Hugh Davies – Seeking fair consent

ICR Ethics & GCP Forum – Part 3 of 5

Hugh Davies, Research Ethics Advisor to the Health Research Authority, concluded the morning with a discussion on the ethical issues around determining the true consequences of research and seeking fair consent. He subtitled his talk “Risk, trust and misunderstanding” and touched upon an issue that is crucial to the relationship between the research community and the wider public: the misunderstanding of the value of clinical research to healthcare, and the impact that this has on the willingness of patients to take part in clinical trials.

Hugh started by quoting David Wooten, who said that “effective healthcare only began when doctors learned to count”. While professionals in the field can all point to scandals relating to poorly conducted research, Hugh contended that we need to understand the denominator, and the context within that research is conducted.

There is much that RECs can do to mitigate the risks around clinical research. Relating to misconduct, the REC should look into the calibre and probity of the researchers. It is also important to recognise and address conflicts of interest, with scrutiny of data “ownership” and access, particularly around research publication policy. There are also issues around funding arrangements and particularly the choice of outcome measures: choosing “easy enpoints” that may not actually be relevant to how the medicine would be used in clinical practice. Hugh highlighted the work of the James Lind Initiative in bringing physicians and the public together to discuss which endpoints are of value.

Conversely, Hugh explained, there is also a risk to the public from unresearched healthcare. The protection of research subjects needs to be balanced with the lack of effective treatment. Worse still, Hugh mentioned the CRASH study, which demonstrated that a widely-used (but never researched) intervention was actually harming patients.

Obviously, the risks for research subjects include receiving treatment already shown to be of no value and of denying treatment that has already been proven effective. However, there are also risks of poor science and useless results, and RECs should consider these points. Data confidentiality and “distress” around research procedures should also be considered.

Quantifying risk & fair consent

Hugh moved on to discuss the concept of “fair consent”, which requires that we provide the best, most accurate information we can, as distinct from “fully informed” (which is technically impossible). However, a patient who is given an unduly negative perception of the risks involved in a clinical trial is not being “fairly informed”, and the HRA is currently working on a guideline on this topic.

In a way, Hugh said, the problem stems from our “linguistic poverty” in discussing and understanding research, particularly when it covers qualitative research and epidemiology in addition to the (more familiar to this audience) phase I-IV research.

Hugh quoted a piece of research done by Jonathan Sheffield, CEO of the NIHR CRN, which discovered that, of over 57,000 clinical claims through the NHS Litigation Authority, only 6 of these related to clinical trials. Evidence from throughout the EU suggests that researchers paid €75m in insurance premiums while payments were only €200,000 for the same period.

However, laying to rest the widely-held belief that taking part in a clinical trial results in better care, a 2005 study by Vist et al showed that there is actually no net benefit, but also no net harm. Of course, the findings of well-designed clinical trials provide evidence (whether positive or negative) that is of great benefit to the wider community, in terms of better evidence-based healthcare.

The HRA is currently working to design template text for parts of a Patient Information Sheet, and Hugh gave examples of introductory text to give the correct context for the research. For a Phase I study, he included information about the number of patients harmed in early phase research as compared with the total number of patients involved. Conversely, for a Phase IV study, he presented text suggesting that there might be no personal value in taking part, but that the information gained would be worthwhile to society.

Speaking from the floor, a delegate highlighted the importance of the person conducting the informed consent discussion, relying on the individual’s judgement on how this information should be used for each patient.

new%�hi8$Ih�Iorm, both to support these changes and also to enable the REC and R&D applications to be integrated wherever possible. The current system involves many iterations of form-filling, based on the poorer quality of protocols when it was developed. The new system will involve fewer forms, with attention going into the education and the improvement of the quality of protocols in the first place! Janet also mentioned an attempt to introduce the concept of “Good research practice”, particularly for academic researchers whose studies are not “clinical” in nature, but who still need to conduct their research to the highest level of quality. Touching on the topic of transparency, Janet promoted the use of a study’s IRAS number as a unique identifier to be used in all discussions relating to the study.

Janet closed with a call for everyone involved in research to play their part in unblocking and improving the current system.

A delegate asked whether it was time to “professionalise” ethics committees; Janet responded that there are several areas (eg, patient information sheet) that could be addressed by professionals prior to more general review by an ethics committee.