Medical Research Regulation and Risk Management: An Analysis of Issues in Human Protection Following the March 2006 London Incident

By Grégoire Moutel, Medical Ethics and Forensic Medicine Laboratory, Faculty of Medicine Paris 5 and Sffem, French and Francophone Society for Medical Ethics

Protecting participants is a crucial aspect of medical research, as it inherently involves risks.

Several core, interdependent themes form the basis of biomedical research ethics:

Respect for research subjects, notably through informed consent.

Researchers' responsibilities toward participants.

Minimizing any unnecessary suffering or harm.

Rejecting any risk of injury, disability, or death beforehand.

Ensuring that participants are only involved if the research follows a rigorous scientific framework.

Allowing participants the freedom to withdraw from the study if they feel they have reached a mental or physical limit.

In 1947, these principles were established by the international community, yet in 1966, Dr. Henry Beecher, Harvard's anesthesiology research chair, published an article in the New England Journal of Medicine listing 22 U.S.-based studies that ignored these ethical principles. Beecher highlighted instances of:

Injecting living cancer cells into institutionalized elderly individuals to analyze immune resistance.

Withholding penicillin from syphilitic patients in a control group for a long-term syphilis study.

Injecting the hepatitis B virus into young residents at a New York psychiatric institution.

Inserting a catheter into the bladder of 26 newborns for a series of x-rays to study bladder function.

The medical and scientific communities have thus strongly emphasized the principles adopted by democratic states in Helsinki. While acknowledging the role of medicine in advancing medical knowledge, they stress the following:

While risk is recognized, research must prioritize participants' health over scientific or societal interests.

Scientific validity must be ensured through prerequisites, such as reviewing laboratory and animal research, writing a valid experimental protocol, and involving competent, responsible scientists.

An independent committee must review the protocol, free from conflicts of interest with sponsors or researchers.

In all situations, the physician must protect the participant's life, health, dignity, privacy, and physical and mental well-being.

The benefit-risk ratio must be assessed and deemed acceptable by the committee, though research involving healthy volunteers or patients is permitted if the study’s objective is of sufficient medical and human importance to outweigh risks.

Research conducted as part of treatment should offer diagnostic, therapeutic, or preventive benefits, especially when existing methods are insufficiently effective. This innovation must meet ethical research standards and compare the new treatment to the standard one.

Information given must be appropriate, clear, understandable, and complete regarding objectives, risks, and constraints, and physicians must ensure comprehension.

Physicians must distinguish between care and research when discussing treatment and maintain the doctor-patient relationship, regardless of the patient’s participation.

Written consent must be freely obtained without coercion. If the protocol involves individuals unable to consent legally, the population selection must be justified, provide a benefit, and obtain both committee approval and the legal representative's consent.

London Incident of March 2006

In March 2006, a clinical trial was conducted at Northwick Park Hospital, London, involving the antibody TGN 1412, potentially useful for cancer, infectious, or immune disorders, including multiple sclerosis. Six out of eight volunteers experienced severe symptoms, including intense pain, vomiting, unconsciousness, and required intensive care. Only the placebo group remained unaffected.

This event, widely reported, reminded the public that biomedical research always involves risks. Some media referred to participants as "human guinea pigs," suggesting the trials involved sick patients instead of healthy volunteers. This raised questions and highlighted two needs: to clarify what medical research entails, including its inherent risks, and to strictly adhere to ethical and procedural standards in clinical trials, which protect participants.