Informed consent and ethics review in clinical trials

Clinical trials test whether new medicines are safe and effective in people, but they do so by exposing participants to uncertain risks in the hope of generating useful knowledge. To keep that balance from tipping against the participant, modern research relies on two safeguards: informed consent and independent ethics review. Neither is a formality — together they form the backbone of research ethics and are required by regulators worldwide before a trial can begin.

The Declaration of Helsinki and the ethical framework

The principles commonly cited today were codified in the Declaration of Helsinki, adopted by the World Medical Association in 1964 and revised several times since. It states that the well-being of the individual participant takes precedence over all scientific and societal interests, and that research must be justified by its potential importance relative to the risks involved. The Declaration builds on older ideas — respect for persons, the duty to minimise harm, and fairness in selecting participants — that developed in response to historical abuses. Although the Declaration is not itself a law, its principles have been incorporated into national regulations, institutional policies, and the good clinical practice standards used by regulators such as SAHPRA, the FDA, and the EMA.

Ethics committees and their role

Before any participant is enrolled, a trial protocol must be reviewed and approved by an independent ethics committee — also called an institutional review board or research ethics committee. These committees bring together scientists, clinicians, and non-scientist members such as ethicists, lawyers, or community representatives. They assess whether the research question is important enough to justify exposing people to risk, whether the design can actually answer it, and whether risks have been minimised. They also look at how participants will be recruited, whether incentives are undue, and whether vulnerable groups — children, prisoners, people unable to consent for themselves — are being appropriately protected.

In many countries a single committee review is sufficient; in others, especially multi-centre studies, several committees may be involved alongside the national medicines regulator. In South Africa, SAHPRA registers clinical trials and works with research ethics committees registered with the National Health Research Ethics Council. A trial must hold both ethics approval and regulatory authorisation before the first participant is enrolled, and material changes to the protocol generally require re-review.

Informed consent

Informed consent is the process by which a person voluntarily agrees to take part in research after being told what it involves. It is more than a signature — it is an ongoing conversation. The consent discussion and documents should explain the study's purpose, what participants will be asked to do, foreseeable risks and discomforts, potential benefits, alternatives to participation, and how personal data and biological samples will be stored or shared. Participants must be told they can withdraw at any time without penalty or loss of access to their normal care.

Consent must be given freely, without coercion or excessive inducement. Where participants cannot consent for themselves — young children, or adults with impaired decision-making — a legally authorised representative may provide consent, and the participant's own assent or objection is generally sought where possible. Consent materials should be in plain language and, where appropriate, translated into the participant's preferred language.

Ongoing oversight and protections for vulnerable participants

Ethics review does not end at approval. Committees require periodic progress reports, notification of serious adverse events, and re-review of any protocol changes. If unexpected harms emerge or the balance of risk and benefit shifts, a committee can suspend or stop the study. Many large trials also appoint an independent data safety monitoring board that reviews unblinded safety data at intervals and can recommend early termination if a clear harm or benefit emerges.

Additional protections apply to specific situations. Pregnant women are generally excluded from early-phase trials and only enrolled in later phases when potential benefit justifies risk. Trials in children require age-appropriate consent and assent procedures. Research in resource-limited settings faces particular scrutiny over whether it responds to local health needs and whether participants will continue to have access to any effective intervention after the trial ends — questions emphasised in successive revisions of the Declaration of Helsinki.