03 · What You Need to Know
The Literature Is Part of the Protocol's Scientific Foundation
The Protocol Should Explain Why the Research Is Needed
A protocol should not begin from the assumption that a plausible research question automatically justifies a new study. Existing knowledge has to be considered.
For example, the World Health Organization's recommended research protocol format describes the rationale as explaining why the research needs to be done in light of current knowledge and calls for a description of the most relevant published studies. WHO also treats the methodology as a central part of the protocol, including the procedures, measurements, and other operational details of the proposed research.
Requirements vary among disciplines, institutions, sponsors, registries, ethics bodies, and study types, so this should not be interpreted as a universal protocol template. It illustrates the underlying connection: a defensible rationale and a defensible method both depend on understanding relevant previous evidence.
Search Before the Major Design Decisions Become Fixed
The literature may reveal that an outcome measure is poorly suited to the target population, that a particular follow-up interval misses important effects, that an intervention has known implementation problems, or that previous studies repeatedly encountered attrition or bias.
Those findings matter most while the protocol can still change. The search conducted before designing a new study should therefore feed directly into protocol development rather than becoming a retrospective exercise used only to decorate the rationale with references.
Search for Existing Evidence Syntheses Early
Relevant systematic reviews, meta-analyses, scoping reviews, guidelines, and other high-quality syntheses can provide an efficient overview of what is known and uncertain. They can also identify important primary studies and terminology.
Check their scope and search dates. A review may exclude your population, intervention, setting, outcome, methodology, or other element of interest. New research may also have appeared since the review's final search.
Investigate the Methods Used in Previous Studies
A protocol search should include literature capable of informing the methods, not only papers supporting the study's substantive hypothesis.
Depending on the research question, this may include evidence about measurement properties, instrument validation, intervention procedures, sampling, recruitment, expected event rates, attrition, comparison conditions, data collection, statistical methods, implementation, and feasibility.
The relevant literature will differ substantially across research designs. A qualitative interview study, laboratory experiment, educational intervention, epidemiological survey, and randomized clinical trial do not require identical types of methodological evidence.
Ethical Justification and Scientific Justification Can Be Connected
For research involving humans, scientific weakness can have ethical consequences. Participants should not be exposed to burdens or risks for a study whose question is poorly justified or whose design cannot adequately answer it.
WHO emphasizes protection of the dignity, rights, and welfare of human research participants and states that research involving human beings should undergo ethics review. The exact ethical and regulatory framework applicable to a study depends on jurisdiction, institution, sponsor, and study type.
A literature search can contribute to ethical planning by identifying known risks, adverse effects, participant burdens, effective alternatives, previous recruitment difficulties, or evidence that alters the expected balance between potential benefits and harms. Literature searching does not replace formal ethics review, but it can materially inform the protocol submitted for that review.
Watch Out
Do not treat the literature review as an administrative section completed after the protocol has already been designed. If existing evidence could reasonably change participant protections, measurements, procedures, or the justification for conducting the study, it belongs upstream in protocol development.
Search Thoroughness Should Reflect the Consequences of Missing Evidence
Not every protocol requires the same search effort. Consider what would happen if an important study were missed.
If the consequences are minor and the project is exploratory, a focused search may be adequate. If overlooked evidence could reveal a known safety issue, show that the proposed question has already been answered, invalidate a key measurement choice, or expose participants to unnecessary procedures, considerably stronger searching is warranted.
This proportional approach avoids two extremes: treating every protocol as if it required a systematic review, and treating a few convenient citations as sufficient for every study.
Claims About Research Gaps Need Their Own Evidential Support
Protocols often justify a study by stating that previous research is limited, inconsistent, methodologically weak, or absent. Those statements are empirical claims about the literature.
If the protocol's necessity depends heavily on such a claim, the search should be capable of testing it. Before asserting a gap, consider how thoroughly you need to search before concluding that the relevant uncertainty remains.
An absolute claim that no previous study exists carries an even higher burden. Failure to retrieve a study is not by itself evidence that none exists.
A Protocol Search Is Not Automatically a Systematic Review Search
A conventional research protocol can be based on a rigorous, documented literature search without meeting the methodological requirements of systematic evidence synthesis. The purpose is different: the search supports the rationale and design of the planned study.
If the protocol itself describes a systematic review, however, literature retrieval becomes part of the research method. In that situation, the systematic review search should be designed and reported according to the relevant methodological and reporting standards.
Search supporting a research protocol
Provides sufficient evidence to justify and design the planned study.
Search specified by a review protocol
Forms part of the methodology used to identify evidence for the review itself and may require detailed reproducibility.
Document the Search Well Enough to Update It
Keep records of important databases, platforms, search terms, dates, limits, and supplementary searching. Even if these details never appear in the final protocol, they make the evidence base easier to check and update.
Documentation becomes especially important when the protocol makes strong claims about evidence coverage or when another researcher, reviewer, sponsor, or ethics committee needs to understand how the literature supporting a decision was identified.
Update the Evidence When Protocol Development Takes Time
A protocol can take months to develop, obtain approvals, register, or fund. Relevant evidence can appear during that period.
Before the protocol becomes operational, consider updating searches central to the rationale, safety, and major design assumptions. Whether an amendment is required after formal approval depends on the nature of the new evidence and the applicable institutional, regulatory, or sponsor procedures.
07 · A Quick Checklist
Before Finalizing a Research Protocol, Check the Evidence Base
Before the protocol is finalized, check:
I can explain why the proposed research is needed in light of current relevant knowledge.
I checked relevant recent reviews and important primary studies rather than relying on a few convenient citations.
My databases and search terminology are appropriate to the disciplines and concepts represented by the study.
Previous research has informed important methodological choices such as measurements, procedures, sampling, comparison conditions, or analysis where relevant.
For research involving participants, I searched relevant evidence about foreseeable risks, burdens, benefits, and practical problems where these could affect the protocol.
Claims about research gaps or absent evidence are no stronger than the search supporting them.
I retained enough information about important searches to update or explain them later.
I checked the current requirements of the relevant institution, sponsor, ethics body, registry, reporting guideline, or regulatory authority rather than assuming one universal protocol standard.
