Following our participation in Clinipace’s Boosting Enrollment in Oncology Trials webcast, we wanted to share some of our thoughts on the need for protocol simplification especially in early phase oncology trials, as well as field some related attendee questions
In our experience, complex and burdensome protocols may decrease oncology trial enrollment, increase cost and impact trial quality. Ken Getz, Director of Sponsored Research Programs & Research Associate Professor at the Tufts Center for the Study of Drug Development, recently examined this issue at the 2013 EURO DIA meeting. He shared the following data based upon a 2012 analysis of typical trial protocol.
As it relates to protocol amendments:
- 43% of protocols have an amendment before the first patient is ever dosed at a cost of $500K in direct costs and 2 months delay
- 40% of the amendments are avoidable
To increase both patient enrollment and retention, we recommend simplifying your trial design before trial start-up begins. We understand how temping it is, especially early in a Phase 1 program, to throw everything into your first trial, including the kitchen sink. However, we have to consider the patient and their ability to enroll in such a trial. During the webcast, we discussed the following recommendations for simplifying trial design and avoiding protocol amendments:
- Involve study coordinators or others with an understanding of patient experiences in a clinical trial during protocol development
- Choose to collect only essential data – and decrease the number of CRF pages
- Start your study with a FINAL protocol so amendments are not needed until a significant change is required
In addition, we wanted to provide feedback on two questions posed during the webcast.
Often during the feasibility phase not all of the information is available to make an informative decision. (i.e 12 hr pk draw). Sponsors also need to provide more detail up front information. Have we addressed those concerns in the suggestions above?
We agree that it is difficult for a site to make an informed decision about participation and enrollment estimates without the necessary information to do so. Feasibility needs to be conducted using a near final protocol or a robust synopsis. Enrollment estimates should also be done on a worst-case basis, e.g. a 12 hour PK versus 8 hour so that we are considering patient willingness to participate. In addition to the near final protocol, laboratory and pharmacy manuals may be helpful for the site’s review.
Often IRB is strict about putting benefit of drug in the protocol or ICF. Any suggestion on incorporating the benefit of the study drug?
IRBs are strict regarding benefit of a drug in the ICF in order not to have the ICF be coercive to the patient to enroll. Especially in early phase trials the only benefit is the care or possibly therapy provided at no cost to the subject, and there is no clinical benefit. The only way to show benefit to patients is if there is data showing benefit (CR, PR) in previous studies.
IRBs exist to protect the study subject and the process of informed consent must ensure the patient knows of the risks related to participating in a trial. Clinical trials are testing new therapies and therefore the ICF cannot promise anything that has not yet been proven. The ICF can include the data that is known about the compound (or in the case of an approved comparator drug, the details about the comparator) from preclinical or other trials, but the ICF also states the compound is not FDA approved.
This blog post collaboratively written by Chris Mackay, Project Director, Early Phase Pharma, University of Kansas Cancer Center and Clinipace’s Barb Geiger.