world's clinical trials, which is exactly what the industry needs.
Any technology platform, communication methodology or other tools that can be used to make sure the general public is aware of clinical trials as a treatment option and a scientific research option are very important. We need to make sure they're abundant and available en masse.
Are there any other challenges faced by pharma companies when developing drugs?
Yes, absolutely. One of the other issues over the past decade, perhaps two decades now, is that protocols are becoming increasingly complicated. More and more measures are being written into the protocols, exploratory types of analyses.
For example, when a lot of immune-oncology therapies were introduced, you would collect blood because you wanted to do an entire screening panel of everything that could be happening. You collect perhaps urine samples, fecal samples, telemetries, scans, ultrasounds, lots of imaging, and just all kinds of things to give you as much of a complete picture as possible. But in fact, the protocol's primary efficacy variable was to measure progression-free survival or one of the other recist (response evaluation criteria in solid tumors) criteria that exists in oncology. So that's a very specific endpoint that requires only one type of measurement, but you are doing hundreds of other measurements just because.
This has become much more standard, and it adds an enormous burden to both the patient and the clinician. From a patient's perspective, they're being poked and prodded and asked to record information with electronic diaries or wearables, record their symptoms, record their side effects, and record how they feel. All of these additional requests made of patients and clinicians take their time, deviate from the standard of care, impact people's quality of life, and the clinicians' ability to focus on the key endpoints.
However, the industry has started to take a step back because, as you can imagine, the other impact of all of this level of complexity and layering is, of course, cost. There is a movement to try and scale back that level of complexity. And I think that's appropriate to focus on the primary variable and the second variable, which is generally an efficacy and safety type variable. Then really reduce the number of other variables that are being collected and measured. It makes it easier for everybody to conduct trials.
There is a delicate balance between what's an appropriate level of exploratory outcome collection versus you've just got too complicated, and now the study is too burdensome for everyone to execute.
While the industry grapples with the issues, one promising advance has emerged in recent months. The rapid development of COVID-19 vaccines could lead to significant shifts in the clinical trial landscape. In the final article of this three-part article series, Dave Selkirk considers how this might impact the future of clinical trial execution.