Protocol is a document that describes the background, objectives, rationale, design, methodology (including the methods for dealing with AEs, withdrawals etc.) and statistical considerations of the study. It also describes the conditions under which the study shall be performed and managed. The content and format of the protocol should take into consideration the adopted Standard Operating Procedures (SOPs), the regulatory requirements and the guiding principles of Good Clinical Practice. The term protocol, unless otherwise specified, relates to the latest version of the document, read in conjunction with all its appendices and enclosures.
A well-designed study relies predominantly on a robust and complete protocol. Therefore, it is advisable that the protocol is developed with contributions from a multi-disciplinary team (therapeutic experts, clinicians, operational experts, Investigational Product experts, biostatisticians, medical monitoring experts, etc.)
Resources for protocol development
Provided below are standard templates that can be used by researchers to develop and design their study protocol:
- Table 2 of the Third Schedule (page 213) in the New Drugs and Clinical Trial Rules, 2019 outlines the essential components of a proposed protocol. This template can be used to develop a protocol as per the information provided.
- Checklist and format, to guide preparation of a protocol, adapted from the National Ethical Guidelines for Biomedical and Health Research involving Human Participants. This document may be used as a template to prepare a protocol.
- ICMR and CDSCO have provided a Study Protocol Guidance in the Handbook for Applicants and Reviewers of Clinical Trials of New Drugs in India. This template may be used to prepare a protocol as per the guidance available in this handbook.
- The SPIRIT website provides comprehensive resources for protocol writing (figure, checklist and paper).
- CReDO Template – developed during a workshop conducted by Tata Memorial Centre and National Cancer Grid of India (https://tmc.gov.in/credo/).
- The NIH (National Institutes of Health) has developed an online tool for protocol writing and a guidance document. Both the document and the online tool should be used in consideration with the Indian regulatory requirements.
- The WHO also has a suggestive template that can be used.
- The National Institute for Health Research has two templates available.
Additional points to be considered during protocol development
- The protocol (and other essential documents) must be a version controlled document, i.e. dated and numbered.
- From the point of view of quality, it is essential that the Protocol discusses the Quality Management plan (Quality Assurance and Quality Control measures) of the trial.
- The protocol must elaborate on processes that will be carried out during the trial to ensure data credibility, and which personnel will have access to the source data / raw data.
- This document by the Clinical Trials Transformation Initiative (CTTI) discusses questions to consider for each Clinical Trial Quality Factor, at the time of trial design and protocol development. These factors are critical to data integrity and reliability, and protection of research participants.
Resources for Sample Size Calculation
- OpenEpi is a free, open source software that can be used for calculating the sample size in epidemiological studies. The website also provides links to many internet-based calculators.
- nMaster 2.0 is a software developed by the Department of Biostatistics, CMC Vellore for sample size calculation. This is however not a free software and one can contact the nMaster team for conditions of its use.
Role of Patient Public Involvement (PPI) during protocol development (community engagement)
Involvement of the community or the public can enhance the way research is conducted, communicated and interpreted. Representatives from the community can be instrumental in ensuring better public engagement, thereby enabling a conducive environment for research. Unlike other countries, patient public involvement is not mandatory in the research process in India. However, it is recommended that the researcher considers the contribution from the community before, during and after the research, to mitigate culturally sensitive issues, and ensure that the health requirements of the community are being addressed. The researcher may decide the degree of their engagement considering the type of research being carried out.
An example of engaging the community during the trial is by forming a Community Advisory Board or Group (CAB or CAG). This group can act as an interface between the community, the researcher and the ethics committee. It is important to highlight that; CAB or CAG does not replace individual informed consent.
Further reading for PPI
- Sahay, S., & Mehendale, S. (2011). Engaging community to support HIV prevention research. Eastern journal of medicine: EJM, 16(2), 168-177, link to the article.
- Sahay, S., Kumar, M., Srikrishnan, A. K., Ramanathan, V., & Mehendale, S. (2013). Experiences in recruiting volunteers through community based initiatives in phase-1 vaccine trials in India. Human vaccines & immunotherapeutics, 10(2), 485-91, link to the article.
- New Drugs and Clinical Trial Rules, 2019, G.S.R. 227(E), Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, available online (last accessed on 03.04.2019).
- Good Clinical Practices for Clinical Research in India, Central Drugs Standard Control Organization, Ministry of Health and Family Welfare, 2001, available online (last accessed on 26.02.2019).
- National Ethical Guidelines for Biomedical and Health Research involving Human Participants, Indian Council of Medical Research, 2017, available online (last accessed on 26.02.2019).