Howard Mann, M.D.

Program Associate, Division of Medical Ethics, University of Utah School of Medicine, Salt Lake City, Utah.


The ASSERT statement represents a declaration and elaboration of the necessary requirements for the ethical conduct of human subjects research in the form of randomized controlled clinical trials. It serves both as an explication of scientific and ethical precepts constitutive of the proper conduct of clinical research and, in particular, a proposal intended to operationalize these precepts in the context of review of proposals for trials by research ethics committees. The latter aspect is effected through the formulation of a checklist of items to be addressed in formal applications for research, and systematically evaluated by research ethics committees.

The checklist encompassed within the table below contains informational items pertinent to each of the five sections to be addressed in the Application for Research. Hyperlinked items in the description sections will direct the reader to separate pages wherein elaboration is provided. Some of the hyperlinks will take the reader to pages on the CONSORT Web site, where specific examples and elaboration will be found. Each linked page will open in a new browser window -- close this window to return to the checklist.

Checklist of sections and items to include in an application for research

Exposition of scientific background, rationale and relevance. This should be referenced to a Systematic Review whenever feasible.
Trial registration
Details about trial registration and International Standard Randomised Controlled Trial Number (ISRCTN)
Public dissemination of trial results
Plans for public dissemination of results; name/s and affiliation of individuals responsible for results dissemination, including contact information.
(items 4-12 are from the CONSORT statement)
Eligibility criteria for participants.
Specific objectives and hypotheses
Clearly defined primary and secondary outcome measures and, when applicable, methods used to enhance the quality of measurements
Sample size
How sample size was determined
Randomization -- Sequence generation
Method used to generate the random allocation sequence, including details of any restriction (e.g., blocking, stratification).
Randomization -- Allocation concealment
Method used to implement the random allocation sequence (e.g., numbered containers or central telephone), clarifying whether the sequence was concealed until interventions were assigned.
Randomization -- Implementation
Who generated the allocation sequence, who enrolled participants, and who assigned participants to their groups.
Blinding (masking)
Whether or not participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment. When relevant, how the success of blinding was evaluated.
Statistical methods
Statistical methods used to compare groups for primary outcome(s); Methods for additional analyses, such as subgroup analyses and adjusted analyses.
Recruitment of participants
Description of the populations from which participants will be recruited, including details concerning location, age groups, gender, ethnicity and whether participants will be recruited from vulnerable groups.
Interventions offering the prospect of health-related benefit
Ordered enumeration and explication of research interventions offering the prospect of direct health-related benefits
Interventions performed solely to answer the research question
Ordered enumeration and justification of interventions (invasive; measurement; data collection; surveys, etc.) performed solely to answer the research question and generate generalizable knowledge.
Clinical equipoise
Description and justification of control and experimental arms, including modes and dosages of drug administration. Reference the claim of clinical equipoise to an applicable Systematic Review whenever pertinent.
Trial monitoring plan
Description and justification of a formal trial monitoring (safety and efficacy) plan. Details concerning a DSMB (if applicable), including names/affiliations of members and details concerning the stopping guidelines for the trial, and how they were chosen.
Communication of protocol changes and trial monitoring results
Details concerning the method and timing of transmission of protocol changes and trial monitoring results to research ethics committees.

Research Ethics Committees should incorporate this checklist in their Applications for Research, and reference this Web site in the application to assist investigators in complying with ASSERT's requirements.


Applicants for research approval should use this checklist to ensure that all the associated items are addressed in the Application for Research. Commercial sponsors of drug trials typically provide investigators with an Investigators Brochure in compliance with Good Clinical Practice (1), the latter formulated by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (2), for use in drug trials. While the brochure may address certain aspects of the checklist items in a limited fashion, it is not a substitute. The checklist items may be considered constitutive of a Protocol Summary for distribution to members of the research ethics committee evaluating the trial application.

In multicenter trials, local research ethics committees are unable to influence the design of a trial submitted for review by local investigators, the latter having been recruited to participate by the trial's Steering Committee or a contracted third party . The committee may request amendments or changes to the submitted Informed Consent document, but actual approval is reduced to a take-it-or-leave-it proposition. By endorsing the ASSERT statement, and considering only applications that are in conformity with its itemized requirements, committees will help assure the ethical conduct of research.

Research ethics committees have been criticized for not paying sufficient attention to the relevance of the research they approve; ensuring that clinical equipoise is present at trial inception; and ensuring the public dissemination of the results of the trials they approve (3). By endorsing the ASSERT statement and conducting continuing review of the research until the trial's results are reported, committees will be positioned to respond to such concerns.

Funding agencies may also stipulate provision of pertinent checklist items in applications for research funding. Such agencies have an obvious interest in ensuring the responsible use of limited financial resources. In particular, the requirement for scientific and social value is relevant to such agencies.

Because the checklist represents a structured approach to the ethical conduct of research, it may also be used as an evidence-based research tool to determine whether compliance with the ASSERT statement results in improvements in the conduct and reporting of trials. Authors of manuscripts submitted for publication should be encouraged to report whether the trial was approved by a research ethics committee, and whether it was conducted in conformity with the ASSERT statement. This will enable researchers to determine whether this leads to a verifiable improvement in associated parameters such as the assurance of clinical equipoise at trial inception; the publication of trial results, whether positive or negative; and the reporting of results in conformity with the CONSORT statement.


References available online are hyperlinked.

1. Good Clinical Practice. International Conference on Harmonization. Investigator's Brochure.

2. International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.

3. Savulescu J, Chalmers I, Blunt J. Are research ethics committees behaving unethically? Some suggestions for improving performance and accountability. BMJ 1996; 313:1390-1393.