Clinical trials: background information
The World Health Organization (WHO) defines a clinical trial as any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes [1]. Interventions may include, but are not restricted to drugs, cells and other biological products, surgical procedures, radiologic procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc. [2].
Clinical trials test the safety and efficacy of medical treatments, providing the body of scientific evidence on which the pharmaceutical industry is built. Human medicines cannot be sold without permission from a licensing authority and permission will not usually be granted unless a clinical trial has demonstrated the medicine’s success in treating the condition for which it will be marketed [3]. Clinical trials, in addition to generating valuable scientific evidence, also provide patients with an important way of accessing products that have not yet reached the market, offering hope to those for whom existing treatments have failed. The necessity for a clinical trial to be performed before a medicine can gain regulatory approval means that trials are also big business [4].
Medical research in mental disorder is needed to answer questions that are important to people affected by mental health problems, their families and friends, and the people working to support them across the health and social care sector and beyond [5]. Mental ill-health impacts on all aspects of peoples’ lives and medical research can make a tremendous positive impact on those who suffer from mental disorders through the development of new and better medicines and therapeutic techniques and technology [5]. This in turn can benefit the whole of our society by generating social and economic benefits that contribute to thriving communities. Research provides hope that those in future generations experiencing mental health problems will have a better quality of life and place in society [5].
According to the Mental Health Foundation:
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Mental health problems account for a quarter of all ill health in the UK yet they get less than 6 % of all health research funding.
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1 in 10 young people are affected by mental health issues.
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Currently 75 % of those with a mental health problem receive no treatment or support.
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Suicide is the most common cause of death in young men.
The social and economic cost of mental health problems in England alone is £105 billion and UK businesses lose £26 billion a year due to mental health problems in the workforce [6].
Current psychiatric treatments are only partially adequate and certain psychopharmacological modalities carry unpleasant or even severe side-effects such as sedative adverse reactions and immunological dysfunction [7]. As in any branch of medicine, participation in clinical research studies or trials might provide a patient with the opportunity to access better (more effective and with milder adverse reactions) treatment.
There is a clear case for the need for mental health research. This research often needs clinical trials to be performed, to safely and rigorously identify and test better treatments for those suffering from mental disorders. Without mental ill-health sufferers who are willing to participate in clinical trials such as the ones performed at the BRC, no progress can be made.
Participant recruitment to clinical trials
The NIHR Mental Health BRC (http://brc.slam.nhs.uk/) is one of eleven NIHR funded Biomedical Research Centres throughout England. It is hosted and run by the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King’s College London and the South London and Maudsley Foundation Trust (SlaM). Also known as the Maudsley BRC, it values those who are willing to give up their time to participate in the clinical trials they run and are eager to show their appreciation. Prospective participants are given the fullest information about what they can expect from a clinical trial and what it will require of them before they sign a consent form. In return they are kept fully informed of their progress during the clinical trial process and remunerated for their time and any travel expenses incurred. If they wish to withdraw from the trial at any time they may do so, as enshrined in law through acceptance of the Helsinki Declaration [8]. On withdrawal from participation in a clinical trial, a patient will be offered the standard care/treatment which applies normally to any patient in that situation.
In many cases participants have the option of receiving information about the outcomes of the trial when they are finalised. Everyone who participates helps towards developing a better understanding of mental disorder and how it may be more effectively treated.
Public and patient recruitment to clinical trials is one of the main barriers to the implementation of clinical trials. Many clinical trials fail to recruit the desired number of public and/or patient participants [9]. According to research conducted by the author for the King’s Clinical Trials Unit (KCTU), IoPPN, King’s College London and, there are several causal factors all of which are identified in the published paper ‘Promoting Factors and Barriers to Participation in Early Phase Clinical Trials’ [10], the main three being:
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cultural resistance in the NHS (Often perceived as a consequence of the relational dynamics between academics and clinicians)
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rapid turnover of clinical teams and patients
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as gatekeepers, clinicians may seek to protect people for whom they provide care from the perceived burden of research participation and/or an intervention perceived to be futile for an intractable condition.
