Louise Dudley

From plans to actions in patient and public involvement: qualitative study of documented plans and the accounts of researchers and patients sampled from a cohort of clinical trials

Patient and public involvement (PPI) in research is increasingly required, although evidence to inform its implementation is limited. Objective Inform the evidence base by describing how plans for PPI were implemented within clinical trials and identifying the challenges and lessons learnt by research teams. Methods We compared PPI plans extracted from clinical trial grant applications (funded by the National Institute for Health Research Health Technology Assessment Programme between 2006 and 2010) with researchers’ and PPI contributors’ interview accounts of PPI implementation. Analysis of PPI plans and transcribed qualitative interviews drew on the Framework technique. Results Of 28 trials, 25 documented plans for PPI in funding applications and half described implementing PPI before applying for funding. Plans varied from minimal to extensive, although almost all anticipated multiple modes of PPI. Interview accounts indicated that PPI plans had been fully implemented in 20/25 trials and even expanded in some. Nevertheless, some researchers described PPI within their trials as tokenistic. Researchers and contributors noted that late or minimal PPI engagement diminished its value. Both groups perceived uncertainty about roles in relation to PPI, and noted contributors’ lack of confidence and difficulties attending meetings. PPI contributors experienced problems in interacting with researchers and understanding technical language. Researchers reported difficulties finding ‘the right’ PPI contributors, and advised caution when involving investigators’ current patients. Conclusions Engaging PPI contributors early and ensuring ongoing clarity about their activities, roles and goals, is crucial to PPIs success. Funders, reviewers and regulators should recognise the value of preapplication PPI and allocate further resources to it. They should also consider whether PPI plans in grant applications match a trials distinct needs. Monitoring and reporting PPI before, during and after trials will help the research community to optimise PPI, although the need for ongoing flexibility in implementing PPI should also be recognised.

Patient and public involvement in the early stages of clinical trial development: a systematic cohort investigation.

Background Randomised controlled trials (RCTs) are considered particularly likely to benefit from patient and public involvement (PPI). Decisions made by professional researchers at the outset may go on to have a significant impact on the potential for PPI contributions. Objective To increase knowledge of PPI within the early development of RCTs by systematically describing the reported level, nature and acceptability of proposed PPI to the funders. Methods Documentation from the outline application process for all RCTs that received funding from the Health Technology Assessment (HTA) Programme 2006–2010 was requested. For each application, data were extracted on trial characteristics, references to PPI in the development of the outline application and funding Board feedback, and plans for PPI in the full application and after the trial was funded. Results 110 applications were eligible with outline applications available for 90 (82%). The cohort covered a wide range of interventions and conditions. 54% (49/90) provided some information about PPI. 26 (28.9%) indicated PPI within the development of the outline application itself; 32 (35.6%) planned involvement in the full application and 43 (48%) once the trial was funded. Recruitment at diagnosis and surgical interventions were less likely to describe PPI. Blinded trials and trials in which participants may receive placebo only, more frequently described PPI activity. The HTA commissioning Board feedback rarely referred to PPI. Conclusions Incorporation of PPI within the development of the outline application or specification of plans for future involvement was low. Funder requests for applicants to provide information on PPI and justification for its absence should be welcomed but further research is needed to identify the impact of this on its contributions to research. Comments on PPI by reviewers should be directional rather than state that an increase is required. Challenges facing applicants in initiating PPI prior to funding need to be addressed.

A little more conversation please? Qualitative study of researchers’ and patients’ interview accounts of training for patient and public involvement in clinical trials

BackgroundTraining in patient and public involvement (PPI) is recommended, yet little is known about what training is needed. We explored researchers’ and PPI contributors’ accounts of PPI activity and training to inform the design of PPI training for both parties.MethodsWe used semi-structured qualitative interviews with researchers (chief investigators and trial managers) and PPI contributors, accessed through a cohort of clinical trials, which had been funded between 2006 and 2010. An analysis of transcripts of audio-recorded interviews drew on the constant comparative method.ResultsWe interviewed 31 researchers and 17 PPI contributors from 28 trials. Most researchers could see some value in PPI training for researchers, although just under half had received such training themselves, and some had concerns about the purpose and evidence base for PPI training. PPI contributors were evenly split in their perceptions of whether researchers needed training in PPI. Few PPI contributors had themselves received training for their roles. Many informants across all groups felt that training PPI contributors was unnecessary because they already possessed the skills needed. Informants were also concerned that training would professionalise PPI contributors, limiting their ability to provide an authentic patient perspective. However, informants welcomed informal induction ‘conversations’ to help contributors understand their roles and support them in voicing their opinions. Informants believed that PPI contributors should be confident, motivated, intelligent, focussed on helping others and have relevant experience. Researchers looked for these qualities when selecting contributors, and spoke of how finding ‘the right’ contributor was more important than accessing ‘the right’ training.ConclusionsWhile informants were broadly receptive to PPI training for researchers, they expressed considerable reluctance to training PPI contributors. Providers of training will need to address these reservations. Our findings point to the importance of reconsidering how training is conceptualised, designed and promoted and of providing flexible, learning opportunities in ways that flow from researchers’ and contributors’ needs and preferences. We also identify some areas of training content and the need for further consideration to be given to the selection of PPI contributors and models for implementing PPI to ensure clinical trials benefit from a diversity of patient perspectives.

