Dr. Nimita Limaye returns to continue answering our guest audience questions in regards to authoring a clinical study protocol! This week, she explains the importance of protocol synopsis and ensuring the completeness of the protocol, as well as defines crowdsourcing and its role in writing a clinical study protocol.

If you missed the first part of the series, you may read it here.

Jane: During our last discussion, you had referred to a protocol synopsis. What are some of the important questions we should be asking to author a synopsis?

Dr. Limaye: A clinical trial protocol is the roadmap to the success of the clinical trial. Some of the fundamental questions that one should be asking include defining the research question, specifying the number of the subjects and the inclusion / exclusion criteria, understanding the study rationale and study design, and identifying the primary and the secondary study objectives. It is essential that clear cut measurable end points for these objectives are identified. Some may be ‘hard’ or ‘objective’ end points, while others may be ‘soft’ or ‘subjective’ end points. Not only should the end points be clearly defined, but the writer needs to ensure that these are clearly linked to the objectives. If the objectives or the end points are not outlined succinctly in the protocol by the medical writer, this can result in the failure of the trial. Another important aspect includes the regulatory authority to which the data will be submitted, since the study should be conducted in a manner that complies with the relevant clinical trial and data security and privacy regulations and the writer needs to be able to ensure that due weightage is given to the same. While the writer will receive data and inputs from multiple stakeholders, based on which he / she will author an article, it is important to remember that an experienced writer is also a valuable stakeholder and contributor to the development of a robust clinical trial protocol, and not just a data aggregator.

Jane: How can a writer ensure the completeness of a clinical trial protocol?

Dr. Limaye: The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 Statement outlines a 33-item checklist of minimum recommended protocol items that should be present in a protocol. A protocol that is drafted using this checklist is more likely to be complete and would potentially facilitate faster review, as it would avoid unnecessary queries resulting from missing or unclear protocol information. In fact, SPIRIT-AI is being developed, which will specifically focus on clinical trials in which the intervention includes an ML or other AI component. While SPIRIT focuses upon the essential elements of a protocol, CONSORT defines the Consolidated Standards of Reporting Trials, and CONSORT also has a CONSORT-AI extension, like SPIRIT-AI.

Jane: What does one mean by the ‘crowdsourcing’ of clinical trial protocols’?

Dr. Limaye: Jane, a clinical study protocol outlines the rationale, the study design, and the implementation strategy of the clinical trial. But tell me, for whom are clinical trials conducted?

Jane: For the patients of course. What are you getting at?

Dr. Limaye: If trials are being conducted for patients, don’t you think that they should be the ones providing inputs to that protocol, considering that they are the ones that are going to be impacted? ‘Crowdsourcing’ is an approach wherein creative inputs from a network of patients and physicians are sought via an online portal. The expectation is that this would improve accrual and help derive more meaningful endpoints. Various platforms such as ‘Smart Patients’ and others are available. Another interesting example is Transparency Protocol Crowdsourcing (TPC). This platform leverages NLP and analyzes inputs to help sponsors design more ‘patient-centric’ protocols’.