Furthermore clinical trials need to recruit to capacity as, in general larger numbers of participants leads to more representative and informative statistical analysis of clinical trial data and thereby, potentially the identification and development of more effective psychiatric treatments [11]. It is often important for clinical trial participants to be of a diverse nature whilst still conforming the exclusion/inclusion trial specific criteria. Again this is optimised by maximising recruitment and retention to clinical trials.
The BRC had identified a paucity of referrals from clinicians as impacting negatively on recruitment to clinical trials. This was viewed as a longstanding problem and seemingly resistant to resolution. It was decided to improve the BRC website in order to attract more public and patient awareness of and interest in participating in clinical trials and thereby encourage direct expressions of interest in clinical trial participation. As all prospective trial participants are screened thoroughly before being given the opportunity to consent to participate, the absence of a clinical referral would not affect patient (or healthy volunteer) safety or well-being.
The UK Clinical Trials Gateway is the NIHR-hosted website that allows people to search for information about clinical trials in the UK (http://www.ukctg.nihr.ac.uk/default.aspx).
However according to a public survey [12] conducted by the AMRC - Association of Medical Research Charities (designed to ascertain the accessibility of the UK Clinical Trials Gateway and information on currently recruiting clinical trials:
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80 % had not heard of UKCTG before receiving the survey.
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Only 28 % had taken part in a clinical trial.
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38 % said they knew little or nothing about clinical trials and would like a clear and reliable source of information to learn more; 56 % said it would help them or someone they care for explore opportunities to take part in a clinical trial now or in the future.
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64 % said they would like to find out about trials recruiting in their local area.
This indicates that there are significant numbers of people who want to know more about clinical trials and how to find one relevant to their needs.
The survey was carried out through surveymonkey and a link distributed via email to a range of patient groups and networks. It was also posted on a number of websites including the NIHRs Clinical Research Network, INVOLVE and UKCTG. The survey ran for the whole of July 2012.
As a result of these findings the AMRC made the following recommendations to help the UKCTG better reflect the priorities of people interested in finding out about, and taking part in, clinical trials:
Vision and strategy - Going forward the UKCTG needs a more patient-focused strategy so that it meets their needs as well as the UK research community’s.
Awareness and promotion - the site needs renaming and made easier to find by patients searching for information. It needs better promotion by the NHS, by charities and patient groups, research funders and other organisations.
Public Involvement/User Panel - a user panel should be involved in the future development of the site, including advising on the best way to implement the above recommendations and to build up a knowledge base of public experience of using the UKCTG and taking part in trials, to inform patients and the wider research community.
In order to resolve the BRC’s public and patient clinic trial recruitment difficulties the researcher (a member of the BRC’s Psychosis Clinical Academic Group) was appointed to spear-head an initiative to improve access to information and participation in currently recruiting clinical trials. The researcher recruited the author to the initiative after the latter expressed an interest in being involved and proffered some of her own knowledge and research findings on the issue.
At the time the author began working with the researcher, she was aware of the AMRC survey, its findings and recommendations. This persuaded the researcher and author that in order to enhance clinical trial recruitment at the BRC it would require a dedicated online clinical trial recruitment portal with the following features:
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Vision and Strategy – The clinical trial recruitment portal would feature current, clear, up to date, easy to understand information on the nature and purpose of clinical trials and experience of participating in a clinical trial.
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Awareness and promotion - In order for the portal to become known to interested patients and members of the public, it would be advertised on major mental health charity/research websites, e.g. MQ, Rethink, NSUN, etc.
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Patient Use/Involvement Panel - The entire function and structure of the online clinical trial recruitment portal would be discussed with the BRC Service User Advisory Group (SUAG) of which the author is a member, and their recommendations incorporated into the beta version of the online recruitment portal. This occurred on 05/08/15. This group remains a valuable consultation resource for the online clinical trial recruitment portal.