You have a compound for the treatment of NASH. Now what? (Pt. 2 of 3)

This is part 2 of a 3-part series.

You can find part 1 here and part 3 here.

Series Overview

One primary barrier to getting new drugs to market is the inability for sponsors to enroll their clinical trial. With more than 70 investigational NASH drugs in development across more than 60 sponsors, the next 5 years* will see the need for at least 30,000 patients to enroll in clinical trials. The success (or failure) of your compound literally depends on meeting your enrollment milestones.

In this series, Continuum Clinical will pull from its more than 25 years of clinical trial enrollment experience to discuss the NASH patient journey, educational and awareness opportunities—including those specific to underrepresented patient populations—and other challenges associated with reaching and motivating this unique patient population. Ultimately, we will provide clear insights about what is necessary to help sponsors meet or beat their enrollment milestones for NASH clinical trials.

Part 2: The Barriers to NASH Recruitment and How to Overcome Them

As if the patient journey weren’t complex enough, now comes another challenge: randomizing NASH patients for clinical research.

As previously discussed, a NASH diagnosis—and the unexpected confusion and grief that come with it—is unique. Consequently, so too are the barriers that sponsors and CROs will face with NASH patient recruitment and enrollment.

The numbers tell the story. Based on the number of Phase II and III trials actively recruiting or pending recruitment, the next 5 years will see the need for at least 30,000 randomized NASH patients.¹ Right now, it’s estimated that as many as 30 million Americans may be living with NASH, but only 180,000 have been diagnosed.² Given that the average research participation rate is around 15% of a given diagnosed population³—and coupled with the estimated 80% screen/fail rate for this condition—that means the 180,000 diagnosed patients will translate into only 3,000 randomizations.

Making enrollment even more difficult is the fact that only 2% of the population is aware that the condition even exists.⁴ And getting people to adopt new therapies—or participate in the research needed to find new therapies—is dependent on them being aware that there is a problem to begin with. In other words, awareness of a condition naturally precedes adoption of its treatment. It’s exponentially more difficult to enroll patients in a clinical trial for a condition they’ve never heard of.

It’s safe to say that clinical trial enrollment for NASH is going to pose challenges unlike anything we’ve ever seen before. Here are some that concern us the most:

First, there is no “standard” NASH patient: these patients look and act differently from one another. There is no universal patient experience, which means that identifying patients for education or trial outreach will be different than with most other high-prevalence conditions where the diagnosis pathway is relatively universal. And speaking of diagnosis, an actual NASH diagnosis unfortunately requires patients to suffer through invasive and potentially dangerous liver biopsies—yet less than 20% are actually diagnosed with NASH due to its asymptomatic nature.⁵

Second, as previously mentioned, there is little to no awareness of NASH as a condition. Complicating this even more is the fact that there’s little awareness or concern for liver disease in general—even among those most at risk. In fact, in a recent national survey of 450 at-risk people, only one respondent mentioned liver disease as a concern.⁴

And finally, sites will struggle to recruit from within their practices because the diagnosis rate is so low. Site burdens will continue to grow as more trials enroll and the competitive landscape continues to expand.

So what can we do?

First and foremost, we have to acknowledge and get a handle on the challenges we are facing.

In patient recruitment and retention planning for clinical trials, it is important to identify barriers to enrollment and retention. An immediate need will be finding a remedy for the invasive biopsies that the FDA requires for definitive diagnosis in NASH studies—a reliable non-invasive approach is needed to identify potential NASH patients for early screening and treatment. Many researchers are investigating biomarkers that will be as predictive, if not more so, than invasive liver biopsies.⁶ But this is a longer-term solution, and clinical trials are enrolling now. We need patients quickly, which means we need a way to address the enormous gap between the diagnosed patient population and the number of patients who will be needed to fill these trials. That’s where a robust patient recruitment program must be implemented.

In lieu of—or in addition to—an unbranded disease awareness campaign (which we believe pharma should prioritize in partnership with patient advocacy groups), we would recommend incorporating disease education into clinical trial recruitment outreach materials. These outreach materials have to be part of a robust patient recruitment campaign. Sites simply cannot fill these trials on their own, so sponsors and CROs are going to need to prioritize outside patient recruitment experts in order to meet their enrollment milestones. Developing effective recruitment materials will require a wide range of insights, as well as prioritizing and investing in diversity and inclusion initiatives through patient advocacy groups and community events.

Of course, educating the NASH patient and building awareness are just small parts of the overall picture. True success will only be achieved when a complete range of solutions can be utilized to include site management, media planning, data analytics, patient experience, patient advocacy, and diversity and inclusion efforts.

We believe this will be especially crucial with Hispanic and Latino patients—who not only have a higher risk of developing NASH but also have also shown an increased interest in NASH clinical research.⁴ That means that this isn’t about doing just any type of campaign. It’s going to require unique, strategic, and creative campaigns that place a prioritization on a population typically underserved by clinical trials. Directly engaging patients locally through educational and community events is critical to connect with patients both before and after diagnosis. Community-level engagement, especially important to minority populations, will ensure NASH patients will receive education and information at the right time in their journey and can make recruitment campaigns more effective.

Yes, these challenges are enormous. But with the right strategies and messaging, we can overcome them through smart patient recruitment.

^References:

^{1) Recruiting, not yet recruiting, and recently-completed industry-sponsored Phase 2 or Phase 3 trials in NASH. Available from: http://Clinicaltrials.gov. Accessed May 28, 2019.}

^{2) Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology. 2013; 57(4):1357-65.}

^{3) 2015 – 2016 Global Participation in Clinical Trials Report. US Food and Drug Administration. Available from: https://www.fda.gov/media/106725/download. Accessed May 28, 2019.}

^{4) Continuum Clinical. 2019 Patients at High Risk for NASH Insights and Awareness Survey; 2019. [Survey results pending online publication].}

^{5) Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64(1):73.}

^{6) Li Q, Dhyani M, Grajo JR, Sirlin C, Samir AE. Current status of imaging in nonalcoholic fatty liver disease. World J Hepatol. 2018 Aug 27; 10(8): 530-542.}