Jessica Huening

by Jessica Huening

Protocol Templates: The Kinetiq Perspective

On March 17, 2016, the National Institutes of Health (NIH) and U.S. Food and Drug Administration (FDA) Joint Leadership Council (JLC) announced development of a research protocol template for Phase 2 and 3 clinical trials[1] in an effort to make the clinical trials process more efficient. The template is designed to meet standards consistent with the International Conference on Harmonisation (ICH) Guidance for Good Clinical Practice.[2]

There are several expected benefits in implementing the protocol template, according to Peter Marks, Director of FDA’s Center for Biologics Evaluation and Research.[3] Paramount is the acceleration of protocol development, thereby saving time and money in the overall clinical trials process.[4] The JLC anticipates investigators will realize time savings upfront by better identifying what elements should be in the protocol and how to organize them [5]

Use of a template in clinical trials protocol development is not a novel idea. TransCelerate Biopharma Inc., for example, has made a common protocol template available for use.[6] The JLC-developed template conveys the substantive information necessary for a protocol, accompanied by instructional and example text that requires editing by the drafter based upon specific study details. It also references relevant regulations, guidance, policy, and good clinical practice guidelines useful in drafting protocols. Indeed, given that the standardized template is being developed by the agencies that largely regulate clinical trials, it will likely elucidate agencies’ expectations for drafters and be of particular use to inexperienced investigators as they navigate the often confusing protocol development process. [7]

Potential Issues

The wholesale implementation of a standardized document has the potential to help efficiency, but it could also do the opposite.

The protocol template will likely remain a blunt instrument, while honing and developing unique issues relevant to the particular facts of a clinical investigation will be left to individual investigators. This may consequently act to restrict the protocol development process or inadequately describe the study. This is especially true for those aspects of clinical trial protocols prone to vary widely between studies, such as safety monitoring, procedures related to enrollment of vulnerable populations, and special considerations for ethically nuanced research (e.g. placebo controlled trials). Consequently, a protocol that does not fully capture the design intent, or leads to inadequate design, could incur avoidable re-work and cost.

Further, while the protocol template provides a strong starting point for investigators, it less effectively outlines the outer limit of what drafters should include in the protocol. To optimize efficiency, a well-crafted protocol arguably not only strives to effectively communicate all necessary study information in compliance with applicable standards but also ensures irrelevant and excessive details are absent. Investigators otherwise risk setting themselves up for costly non-value added processes, needless protocol amendments, and/or worst case, inadvertent protocol non-compliance.

Building on a Strong Foundation

A recent article by researchers at the Tufts Center for the Study of Drug Development and their collaborators summarized findings, reporting considerable costs associated with implementing substantive protocol amendments for multiple clinical trials during a defined study period.[8] Interestingly, the majority of the amendments required during the study period were necessitated by completely avoidable issues (protocol design flaws, inconsistencies in protocol, errors in protocol, etc.), or somewhat avoidable issues (site feedback requiring protocol revisions, recruitment difficulties, changes in strategy, etc.).[9] Researchers identify being able to anticipate and reduce the number of avoidable protocol amendments as a key improvement opportunity to reduce clinical trial costs and improve efficiency. Anticipating avoidable obstacles during the protocol development process starts with identifying the appropriate elements in a protocol; but optimizing effectiveness requires foresight, reflection, and specificity well beyond what a standardized form can provide.

The protocol template is a strong foundation on which to build a Phase 2 or 3 clinical trial protocol. However, clinical trials are not one-size-fits-all. Optimizing efficiency in protocol development also requires careful attention to the defining details of a study in order to avoid redistributing inefficiency and cost down the line.



[1] See NIH-FDA Draft Clinical Trail Protocol Template: Stakeholder Feedback Needed! (, The protocol template is designed for use in projects requiring an Investigational New Drug (IND) or Investigational Device Exemption (IDE) applications.

[2] See Protocol Template: Instructional and Sample Text document, Clinical Trails Protocol Template Preface, pg. a (

[3] Id.

[4] Id.

[5] Id. See also cited reference, Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. ( Roughly 85 percent of the 26,000 investigators registering a New Drug Application (NDA) in 2007 had previously participated in only one clinical trial.

[6] See TransCelerate Biopharma Inc. website (

[7] Id. See also cited reference, Transforming Clinical Research in the United States: Challenges and Opportunities: Workshop Summary. ( Roughly 85 percent of the 26,000 investigators registering a New Drug Application (NDA) in 2007 had previously participated in only one clinical trial.

[8] Getz, K., Stergiopoulos, S., Short, M., Surgeon, L., Krauss, R., Pretorius, S., Desmond, J. & Dunn, D. (2016). The Impact of Protocol Amendments on Clinical Trial Performance and Cost. Therapeutic Innovation & Regulatory Science, I-6. doi: 10.1177/2168479016632271. The median direct cost of implementing a substantive global protocol amendment at 15 pharmaceutical companies and contract research organizations between 2010 and 2013 was found to be $141,000 for phase II trials and $535,000 for phase III trials. Note, unlike the investigators likely using the protocol template, these costs are associated with protocols supported by industry across many sites. Costs may be even higher per capita, however, given the difference in resources and experienced protocol review/vetting process of industry sponsored clinical trials.

[9] Id. at 4

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