3. Findings
neuropathic pain, anxiety, Neuropathic pain, pain, PHN
PHN, RECRUITMENT, INFILTRATION, RECRUITMENT, SYNDROMES
The qualitative study revealed several different reasons for the low recruitment rate. One of the reasons was the somewhat limited clinical trial experience in approximately half of the participating pain centers. Responses varied that centers performed one to eight clinical trials every 5 years. Furthermore, a significant proportion of these studies were related to somatic or mixed (neuropathic-somatic) pain syndromes rather than neuropathic pain alone. Neuropathic pain studies have almost exclusively been limited to either PHN or DPN. This shows that research experience regarding LNP conditions is rather limited in Belgium. Nevertheless, 33% of the responding centers claimed to have previously conducted one or more LNP-specific studies. Most research experiences were in the context of pharmacological studies, and these studies were dated to at least 3 years ago. In addition, two-thirds of the responding pain centers claimed to have experience in conducting pragmatic trials, but during the interviews, it became clear that while pragmatic studies are well known, some studies are mistakenly defined as pragmatic by investigators. Therefore, actual experience with pragmatic studies is lower than initially assumed.Another possible reason for the low recruitment lies in the nonavailability of dedicated study staff. Sixteen of the responding pain centers declared that they had specific staff available to conduct clinical trials. However, it was discovered that this availability was mainly on a part-time basis. The other centers, however, did not have any dedicated study staff. This is understandable considering the small number of algology (pain treatment) clinical studies recently conducted, but this significantly negatively impacts the recruitment of patients in clinical studies.Furthermore, it became clear that many centers have no specific treatment protocols available for LNP. When different options were presented during the digital survey, 83.33% of the responding pain centers identified the following flowchart as their first-choice treatment approach for LNP conditions: (1) systemic medication (analgesics), (2) topical treatment, (3) infiltration, (4) neuromodulation, and (5) spinal administration of analgesics. The different flow charts that were proposed for review are detailed in Recruitment appeared slow from the outset and relied primarily on internal referrals. This raises the question as to why there are so few external referrals to pain centers. Interviews revealed that general practitioners (GPs) tend to treat LNP complaints themselves, mostly applying systemic treatment options (such as pregabalin). Thus, many patients had already completed pregabalin treatment before referral to the pain center, impacting their inclusion into the study protocol. In addition, patients tend to remain in primary care or related specialties for a longer period, so late referral also contributed to the low recruitment rate, with many patients falling outside the set time frames for the duration of pain symptoms. Such a high level of late referral had not been anticipated by the PELICAN study team or local investigators during the feasibility studies.Notably, 50% of the patients who were prescreened refused to participate in the study—higher than initially anticipated—due to patients' apprehension about financial implications. This is because, initially, only the systemic option (pregabalin) was reimbursed. During the recruitment period, the high concentration capsaicin patch, was reimbursed. Patients could now choose a fully reimbursed topical treatment option, causing a significant number of patients (general estimate across the different pain centers: at least 30 patients) to become reluctant to participate and rather “safely” opt for the reimbursed capsaicin treatment.Participating centers also mentioned insufficient reimbursement for nursing activities related to the application of the concentrated capsaicin patches. Treatment with topical capsaicin requires a significant time investment from pain nurses, without any compensation or lump sum reimbursement. Although a substantial additional compensation was provided by the study protocol for the execution of capsaicin treatment by the funder, this was still perceived as too little by some participating centers. Undoubtedly, this had an additional negative impact on recruitment. