What should authorities establish as the job of ethics committees and review boards? Two answers are: review of proposals for consistency with the duly established and applicable code and review of proposals for ethical acceptability. The present paper argues that these two jobs come apart in principle and in practice. On grounds of practicality, publicity and separation of powers, it argues that the relevant authorities do better to establish code-consistency review and not ethics-consistency review. It also rebuts bad code and (...) independence arguments for the opposite view. It then argues that authorities at present variously specify both code-consistency and ethics-consistency jobs, but most are also unclear on this issue. The paper then argues that they should reform the job of review boards and ethics committees, by clearly establishing code-consistency review and disestablishing ethics-consistency review, and through related reform of the basic orientation, focus, name, and expertise profile of these bodies and their actions. (shrink)

The recent tragic and widely publicised death of Jesse Gelsinger in a gene therapy trial has many important lessons for those engaged in the ethical review of research. One of the most important lessons is that ethics committees can give too much weight to ensuring informed consent and not enough attention to minimising the harm associated with participation in research. The first responsibility of ethics committees should be to ensure that the expected harm associated with participation is reasonable. Jesse was (...) an 18-year-old man with a mild form of ornithine transcarbamylase (OTC) deficiency, a disorder of nitrogen metabolism. His form of the disease could be controlled by diet and drug treatment. On September 13 1999 a team of researchers lead by James Wilson at the University of Pennsylvania's Institute for Human Gene Therapy (IHGT) injected 3.8 X 1013 adenovirus vector particles containing a gene to correct the genetic defect. He was the eighteenth and final patient in the trial. The virus particles were injected directly into the liver. He received the largest number of virus particles in a gene therapy trial.1 Four days later he was dead from what was probably an immune reaction to the virus vector. This was the first death directly attributed to gene therapy. It resulted in worldwide publicity, an independent investigation, the Federal Drug Administration (FDA) suspending all trials at the IHGT, an FDA, and a senate subcommittee investigation. At a special public meeting at the National Institutes of Health (NIH) in December 1999, James Wilson, also the director of the IHGT, said they still did not understand fully what had gone wrong.2 Even though a massive dose had been used, only 1% of transferred genes reached the target cells. (None of the patients in the trial showed significant gene expression. Art …. (shrink)

Failures in research ethics review examinedThe recent tragic death of Ellen Roche1 provides valuable lessons for research ethics review. The reasons for the wrongful administration of hexamethonium stem from researchers failing to act in certain ways, not from deliberate malicious or negligent actions.FIRST FAILING AND FIRST LESSON: PUBLICATION BIASThe first major failing was the failure of researchers who conducted the 1978 San Francisco study of hexamethonium to report similar adverse reactions.The tendency of researchers to fail to publish disappointing results2 or (...) results which are unattractive to them or their sponsors' interests has been well documented.3 It is called publication bias. An important part of publication bias is the failure to report all relevant or potentially relevant results. As this case illustrates, researchers must report or make available all research results, even negative results, and all potentially relevant outcomes of that research. If researchers believe an adverse event is unrelated to the study, they should explain why they believe this rather than omitting the event from their report. Elimination of publication bias is essential to scientific progress, to the protection of participants in research and in maintaining public faith in the integrity of scientists and doctors. Ethics committees and journals should make it clear that all adverse events—related or unrelated—to a project must be acknowledged, evaluated and further details made available to other researchers or the public if requested.SECOND FAILING: FAILURE TO CONDUCT A SYSTEMATIC REVIEWBut there is a more important failing. The most disturbing feature of this case was that literature documenting the pulmonary toxicity of hexamethonium was available before the trial began.In the study protocol submitted to the ethics committee, the researcher cited four reports involving 20 patients given inhaled hexamethonium without adverse event. However, Johns Hopkins investigators found a number of reports between 1953 and 1962, …. (shrink)

Research on human beings has significantly increased in ethical and scientific complexity. Ethics review is at a fork in the road. Either we significantly increase the resources we provide to support institutional research ethics committees. Or we abandon the institutional base of human research ethics review and move to model of expert suprainstitutional ethics committees.