Declaration of Helsinki

The Declaration specifically addresses 'medical research involving human subjects,' so strict application is to biomedical/clinical research. However, its principles (ethical review, informed consent, risk-benefit assessment) are adapted by most research ethics committees to all human subjects research. Check your institution's IRB/REC scope: many mandate Declaration compliance for research in ANY discipline if it involves human subjects. Even if your IRB does not, adoption of Declaration principles is good practice and required for publication in major journals covering your field.

THERAPEUTIC RESEARCH: Offers potential direct benefit to enrolled subjects; includes clinical trials of new treatments, some comparative effectiveness studies. Helsinki permits higher risk-to-benefit ratios because subjects may benefit directly. Example: enrolling HIV+ patients in trial of experimental antiretroviral drug. NON-THERAPEUTIC RESEARCH: Generates knowledge for future patients but offers no direct benefit to current subjects. Includes phase I drug studies (testing safety/dosage in healthy volunteers), mechanistic studies, epidemiology. Helsinki requires stricter risk assessment for non-therapeutic research—risks must be minimized and justified by research importance. Important: many studies are mixed (e.g., a trial offering new treatment to some subjects while comparing to standard care for others). Declare therapeutic vs. non-therapeutic components clearly; apply appropriate ethical standards to each.

Follow the more protective standard. If your national regulations (e.g., local IRB rules) are less stringent than Declaration, and you aim to publish in major medical journals (JAMA, Lancet, BMJ, NEJM), journals will require Declaration compliance before acceptance. If national regulations exceed Declaration (e.g., mandatory monitoring for all research vs. Declaration's 'significant risk' standard), follow national law. When misalignment creates conflict, communicate with your IRB and target journal: some journals may grant exceptions for research meeting high ethical standards even if not identical to Declaration wording, but do not assume—ask before submission.

Declaration states: if research identifies beneficial intervention not yet standard care, researcher must provide post-trial access. 'Reasonable' is interpreted by ethics committees and journal editors; it varies by context. EXAMPLES: (1) Continuing investigational drug for subjects who benefit until approved for commercial sale or incorporated into standard care. (2) Facilitating patient access through government health system or non-profit organization. (3) Providing intervention free-of-charge or at cost to subject population. (4) For research in low-resource countries, committing to make intervention available locally post-trial. What is reasonable depends on feasibility, cost, and benefit magnitude. Submit your post-trial plan to REC/IRB for review; they will advise if plan is deemed reasonable. Avoid vague commitments ('we will work to provide access'); be specific about funding source, mechanism, and timeline.

This is contentious in Declaration interpretation. The principle: if effective standard treatment exists, withholding it via placebo control is unethical UNLESS (1) true state-of-the-art uncertainty exists (expert disagreement on best treatment), (2) the new treatment offers substantial promised advantage, or (3) the study investigates how to deliver standard treatment most effectively (implementation research). Example: placebo-controlled COPD trial when standard inhalers exist—generally unethical. Acceptable: trial of new antibiotic vs. standard antibiotic when both are effective, investigating improved side-effect profile. Researchers and ethics committees should clearly justify any placebo use in setting of effective alternative. Major journals scrutinize placebo-controlled research; Declaration wording has been revised multiple times to address this concern. If your study requires placebo control, justify clearly to ethics committee and expect rigorous review.