This piece is again modified from a section written by me as a resource supporting the Edinburgh Surgical Sciences Qualification (ESSQ) MSc Masters in Surgical Sciences. It is not meant to be an exhaustive guide more an outline. Similar regulatory processes exist in most countries but I have only included links for the UK. Finally as always opinions are my own.
It is a principal, which has broad international agreement, that clinical medical research should be subject to regulation. This regulation is primarily to protect human subjects from harm but also to ensure standards of research, probity and recording are maintained.
Most countries in the world are signatories to agreements based on the Declaration of Helsinki 1964 which set out a modern set of standards and principles for the humane and ethical conduct of clinical medical research. These ethical principles were laid out partly in response to atrocities involving human experimentation perpetrated during the second World War (declaration of Geneva 1948). The Declaration of Geneva sets out what is essentially a modern Hippocratic Oath describing the standards of care and behaviour by which modern doctors are expected to conduct themselves. The Declaration of Helsinki sets out principles designed to guide ethical medical research. To perform experiments on human subjects or even to perform experiments on tissues or samples derived from human subjects it is necessary to obtain permission from a regional ethical committee. Such committees are composed of medical and lay members who study applications and ensure the safety, security and rights of patients are not contravened by participation in the research.
Risk, harm and objectivity.
There are so many potential problems in conducting clinical research but research is essential because it is such an integral and important component of medical progress. Balancing levels of risk and harm is something that doctors do on an almost daily basis but when it comes to medical research we need to have objectivity and it is not enough for the medical profession to decide what kinds of research are OK and which are not, – this must be a societal decision. This is the reason that lay people are so important on ethics panels (IRB’s), why research subjects must have fully informed consent and why research should be published in the public domain. Even with good planning there is still an element of risk to research. If you dont believe that well planned, thought out, regulated and resourced research can go wrong you should read this.
- New drugs are often trialled in human subjects and this requires permission from the Medicines Healthcare products Regulatory Authority (MHRA) and in some cases may also require the issue of a clinical trial certificate or clinical trial authorisation. The framework for governance for clinical trials for the MHRA and European Medicines Agency are by design very similar. Both the MHRA and EMA websites are full of helpful information on routes to trials and obtaining regulatory approval for drugs in development. This BBC link is interesting and discusses how drugs are approved in the context of the Northwick Park drug trial disaster. Surgery research is interesting because new procedures unless they involve new technology are not necessarily subject to the same constraints as drugs. This does not mean that they are not subject to regulation and surgical trials do require the same ethics committee/IRB scrutiny as any other clinical research trial.
- Any clinical trial which uses organisms or DNA or other genetic material that have been genetically modifies as vectors or treatment needs to be passed by the Gene Therapy Advisory Committee. This Government body was set up to review the safety of human treatments involving genetically modified organisms or genetic material as therapy and its functions have now been taken over by the National Research Ethics Service. This committee also assesses some stem cell therapy trials where genetic modification of cells has been performed.
- The Human Fertilisation and Embrology Authority is the Government appointed body responsible for licensing clinical practice and research associated with the use of human gametes and also human embryos. Some stem cell research is also subject to regulation by HFEA
In the past it was necessary to submit multiple copies of ethics applications and research protocols to each of the agencies involved in different aspects of approval or licensing of a research study. The Integrated Research Application System (IRAS) is a relatively new system where a single online application form can be completed and is then automatically populated and split to create applications to all of the relevant agencies for example ethics, ARSAC, GTAC and R&D approval. It is hoped that this system will shorten the time needed to complete approval for studies and avoid duplication of information provision.
- If a research trial requires that patients be exposed to ionising radiation that they would not normally be exposed to in the course of their treatment then a licence is required from the Administration of Radioactive Substances Advisory Committee (ARSAC). This may relate to administration of a radioactive substance but might also be because of additional exposure to x-rays through for example multiple CT scans.
- All research conducted in the NHS, using NHS patients, or NHS facilities or involving time of NHS staff must be approved by the local Research and Development Committee (R&D). The purpose of this is is to ensure that adequate funding is provided to cover NHS costs associated with research, to protect the health and safety of patients and NHS staff, and to protect the intellectual property interests of the NHS in the research.
Part 2 of this blog will follow soon covering activities and responsibilities of ethics committees IRB’s and research probity.
© 2012 SJ Wigmore