From The Editor | July 9, 2018

Clinical Trials: Not Broken, But In Need Of Repair

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

Clinical Trials

We all know the days of Big Pharma companies launching billion-dollar blockbuster drugs are generally behind us. Today, novel new therapies are harder to bring to market. Trials are costly, take a long time to complete, and too many of them fail. On top of that, many of the issues companies face today are the same ones they dealt with 20 years ago.

The challenges have led Janet Woodcock, director of the Center for Drug Evaluation and Research at FDA, to remark in 2017 that the clinical trial system is broken. But if that’s the case, how do we uncover the underlying problems and bring all stakeholders together to fix them?

Doug Peddicord
A panel at the 2018 Clinical Leader Forum came together to discuss this issue. The panel consisted of Greg Koski, founder and CEO of the Alliance for Clinical Research Excellence and Safety (ACRES); Dan Milam, VP of Global Engagement for the Society for Clinical Research Sites (SCRS); Patty Leuchten. president and CEO, of The Avoca Group; Jim Kremidas, executive director of the Association of Clinical Research Professionals (ACRP); Doug Peddicord, executive director of the Association of Clinical Research Organizations (ACRO); and Robert Hardi, president of the Academy of Physicians in Clinical Research (APCR).

Koski started the discussion by noting a recent article in Fortune that discussed the problems with clinical trials. In addition to the issues noted above, it cited regulation, enrollment problems, and patient centricity obstacles.

“I read it with a sense of deja vu,” said Koski. “Articles like this have been published multiple times over the last 20 years. It’s unfortunate that the message is still there, but not much has been done to change it. What we need to do is to get a better understanding of what the real problems are and then thoughtfully come up with approaches that can address those problems.”

Patty Leuchten
But are trials actually broken? Leuchten doesn’t think so. “I had a visceral reaction when I saw that statement made by Janet Woodcock,” she says. “I have a lot of respect for Dr. Woodcock, but I don’t agree with the statement that clinical trials are broken. Over the last 50 or 60 years, since the thalidomide tragedy, one thing we have done well is patient safety. When it comes to safety, regulators are our friends.”

Leuchten is also concerned about the reputation of trials and how they are perceived by the general population. We want patients to consider participating in a trial. We also want young people coming out of our universities to consider clinical trials as a career option. Will they do so if they believe the system is broken?

“I certainly believe there are pockets of dysfunction and significant room for improvement,” states Leuchten. “But this is not a situation where trials are broken and cannot be repaired. The solution is figuring out how we can operationalize better ways to work together.”

Leuchten’s comments resonated with Kremidas. He agrees that trials are not broken. They simply need to evolve. The science we are using in trials, along with available technologies, are evolving very quickly. That means the individuals performing the trials also have to evolve.

“We now have mobile technologies that capture data from patients in their day-to-day lives, which eliminates visits to the clinic,” says Kremidas. “We see a lot happening from a technology perspective. That makes me think maybe trials are not broken. Maybe they just don’t function well in the environment we’re moving into.”

Address A Moving Target

Jim Kremidas
Another problem for the industry is that it’s always aiming at a moving target. Kremidas notes we are trying to create better trials in a space that is constantly changing. With all the change occurring, we may have forgotten about the individuals executing the trials. We still do not have a standardized way of bringing in new study coordinators and CRAs, which has resulted in a workforce shortage in those areas.

“If we want better trials, we have to do a better job of standardizing how we bring new talent into the industry, how we assess performance, and how we develop their skills,” says Kremidas. “We also have to get rid of all the variance that exists today.”

The problem may be that trials are not broken, but rather that they are from a different generation. Or as Kremidas puts it, are we trying to operate a 50-year-old jalopy on the Autobahn?

Peddicord agrees with that assessment. In fact, he takes it a bit farther. He doesn’t believe trials are broken. But for the people who matter most in trials, patients and investigators, he says it often feels like we are conducting trials the same way we did 100 years ago.

