According to the Merriam-Webster dictionary, one of the definitions of the word strategic relates to something being “of great importance within an integrated whole or to a planned effect.” If we think about the subject eligibility assessment process, the planned effect, or result, is the enrollment of subjects who meet all inclusion criteria and don’t have any of the exclusion criteria. In other words, it’s the enrollment of subjects who comply with the protocol requirements. The integrated whole refers to the fact that the entire list of eligibility criteria can be segmented into two parts — the evaluation of the eligibility criteria that a site can evaluate pre-consent vs. the criteria that can only realistically be determined once the subject signs the informed consent document and formally undergoes the screening evaluation. Of great importance is how the criteria are segmented to allow for both efficiency and accuracy in the process. Collectively, I refer to this as “strategic patient or subject screening.”
Why is a more strategic approach necessary and beneficial?
First and foremost, as already mentioned, the strategic approach ensures that enrolled subjects comply with the protocol. This protects subject safety and ensures data integrity, the cornerstones of Good Clinical Practice (GCP). From a resource and efficiency perspective, strategically segmenting the eligibility criteria into pre-screening and screening criteria, allows investigative sites to better distribute the workload across clinical research professionals of varying skill sets. For example, a medical assistant may be able to quickly work through a series of pre-screening criteria (via chart reviews or database queries) to evaluate prospective candidates, leaving the more in-depth and time consuming subject screening to higher skilled (and more expensive) resources such as nurses, physician assistants and physicians. From a business and financial perspective, understanding how the inclusion/exclusion criteria can be segmented can influence the evaluation of clinical trial budgets. This ensures that proposed patient recruitment and “screen failure” payments are commensurate with the work effort required to pre-screen and screen subjects for a given trial.
What does this look like in practice?
Consider that a typical protocol has 35 eligibility criteria.1 The way the criteria are listed within the protocol, however, are often somewhat random, usually with the first inclusion criteria being listed as the age requirement. The second criteria might list the core diagnosis for the indication of interest, the next criteria might be related to birth control requirements and the following criteria, related to an inclusionary medication or laboratory requirement. In other words, the typical protocol doesn’t organize or group the criteria into meaningful categories that would enable a site to efficiently assess the various criteria “buckets.” Further, the criteria are rarely segmented into criteria that can be determined pre-consent vs. post consent. All too often, the job aids that sponsors or CROs provide sites (in industry funded trials) merely replicate the order from the protocol. If sites don’t segment these they can spend a lot of time, effort and resources working through a full laundry list of criteria rather than quickly and efficiently determining which criteria would quickly rule a prospective subject out from consideration.
I recently undertook an evaluation of 25 protocols that I have been involved with over the last several years.2 I was interested in evaluating what percent of the criteria could be segmented into pre-screening vs. screening criteria. My analysis covered a range of therapeutic areas, indications and phases of investigational new drug trials. The following graph captures the high level summary of my findings:
In terms of overall criteria, my findings were consistent with that of the Tufts Center for the Study of Drug Development (CSDD) 2012. In their report they identified a typical protocol has 35 inclusions/exclusion criteria and my analysis showed an average of 33 criteria. I should note, however, that many protocols have sub-criteria, which must be evaluated separately. This can lead to eligibility requirements in excess of 75 criteria in some cases. For purposes of this analysis I counted the total number based on how this was documented in the protocol, with sub-criteria only counted as part of the main criteria, hence the average of 33 eligibility criteria noted across the 25 protocols.
Of the entire criteria, my analysis suggests that on average about 2/3rds or 63% of the criteria can be determined at pre-screening. For protocols that involve identification of subjects within the site’s “known pool” of patients this presents a great opportunity for efficient pre-screening and enrollment optimization. While this in and of itself is interesting data, this is really only the first level of segmentation that sites must undertake to achieve deviation-free and efficient enrollment.
- Getz, K., et al. Variability in Protocol Design Complexity by Phase and Therapeutic Area. Drug Information Journal 2011 45 (4); 413-420
- Harper, B. Analysis of Pre-screening and Screening criteria across 25 protocols; independent unpublished research, 2014.
Editor’s Note: This blog post was originally published on April 18, 2014.