1. Introduction to the PrEgabalin Lidocaine Capsaicin Neuropathic Pain (PELICAN) Pragmatic Trial
chronic pain, overdose
RECRUITMENT, ADVERSE EVENTS, RECRUITMENT, ADVERSE EFFECTS, SYNDROMES, CHRONIC PAIN
Moderate to severe chronic pain occurs in 19% of European adults, significantly affecting the quality of their social and professional lives [The PELICAN study was a randomized, multicenter, comparative pragmatic trial that aimed to examine topical versus systemic treatment in adult patients with LNP syndromes. Systemic treatment options are often linked to side effects, whereas the topical route offers significant advantages. Notably, only a small fraction of the dose administered topically reaches the systemic circulation, thereby reducing the risk of systemic adverse effects, drug-drug interactions, and overdose. The Belgian Healthcare Knowledge Center (KCE) funded the PELICAN study under their KCE Trials program (see for more details on the program Recruitment for the PELICAN trial commenced in December 2018. Unfortunately, the recruitment of patients was extremely slow, and despite several actions to address this, the enrollment rate remained insufficient. Finally, and in mutual agreement, the project funder and sponsor decided to stop the trial on March 30, 2020, because of these inclusion difficulties and the COVID-19 pandemic. By the time of the study's premature closure, 32 patients had signed the informed consent form and had been randomized into 10 of the participating centers. All data have been registered in a synopsis report which can be accessed at One of the most challenging findings was the high discontinuation rate observed in both topical treatment options by week 26 (100% for lidocaine and 77.8% for capsaicin). This finding was unexpected, and unfortunately, the premature discontinuation of the trial prevented us from further identifying possible explanations for this finding. Regarding the observed safety profile, systemic treatment with pregabalin appeared to induce more adverse events than lidocaine treatment. Interestingly, the topical application of capsaicin patches seemed to also induce a substantial number of systemic adverse events.Despite the observation of some interesting trends, in the end, there were insufficient data to draw any conclusions from the study, creating the need for a follow-up qualitative study to investigate the reasons for the unanticipated failure of this well-prepared trial. The funder and study team's main aspiration was to determine the reasons behind the recruitment failure through a scientifically based methodology. When a clinical trial is prematurely discontinued, it is essential that stakeholders take the right steps to ensure that lessons are learned, and trust in clinical research is maintained. However, this is often overlooked, leading to a lack of evidence on how recruitment failure occurs and its prevention. A recent study that investigated this delicate matter concluded that the decision to publish findings from a discontinued clinical trial should not rest solely on individual investigators but rather should be part of a systemic approach [