“I believe we have made progress,” says Peddicord. “We’ve certainly made real progress in the 20 years I’ve worked in the industry. But, for the people involved, it often feels like we’re taking an antiquated approach. Making progress will ultimately be about how to bring innovation to a process that has been fairly inflexible.”

Peddicord states trials today are complex, and are in need of both flexibility and simplicity. Thus far, it has been hard for the industry to attain either one. So the challenge for sponsors and CROs is how to reimagine the paradigm and move forward with truly patient-centric trials that reduce the burden on patients.

Focus On Patients and Sites

Dan Milam
Patients often travel long distances to take part in clinical trials. It’s not uncommon for patients to travel 50 miles or more to participate. Peddicord notes that is a meaningful burden and it impacts the trial process. Each time a patient misses an appointment, timelines get backed up. He believes the Uber Health app is helping patients attend appointments, but it has not yet moved into the clinical space.

“You can get your blood work done 50 miles away or you can get it done at the lab down the street,” says Peddicord. “Technology can enable a level of interoperability – the clinical trial site does not have to be the only place where patients can have an interaction. There is no reason an individual shouldn’t be getting routine lab work performed at a lab close to them.”

Another problem exists at trial sites. Research indicates between 70 percent and 80 percent of sites will never perform more than one trial. Although sites spend a considerable amount of time on monitoring, Koski notes only 30 percent of them are actually using electronic systems such as EDC and CTMS, which have been shown to improve performance by almost 60 percent.

“I have worked in the clinical space for more than 20 years,” says Milam. “The challenges we faced back then are the same challenges we face today, but the growing complexity of trials has amplified those challenges. Trials are more complex but the reimbursement amount for site visits has gone down. That creates a financial challenge for every site.”

With more complex and focused trials, patient recruitment becomes more difficult. Milam believes including sites earlier in the protocol development process would help. In theory, every protocol works. But at the site level, they may not. Communication must improve between pharma and sites, so feedback can be given on why a protocol would or would not work.

Certainly the large number of sites performing only one trial can also be tied back to investigators. Hardi notes the system is not broken; it does exactly what it was designed to do. However, he calls the trial system Byzantine, and the Byzantine Empire came to an end in 1453. Payments might be a way of bringing trials into the modern age.

“Little things do count,” says Hardi. “There are some who say you cannot reimburse patients and investigators for trial participation because it corrupts the study. That is absolutely not true. There are a lot of little things you can do to make your patients and investigators happy.”

“Investigators need to be asked to participate in a trial, but don’t ask them to do it for free,” says Hardi. “There are people who design trials and get nice reimbursement for doing so. But oftentimes, the investigators performing all of the work are never told the outcome of a trial, they don’t get any feedback, and they don’t get a penny for their work. That’s not a sustainable model. One reason investigators do not perform more than one study is they lose money doing it. By the time they learn how to make money overseeing a trial, they have already ceased to perform them.” 

Start With The Low-Hanging Fruit

With the many problems needing to be fixed, where do we start? Koski asked panelists for their thoughts on the easiest problems we can start to fix immediately. 

Leuchten mentioned technology adoption. When adopting new technologies, she notes pharma companies have to be in two places at once. They have to be as functional as possible in the present while also being poised to be successful in the future.

“One of the things Avoca, TransCelerate, CTTI, and others are doing is driving greater efficiency, higher quality, and mitigation of risk through the sharing of best practices,” says Leuchten. “We are also pushing practical tools, templates, and leading practices so companies can have that as their foundation. We hope to enable them to be poised to explore clinical trials of the future and virtual trials, because that’s where the industry is going.”

Others noted getting back to basics and addressing the fundamentals of clinical trials in a more efficient manner. There has been a movement towards clinical research as a care option, and it now seems to be happening via electronic health records. In some areas, we may just need a better implementation pathway. But the next step involves taking action and having the courage to make change. That is where many companies will struggle.

“As an industry, we often seem to move at a glacial pace,” adds Leuchten. “I do see some pockets of success, but real change will never come about as quickly as we hope it will.”