Discontinuation of the PACE Plus trial: problems in patient recruitment in general practice

Abstract

BackgroundThe PACE Plus trial was a multi-center, double-blinded, superiority randomized controlled trial (RCT) conducted in patients from Dutch general practice to investigate the efficacy of paracetamol and NSAIDs in acute non-specific low back pain (LBP). Because insufficient numbers of patients could be recruited (only four out of the required 800 patients could be recruited over a period of 6 months), the trial was prematurely terminated in February 2017, 6 months after the start of recruitment. This article aims to transparently communicate the discontinuation of PACE Plus and to make recommendations for future studies.MethodsGeneral Practitioners (GPs) from 36 participating practices received a one-question survey in which they were asked to give the three most important factors that in their opinion contributed to failure of patient recruitment.ResultsGPs of 33 out of 36 (92%) participating practices sent a response. A total of 81 factors were reported. These have been categorized into patient factors (26 out of 81 comments, 32%), GP factors (39 out of 81 comments, 48%) and research factors (16 out of 81 comments, 20%).DiscussionPatient recruitment in the PACE Plus trial may have failed due to inefficient medication distribution, recruitment of incident rather than prevalent cases, a design that was too complicated, adequate self-management of LBP, patient expectations different from the trial’s scope and lack of time of participating GPs. Substantial differences in design may explain why the preceding PACE trial did manage to successfully complete patient recruitment.ConclusionAlthough the PACE Plus trial was terminated as a result of insufficient patient inclusion, the research questions addressed in this trial remain relevant but unanswered. We hope that lessons learned from the discontinuation of PACE Plus and corresponding recommendations may be helpful in the design of upcoming research projects in LBP in general practice.Trial registrationDutch Trial Registration NTR6089, registered September 14th 2016.

Inferential reproduction analysis demonstrated that “paracetamol for acute low back pain” trial conclusions were reproducible

“…For this reanalysis, the predefined and published analysis plan from the PACE Plus trial was used [16]. The PACE Plus trial was a randomized, placebo-controlled clinical trial that aimed to reproduce the results obtained in the PACE trial; however, this trial was discontinued because of insufficient patient recruitment [16,17]. As the groups and outcomes were similar but not identical between PACE and PACE Plus, we present primary and secondary outcomes of the current reproduction analysis here.…”

“…[8]. Another RCT evaluating the result of the PACE trial (called the PACE Plus trial) was discontinued in 2017 because of insufficient recruitment of participants [16,17]. The primary outcome in the PACE trial was time until recovery from LBP, but this outcome is not among the outcome domains most relevant to patients with LBP [18].…”

STeroids Against Radiculopathy (STAR) trial: a statistical analysis plan

“…Issues that affected slow patient accrual were the fact that (according to their guidelines) ( https://richtlijnen.nhg.org/standaarden/lumbosacraal-radiculair-syndroom ) Dutch general practitioners typically wait at least 6 weeks before referring patients with sciatica to a hospital; the fact that there were only 2 participating centres, and the fact that patients who believe in the superiority of epidural steroid injection over conservative treatment experience difficulty with being randomized and prefer active treatment with an epidural steroid injection. This is a well-known problem in back pain research [ 37 , 38 ], but it will likely negatively affect the generalizability of our results to other (Dutch) sciatica patients and will result in the study being slightly underpowered for pain intensity and global perceived effect, but not for physical functioning.…”

Retrospective Medical Record Research: Reflections of A Unsponsored Researcher

“…However, with General Practices in crisis [25], the workload has become more complex and intensive without the funds to support the workforce and the complex infrastructure required [26]. As the pressure has grown, patient experience has also deteriorated [27][28][29][30][31][32][33][34][35][36], with a knock-on effect that the recruitment of practices for research that would contribute in improving patients'experience has become almost impossible. We advocate for more funding and enlightenment in terms of what research means to healthcare development, on how patient notes can be made accessible for those with appropriate ethical approvals in place.…”