On March 14, outgoing FDA commissioner Scott Gottlieb chided pharmaceutical companies and clinical research organizations (CROs) for being slow to embrace innovations in clinical research, even when the FDA sanctions those innovations. “The business model adopted by the clinical trial establishment just isn’t compatible with the kind of positive but disruptive changes that certain innovations can enable,” he wrote in a statement.

The data back him up. Use of innovative designs such as adaptive trials, patient-centric trials, precision medicine, and real world evidence is vanishingly low, ranging from 0.3 to 15% for Phase II and III trials. These innovations can increase the likelihood of launch for new drugs by 10-21%.

Why, after 15 years, is pharma still struggling to adopt innovative trial designs? There remain many obstacles, including:

•   Lack of sufficient investigator, site, and patient input

•   Poor operational standardization of data and protocols

•   Negative perceptions of pharma’s approach to innovation among payers and patients 

•   Risk-averse, “adoptaphobia” behavior

FDA keeps churning out guidelines for innovation 

To foster innovation, the FDA recently offered a slew of initiatives. The agency’s Master Protocol guidance (September 2018) allows for the evaluation of multiple investigational drugs, disease types, or patient populations under a single clinical trial structure. (This is not new: the first “basket” trial, conducted by Novartis, tested imatinib mesylate in five different types of cancer in a single Phase II trial). A pilot program for Complex Innovative Trial Designs (August 2018) promotes the use of seamless trial designs, Bayesian models and other advanced statistical approaches. And Gottlieb’s March 2019 press statement was a rollout for the FDA’s new guidelines on clinical trial enrichment strategies and risk-based monitoring-both practices key to precision medicine.

However, guidance documents are not the whole story. For example, the FDA’s Master Protocol guidance suggests that sponsors use independent data monitoring committees (IDMCs) to conduct pre-specified and ad hoc assessments of endpoints and recommend protocol modifications. However, research has shown that there no standards for IDMC operating procedures, qualifications, and training.

How can pharma address obstacles to innovation?

Despite operational obstacles and low adoption rates, the industry has chalked up a few successes with innovative approaches. Effective strategies strike a balance between adopting innovation and mitigating risk. Companies can: 

•  Adopt clinical trial data standards and agreements proposed by organizations such as TransCelerate

•  Provide patients with a virtual simulation of the clinical trial experience and offer logistics support to facilitate access to clinical trial sites

•  Utilize digital health apps that combine on- and off-site data to boost patient compliance and engagement in the process

•  Engage with the FDA early and often, especially if the development plan involves using novel biomarkers, non-traditional clinical endpoints, or other innovations

For its part, the FDA can continue to support innovation by sharing concrete examples of how sponsors and industry have worked together to solve problems and striving for better cross-divisional collaboration, standardization, and communication on crucial drug development issues. 

Venkat Sethuraman, Sharma Ramanathan Deva Devesa, and Arvind Chavali, all affiliates of ZS Associates