Making the Leap: from Experimental Psychopathology to Clinical Trials

One important aim of experimental psychopathology research is to inform development of new interventions derived from basic science. However, testing whether a newly developed intervention is in fact effective requires moving from experimental studies to clinical trials, and this transition can pose many problems. These problems stem not only from the inherent complexity of even the simplest clinical trial, but also from differences between experimental psychopathology and clinical trial research that may not always be obvious to researchers immersed in only one of these specialist areas. In this paper we explore some of these complexities, and discuss when a clinical trial may, or may not be, the best next step in the translational process. We then consider some of the ins and outs of clinical trials methodology, from design and planning through to reporting, with the aim of providing a guide for experimental psychopathology researchers thinking of making the leap from their experimental studies of mechanisms to clinical trials of novel interventions. We hope that this can help increase the chance of successful clinical translation and novel treatment development from basic science.

Exploring the inclusion of under-served groups in trials methodology research: an example from ethnic minority populations’ views on deferred consent

Background Deferred consent is used to recruit patients in emergency research, when informed consent cannot be obtained prior to enrolment. This model of consent allows studies to recruit larger numbers of participants, especially where a surrogate-decision maker may be unavailable to provide consent. Whilst deferred consent offers the potential to promote trial diversity by including under-served groups, it is ethically complex and views about its use amongst these populations require further exploration. The aim of this article is to build upon recent initiatives to improve inclusivity in trials, such as the NIHR INCLUDE project, and consider whether trials methodology research is inclusive, focusing on ethnic minority populations’ attitudes towards the use of deferred consent. Main text Findings from the literature suggest that research regarding attitudes toward recruitment methods like deferred consent largely fail to adequately represent ethnic minorities. Many studies fail to report the composition of patient samples or conduct analyses on any differences between specific patient groups. In those that do, the categorisation of ethnic groups is ambiguous. Frequently diversely different groups are considered as more homogenous than they are. Whilst deferred consent is deemed generally acceptable, analysis of patient sub-groups shows that this attitude is not universal. Those from racial and ethnic minority backgrounds reported higher levels of unacceptability, which was impacted by previous first or second-hand experience of its use and historical mistrust in research. However, whilst deferred consent was found to increase the numbers of black participants enrolled in some trials, their over-enrolment in other trials may raise further concerns. Conclusions Inclusivity in clinical trials is important, as highlighted by the COVID-19 pandemic. To improve this, we must ensure that methodological studies such as those exploring attitudes to research are inclusive. More effort is needed to understand the views of under-served groups, such as ethnic minorities, toward research in order to improve participation in clinical trials. Our findings echo those from the INCLUDE project, in that better reporting is needed and increasing the confidence of ethnic minority groups in research requires improving representation throughout the research process. This will involve diversifying research teams and ethics committees.

Exploring the Inclusion of Under-Served Groups in Trials Methodology Research: An Example from Ethnic Minority Populations’ Views on Deferred Consent

Background: Deferred consent is used to recruit patients in emergency research, when informed consent cannot be obtained prior to enrolment. This model of consent allows studies to recruit larger numbers of participants, especially where a surrogate-decision maker may be unavailable to provide consent. Whilst deferred consent offers the potential to promote trial diversity by including under-served groups, it is ethically complex and views about its use amongst these populations requires further exploration. The aim of this article is to build upon recent initiatives to improve inclusivity in trials, such as the NIHR INCLUDE project, and consider whether trials methodology research is inclusive, focusing on ethnic minority populations’ attitudes towards the use of deferred consent.Main text: Findings from the literature suggest that research regarding attitudes toward recruitment methods like deferred consent largely fail to adequately represent ethnic minorities. Many studies fail to report the composition of patient samples or conduct analyses on any differences between specific patient groups. In those that do, the categorisation of ethnic groups is ambiguous. Frequently diversely different groups are considered as more homogenous than they are. Whilst deferred consent is deemed generally acceptable, analysis of patient sub-groups shows that this attitude is not universal. Those from racial and ethnic minority backgrounds reported higher levels of unacceptability, which was impacted by previous first or second-hand experience of its use and historical mistrust in research. However, whilst deferred consent was found to increase the numbers of black participants enrolled in some trials, their over-enrolment in other trials may raise further concerns. Conclusions: Inclusivity in clinical trials is important, as highlighted by the COVID-19 pandemic. To improve this, we must ensure that methodological studies such as those exploring attitudes to research are inclusive. More effort is needed to understand the views of under-served groups, such as ethnic minorities, toward research in order to improve participation in clinical trials. Our findings echo those from the INCLUDE project, in that better reporting is needed and increasing the confidence of ethnic minority groups in research requires improving representation throughout the research process. This will involve diversifying research teams and ethics committees.

