Next generation feasibility assessments

By Beth D. Harper

Admit it. You know that sending out site feasibility surveys doesn’t work to secure high performing investigative sites for your trial but “this is the way it’s always been done.” In this article we’ll explore why investigative site surveys are not predictive of actual site performance and what you can do to transform your feasibility assessment process to improve site selection and study execution.

A Flawed Process

The American Heritage ® Dictionary defines feasible as:
•    Capable of being accomplished or brought about; possible: a feasible plan.

A long standing clinical research industry tradition has been the use of site surveys to conduct trial feasibility assessments as part of the investigative site selection process.  With some 90% of the clinical trials failing to meet their enrollment timelines and <10% of the sites actually delivering the number of patients they project in the feasibility survey, it begs the question of why we continue to follow a flawed process?  Figure 1 highlights some of the common reasons why the typical approach doesn’t work.

Reasons why the typical feasibility assessment process fails:

•    Protocol-specific, successful site characteristics are not defined up-front and therefore not systematically addressed in the feasibility assessment process
•    The questionnaire doesn’t ask questions that really drive enrollment and execution success
•    The investigator is rarely involved in the feasibility assessment process
•    Sites don’t systematically evaluate the protocol and rely on sponsor  / CRO questionnaires to drive their review
•    Feasibility assessment is subjective in nature and not objective or  “evidence based”
•    Enrollment validation activities are not performed to confirm enrollment potential
•    Feasibility assessments are based on the protocol synopsis or draft protocol and not revisited when final protocol and budget are available

Given the criticality of identifying sites that are truly capable of being able to execute a specific clinical trial on time, within budget and within the high degree of quality our industry demands, we need a dramatic transformation of our feasibility assessment process. 
Feasibility Fixes

A “next generation” feasibility assessment process combines both quantitative and qualitative evaluation of enrollment potential and a systematic and structured approach to uncovering the factors that will impact seamless study execution and the characteristics that will define a high performing site for the specific trial.  It proactively identifies and highlights challenges and risks and focuses on developing early mitigation plans for the risks.  It involves a dialogue and discussion with all of the relevant stakeholders about what factors can make the study more likely to enroll and retain subjects and deliver timely, quality data.  A “next generation” feasibility assessment process shifts the emphasis from a static site survey to a conversation asking the right questions, of the right individuals, in the right format at the right time.

Rather than asking generic and closed questions such as “are you interested”, “can you enroll 6 patients in 6 months” and “what is your typical IRB / IEC approval timeline”, the new process prompts an honest discussion with the investigator, research coordinator and relevant research staff about their interests, motivations, concerns and study implementation plans.  It strives to uncover what each site will need and which factors can be generalizable to support all sites participating in the trial.  In other words, what is needed to make the sites capable of accomplishing the study or making flawless study execution possible.  The transformed process helps sites to “fail fast” and quickly rule out their suitability for study participation before all parties invest precious time, energy and resources to initiate a site that enrolls few or no subjects and does nothing to further our understanding of the safety and efficacy of the investigational product.

Lastly, a “next generation” feasibility assessment process is one that is evidence based, particularly when it comes to validating a site’s enrollment potential.  Not only is the process of reducing a site’s enrollment estimate by 25%, 50% (or what other factor you prefer) ineffective, it contradicts the spirit and intent of Section 4.2.1 of the ICH Good Clinical Practice Guidelines which clearly advocate for evidence of enrollment potential (Figure 2).

ICH GCP Guidelines

4.2.1 The investigator should be able to demonstrate (e.g., based on retrospective data) a potential for recruiting the required number of suitable subjects within the agreed recruitment period.

In this era of technology, the opportunity to leverage electronic medical record systems for detailed quantitative analyses of inclusion and exclusion criteria creates efficiencies in an otherwise labor-intensive process.  Regardless of the availability of technology, sponsors and sites must invest time up-front to evaluate their potential and willingness to enroll subjects from within their own practice and realistically determine what the conversion ratio from identified to randomized subjects looks like.  This will drive the site’s resource plan as well as highlight the need for an external study awareness and education effort to supplement enrollment from external sources of subjects.   This effort, combined with a proactive recruitment action plan for how they will reach out to the healthcare community and general public to build study awareness will ensure a seamless translation of the feasibility analysis work into effective study implementation.

Just Do It - Differently

Next time you start your feasibility assessment process, your team starts to develop their feasibility questionnaire or you hit the send button on your site e-feasibility survey, take a moment to think about how predictive your last site surveys were:

•    Did the sites deliver as promised? 
•    What did you learn over the course of the last study that you wished you had asked earlier on? 
•    What did the high performing sites have in common?  
•    What types of interventions or rejuvenation efforts did you have to implement and could you have pre-empted this need through a different discussion with the sites?

Challenge convention and resist the temptation to do it the way it’s always been done.   Whether it’s calling up a few sites and asking their impressions of the study executability, conducting a site selection strategy meeting with your team to proactively define the “must have” site selection criteria or giving your site more time to conduct a sample chart review, just do it differently this time.  You’ll be pleasantly surprised with how a few fixes can have dramatic results.

Interested in learning more about how to optimize your protocol and transform your feasibility assessment process?  Please contact us:  information@centerphasesolutions.com. We are on a mission to go from flawed feasibility to flawless execution!

Biography

Beth D. Harper is a world-renowned expert in clinical development, with more than 25 years of experience in addressing the persistent challenges of the clinical trials process. During her career, she has provided extensive training and consulting services to enhance the clinical performance of biopharmaceutical companies, sites, CROs and SMOs. Before joining Centerphase as Chief Clinical Officer, Ms. Harper served as President of Clinical Performance Partners, Inc., a clinical research consulting firm focused on improving patient enrollment, site performance and sponsor-site relationships.  She is currently an Adjunct Assistant Professor at George Washington University’s School of Medicine, with more than 20 articles published on this topic.  Ms. Harper has a B.S. from the University of Wisconsin and an MBA from the University of Texas.

About Centerphase Solutions, Inc.

Centerphase is a new technology-enabled services company focused on leveraging electronic health information and innovative operating procedures to accelerate the clinical development process. With over 60 years of experience in the biopharma industry, we have experienced first-hand the consequences of poorly designed trials.  At Centerphase, we have drawn from these real-world learnings to directly take on the root causes plaguing the clinical trials process.  Centerphase was started through a unique collaboration between the founders of Merck’s venture capital group and the renowned Mayo Clinic.