Niacin lowers LDL cholesterol and raises HDL cholesterol. The THRIVE trial randomly assigned more than 25,000 patients with vascular disease to receive either extended-release niacin with laropiprant or matching placebo. 245 sites were located in the UK, Scandinavia and China. During a median follow-up of 3.9 years, participants randomly assigned to niacin had lower LDL cholesterol and higher HDL cholesterol compared to matching placebo in patients whose LDL cholesterol had been standardized through prior statin therapy.
Vist et al (2008) have attempted to answer this question by comparing people who participate in a randomised with their counterparts who did not take part in a particular trial. Whilst longitudinal follow-up of participants was possible for trial volunteers, such data was not readily available for people who did not participate.
The starting point to do a trial well is to identify an important question to address. So much better, if this question emerges from a meta-analysis of the existing evidence as was the case with the ATLAS trial. The Early Breast Cancer Trialists Collaborative Group identified a number of small trials comparing 10 years treatment with tamoxifen with 5 years, but these early trials were too small to reliably assess the effects of longer treatment.
Patient and the public involvement in research, known as PPI, is very topical at the moment. Getting PPI right is neither simple or something that can be done without careful thought. There are logical points in the evolution of a research project that lend themselves to active involvement of patients and the public – these are:
- Formulation of the research question – is the question relevant to the population? Will the result be applicable to the population studied?
- Prioritisation of the research – is this the most important question to address in the study population? Will people want to take part?
- Research design – is the study feasible as planned? Can a sufficient number of people be recruited?
- Research conduct – how are people recruited? Are the study materials promoting participation? Can the design be simplified?
- Research outcome – how can the results be rapidly translated into practice? How does this study matter?
No single PPI exercise can check all of these boxes, but instead, patients and the public need to be engaged at the different stages of the research process. Deciding on the research question along with prioritising it is something that needs to happen early on, while matters to do with the conduct of the research can wait until the question is already formulated.
Ethics committees play an active and vital role in PPI, particularly in the aspects related to research design and conduct, but this is often overlooked as being separate from active patient and public involvement. This is not the case as ethics committees are formulated to promote discussion and dialogue between expert researchers and the members of ethics committees who represent patients and the public. These interactions are some of the most productive discussions and take place within the context of the ethical review of the project. Of particular note, is the process of ethical review of the participant information sheet and consent, which forms the central part of the request to participate and, as such, these discussions at the ethics committee are some of the most productive.
One aspect of ICH-GCP that appears to be lacking is proper recognition of the need for patient and public involvement in research. As has been pointed out previously, ICH-GCP still refers to research “subjects” rather than the correct term of “research participant.” Active involvement of patients and the public both early on and throughout the research is not a guarantee of success, but at the very least, it puts the research in a context that people should wish to participate if given the opportunity. Ethics committees play a vital role in this process and this should not be overlooked.
ICH-GCP states that it is an ethical standard for the design and conduct of research, but close inspection of the guideline leads to the conclusion that it is concerned with the process of ethics, specifically, the process of ethical review rather than the core principles of ethics. This is a pity because the principles that underpin research ethics are essentially straightforward and easy to grasp. I will try to outline them here.