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While some countries are more progressive in approaching this challenge by virtue of mandatory, free of charge, molecular testing on all patients, this varies greatly in other countries based on institutional policy and insurance reimbursement.
EGFR mutations. BCR-ABL translocation. 17p deletion. KIT and PDGFRA mutations. HER2 amplification. KRAS mutations. ALK translocation. All of these once unfamiliar terms are now commonplace in the landscape of oncology research, creating an exciting time in the era of personalized and targeted therapies, and inversely creating challenges in enrolling these narrow subsets of patients into clinical trials.
While some countries are more progressive in approaching this challenge by virtue of mandatory, free of charge, molecular testing on all patients, this varies greatly in other countries based on institutional policy and insurance reimbursement. Given this current and not easily modifiable fact, how can sites, sponsors and CROs partner more effectively in enrolling clinical trials in these targeted populations that have unmet needs and typically a poorer prognostic outcome?
While there is no single “magic” bullet for being able to enroll well into targeted patient population trials, a thoughtful, well executed plan at the beginning of the study is critical to ensure alignment and understanding of the inherent challenges and to partner effectively to set realistic expectations. Prior to starting the study, the following tenets should be applied:
Know thy competition: While competitive landscapes are assessed differently for targeted therapies, there will still be an impact on site resources, as well as an enrollment impact for scientifically interesting therapies.
Know thy math: Too often, when feasibility assessments are performed, the questions are not deep enough. It should never be “how many patients do you think you can enroll,” but a “how many patients do you SEE?” This must then be converted to the percentage of patients that are known or suspected for a potential target, the knowledge that some patients will elect to not participate or be excluded for other reasons, and a subset of sites that will not enroll fully or well due to a variety of reasons. This should be considered closely when assessing how many sites will need to be active to meet enrollment timelines.
Know thy target: An overarching tumor or disease type cannot be extrapolated into a meaningful assessment of potential enrollment rate at a site. Working hand in hand with site staff is an important step in understanding “a patient is not a patient is not a patient,” meaning an inverse funnel approach should be used: Triage from the most “rare” targets to the least. Chances are, many will fall out into broader studies once the triage is completed. Of course, this is always balanced by what is most beneficial in the opinion of the investigator for the patient. This can be a critical, but often forgotten step.
Love thy lab pathology neighbor: Too often, these are neglected groups without the realization of the amount of work needed to process samples. This is magnified with targeted therapies due to the number of patients that need processing to identify an appropriate candidate for the protocol
Thou shalt reimburse for screen failures: Most sponsors are sensitive to this, however it’s important to not only reimburse for screen failures, but to also ensure that the startup costs are included to offset any effort in the event the site cannot enroll due to incidence.
Be kind to thy study staff: Enrolling into a targeted study is a lesson in patience and perseverance. Often times, the staff will need reminding of why this study is important, and that the efforts and patients identified as acceptable are in line with the theory or known incidence rate of the target. This can become particularly acute if the site is the unlucky recipient of many patients that are not eligible.
Thou wilt communicate appropriately: Communication is a conversation versus a one way flow of information. This includes study updates, encouragement by the sponsor and CRO partner, transparency in how patient flow works at a given institution, and the effort and commitment behind a given study. While care should be taken not to over-communicate (from a CRO and sponsor standpoint), there is the balance of understanding how things are working at the site, effort expended, ways that the CRO and sponsor can better partner, as well as an understanding of what may not be working well in the protocol so modifiable criteria can be considered for amendment.
Share the news: Patients are increasingly computer savvy and sites are often looking for institutions that can offer cutting- edge therapies. Patient advocacy groups, referral networks and announcements at major meetings are all ways to socialize the news and the science. We recently asked a key investigators - who is not in a major city - how he always recruits so well into the studies we place with him. His response was quite simple, “My colleagues in the other institutions know the work I do and I pick up the phone when they call me”. This back to basics approach of networking, relationship building and sharing what you have with others works well for this investigator.
We are indeed in an exciting time, personalizing medicine with increased frequency. History is unfolding before us, and there is enthusiasm and confidence in the difference we can make in our patients’ lives if sponsors, CROs and sites work together. It will require additional innovation, as techniques for identifying and data needs to be more readily accessible, but we are well on our way to bringing additional treatments for patients in need.
C. Meghann Howland, Executive Director, Global Early Phase Oncology, INC Research