Outcome of Azacitidine Therapy in Acute Myeloid Leukemia Is not Improved by Concurrent Vorinostat Therapy but Is Predicted by a Diagnostic Molecular Signature.

Purpose: Azacitidine (AZA) is a novel therapeutic option in older patients with acute myeloid leukemia (AML), but its rational utilization is compromised by the fact that neither the determinants of clinical response nor its mechanism of action are defined. Co-administration of histone deacetylase inhibitors, such as vorinostat (VOR), is reported to improve the clinical activity of AZA, but this has not been prospectively studied in patients with AML. Experimental Design: We compared outcomes in 259 adults with AML (n = 217) and MDS (n = 42) randomized to receive either AZA monotherapy (75 mg/m2 × 7 days every 28 days) or AZA combined with VOR 300 mg twice a day on days 3 to 9 orally. Next-generation sequencing was performed in 250 patients on 41 genes commonly mutated in AML. Serial immunophenotyping of progenitor cells was performed in 47 patients. Results: Co-administration of VOR did not increase the overall response rate (P = 0.84) or overall survival (OS; P = 0.32). Specifically, no benefit was identified in either de novo or relapsed AML. Mutations in the genes CDKN2A (P = 0.0001), IDH1 (P = 0.004), and TP53 (P = 0.003) were associated with reduced OS. Lymphoid multipotential progenitor populations were greatly expanded at diagnosis and although reduced in size in responding patients remained detectable throughout treatment. Conclusions: This study demonstrates no benefit of concurrent administration of VOR with AZA but identifies a mutational signature predictive of outcome after AZA-based therapy. The correlation between heterozygous loss of function CDKN2A mutations and decreased OS implicates induction of cell-cycle arrest as a mechanism by which AZA exerts its clinical activity. Clin Cancer Res; 23(21); 6430–40. ©2017 AACR.

Evidence base for patient and public involvement in clinical trials (EPIC)

Background Patient and public involvement (PPI), inclusion of members of the public as active partners in the research process, can be a requirement of research funding. Limited evidence has suggested that clinical trials may be particularly likely to benefit from PPI. There is a lack of critical assessment of PPI and suggestions in the literature of selective reporting of its benefits. This study aims to increase the knowledge of PPI in clinical trials by systematically investigating how it is approached within a cohort of public funded randomised trials in the UK. Methods Documentation from the application process for all randomised trials funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme between 2006 and 2010 were obtained. Data relating to PPI activity and how these plans were assessed within the peer review process were extracted. Results Documentation to allow details of planned PPI activity to be extracted were available in 107 RCTs. PPI representation was not described in 15% with representation on TSCs, DMCs, and TMGs described in 53%, 8%, and 12% of applications respectively. A consultancy approach was described in 26%. Of the 515 reviewers comments across the trials only 211(41%) commented on PPI plans. The majority repeated the PPI plans from the application rather than commenting on their suitability. Conclusions Research applicants frequently describe PPI but reviewers seem unable to comment on suitability of the approach. Evidence of impact is needed to inform future approaches for applicants and peer reviewers.

Realising the potential of patient and public involvement to make a difference: what can trial teams do?

Results We interviewed 21 chief investigators, 10 trial managers and 17 PPI contributors from 28 trials. Over half the informants indicted that PPI had made a difference, influencing either an aspect of a trial, or how trialists felt about a trial. Informants described how PPI’s impact depended on the quality of chief investigators’ goals and plans for PPI, the quality of relationships between trialists and PPI contributors, and stage at which PPI involvement was implemented. Including PPI contributors in responsive (e.g. advisory groups) and managerial (e.g. trial management groups) roles was thought more likely to achieve impact than oversight roles (e.g. trial steering committees).