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].

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.

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).

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.

March-April 2015

The researcher and author meet to discuss how to improve the clinical trial pages of the website. The author gives information on national and global research findings that service users find it hard to access information on recruiting clinical trials and the clinical trial process [12, 13].

21/04/15

The researcher and author meet with the manager of the BRC to discuss how to modify and improve the clinical trial pages of the BRC website.

May-June 2015

The author in consultation with her colleague, the researcher, builds a beta version of an online clinical trials recruitment portal for the BRC as a means of conveying their shared vision of how to promote public and patient participation. The author uses Joomla, an open-source content management system to construct the portal [14].

08/06/15

The researcher and author meet with a senior researcher in the NIHR Mental Health BRU (Biomedical Research Unit) to discuss the active online recruitment portal for senior researcher’s PROTECT study of ageing in adults over 50 years old [15]. The PROTECT study portal has proved very successful in recruiting patients to participate. There is consideration of the various features and functionality of the PROTECT study portal together with the possibility of extending the PROTECT study portal to the BRC or re-using the code to create an independent online platform. The author after later consultation and discussion with the researcher, modifies the beta online clinical trial recruitment portal to include a template functionality modelled on the PROTECT study portal. This would allow research groups to develop their own study specific online recruitment portal, and link it to the main BRC online recruitment portal.

10/06/15

Presentation of the beta version of the clinical trials recruitment portal at the Clinical Disorders Cluster Group Board Meeting with subsequent discussion/feedback session. The consensus view at the meeting is that the beta version is potentially very useful in encouraging participation in clinical trials and that its formal development should be explored together with service user and carer input. Subsequently the author seeks competitive bids sought for the contract for the final version.

01/07/15

The researcher and author meet with prospective developers for the final version of the clinical trials recruitment portal. They discuss possible design specification and the associated cost of developing and maintaining a final version of the recruitment portal. Quotes for the work are requested.

July-August 2015

Feedback on beta website requested from the RCPsych and national mental health charities (Mind, Sane, Rethink, MQ, McPin, NSUN) and their associated service user groups/membership. The organisations send out (by email and post) details of the intended purpose of the beta website to their members and service user groups, together with a hyperlink to the website and requests for feedback to be emailed or posted directly to the author. The author receives the feedback which is considered and used to amend and extend the beta website. Overall the feedback is complimentary, but there are requests for a clarification of acronyms featured on the website and a clearer classification of the kinds or clinical trials run by the BRC. The author acts to clarify and minimise the use of acronyms and regroups the list of currently recruiting clinical trials at the BRC according to the specific mental disorders concerned. A member of the RCPysch’s Carers’ Forum reports by email that the beta website is easy to navigate and requests that a summarised guideline to the process of participation in clinical trials is provided. This is actioned at once by SM. MQ, McPin and NSUN report they will be agreeable to consider hosting a link to the final version of the online recruitment portal on their respective websites on reviewing the finished branded NIHR Mental Health BRC online recruitment portal for themselves. Mind, Sane and Rethink, reply that they only advertise their own branded products on their website but they are agreeable to the NIHR Mental Health BRC posting updates and references to the final online recruitment portal on their respective Facebook pages.

July-August 2015

Feedback on beta website requested from all BRC principal investigators. The feedback, is uniformly positive from those who respond. This feedback, together with that obtained via the various mental health charities, is collated to present and discuss at the Experimental Medicine & Clinical Trials Theme Meeting on 07/09/15.

05/08/15

Consultation with the NIHR Mental Health BRC Service User Advisory Group to gain more patient and carer views on the online clinical trial recruitment portal; the information and services it should provide and how these might best be presented using the portal. Strong interest is expressed in the online recruitment portal and the overall feedback is positive. No significant changes are requested, but the importance of all information on upcoming and currently recruiting clinical trials being up to date is emphasized.

07/09/15

Presentation of the beta version of the online clinical trial recruitment portal at the Experimental Medicine and Clinical Trials Theme Meeting together with associated feedback as detailed above. Approval is given for a final version of the portal to be created using the services of a professional software engineer and incorporated into the main NIHR Mental Health BRC website, providing funding can be found.

22/09/15

Presentation of the beta version of the online clinical trial recruitment portal at the Clinical Disorders Cluster Group Board Meeting together with associated feedback. There is subsequent discussion/feedback session. Approval for a final version of the portal to be created using the services of a professional software engineer and incorporated into the main NIHR Mental Health BRC website is confirmed, providing funding can be found.

01/10/15

Meeting of the author and researcher with the manager of the BRC. The beta version of the online clinical trial recruitment portal with all modifications completed is presented and funding for the final NIHR Mental Health BRC branded version discussed. It is agreed that the contract for the final version will be awarded to Limetree Products Ltd [16]. It is also agreed that the final version will be paid for by the core BRC funding as part of a wider project to update and modify the entire BRC website (to enhance its accessibility and relevance). Thus funding for the final (branded) version of the online clinical trial recruitment portal is secured.