Impact of a Collaborative Clinical Trials Methodology Course on Trainees’ Funding and Clinical Trials Activity

Introduction Clinical trials are challenging, and many junior investigators lack the skills to move through the phases in a coherent way. To address this issue in the clinical neurosciences, the NINDS Clinical Trials Methodology Course (CTMC) was created through cross university collaborations to provide junior investigators with relevant education and training to promote well-designed clinical trials. This study aims to explore the impact of CTMC by determining the trajectory of NIH funding and clinical trials activity in trainees after completion of the course. Methods The online databases NIH RePORTER and ClinicalTrials.gov were searched respectively to determine NIH funding and clinical trials activity of each CTMC trainee between 2014-2017. Data was collected on the Project Start Date of the first NIH grant and the Study Start Date of the first non-withdrawn clinical trial each trainee had after taking CTMC. Grants or trials prior to CTMC were noted. The date of a trainee’s CTMC was designated as January 1 st of the year following course completion. Time until grant or clinical trial was calculated as the difference between the Project/Study Start Date and the trainee’s CTMC date. Results and Discussion There were 131 CTMC trainees between 2014-2017. As of early 2019, 23.7% of these trainees received a NIH grant and 43.5% became involved in a clinical trial after the course. Excluding those with prior experience, 11.5% of all trainees received their first-ever NIH grant and 27.5% became involved in their first-ever clinical trial following completion of CTMC. For all trainees who received a NIH grant or became involved in a clinical trial after the course, the median times to these achievements were 1.1 years (IQR 0.5-1.9 years) and 1.2 years (IQR 0.6-2.2 years), respectively. These results suggest that completing CTMC may help promote successful funding and clinical trials by junior investigators.

An examination of the effects of a patient-designed-and-informed participant information sheet in comparison with a standard, researcher-designed information sheet on recruitment, retention and understanding: Protocol for a study-within-a-trial

Background: This protocol describes a double-blind, randomised non-inferiority study-within-a-trial (SWAT), comparing the effects of a patient-designed-and-informed participant information sheet with a standard, researcher-designed participant information sheet on recruitment, retention, decision certainty, participant information sheet understanding and likeability. The SWAT is part of a larger trial that aims to evaluate the feasibility and preliminary efficacy of a cognitive occupation-based programme for people with MS (COB-MS) on cognitive and daily functioning for people with multiple sclerosis. Methods: During the study, 120 people with multiple sclerosis will be randomly allocated to one of the two groups, where they will either receive a standard participant information sheet or a patient-designed participant information sheet. Recruitment and retention will be analysed, as well as decision certainty, likability and understanding. Discussion: Results will provide recommendations for recruitment, consent and retention for future trials, as well as shed some light on the factors influencing the understanding and likeability of a trial’s participant information sheet. Recommendations will also be made regarding patient and public involvement in developing and/or aiding the development of participant information sheets. Registration: SWAT: Northern Ireland Hub for Trials Methodology Research SWAT Repository Store (SWAT105). COB-MS trial: ISRCTN11462710.

An examination of the effects of a patient-designed-and-informed participant information sheet in comparison with a standard, researcher-designed information sheet on recruitment, retention and understanding: Protocol for a study-within-a-trial

Background: This protocol describes a double-blind, randomised non-inferiority study-within-a-trial (SWAT), comparing the effects of a patient-designed-and-informed participant information sheet with a standard, researcher-designed participant information sheet on recruitment, retention, decision certainty, participant information sheet understanding and likeability. The SWAT is part of a larger trial that aims to evaluate the feasibility and preliminary efficacy of a cognitive occupation-based programme for people with MS (COB-MS) on cognitive and daily functioning for people with multiple sclerosis. Methods: During the study, 120 people with multiple sclerosis will be randomly allocated to one of the two groups, where they will either receive a standard participant information sheet or a patient-designed participant information sheet. Recruitment and retention will be analysed, as well as decision certainty, likability and understanding. Discussion: Results will provide recommendations for recruitment, consent and retention for future trials, as well as shed some light on the factors influencing the understanding and likeability of a trial’s participant information sheet. Recommendations will also be made regarding patient and public involvement in developing and/or aiding the development of participant information sheets. Registration: SWAT: Northern Ireland Hub for Trials Methodology Research SWAT Repository Store (SWAT105). COB-MS trial: ISRCTN11462710.

Identifying important barriers to recruitment of patients in randomised clinical studies using a questionnaire for study personnel

Background Many randomised controlled trials (RCT) fail to meet their recruitment goals. Study personnel play a key role in recruitment. The aim of this study was to identify successful strategies that study personnel consider to be important in patient recruitment to RCT. Methods We constructed a questionnaire based on the literature, discussions with colleagues and our own experience as trialists. The survey was named “What is Important for Making a Study Successful questionnaire” (WIMSS-q). Our target group was the study personnel in the ongoing EFFECTS study. The questionnaire was sent out electronically to all physicians and nurses (n = 148). Success factors and barriers were divided according to patient, centre and study level, respectively. Results Responses were received from 94% of the study personnel (139/148). The five most important factors at centre level for enhancing recruitment were that the research question was important (97%), a simple procedure for providing information and gaining consent (92%), a highly engaged local principal investigator and research nurse (both 87%), and that study-related follow-ups are practically feasible and possible to coordinate with the clinical follow-up (87%). The most significant barrier at the local centre was lack of time and resources devoted to research (72%). Important patient-related barriers were fear of side effects (35%) and language problems (30%). Conclusions For recruitment in an RCT to be successful, the research question must be relevant, and the protocol must be simple and easy to implement in the daily routine. Trial registration The protocol for this study was registered at the Northern Ireland Hub for trials methodology research (SWAT ID 64). The EFFECTS study has EudraCT number 2011–006130-16 and was registered 17 February 2016 at ClinicalTrials.gov number NCT02683213.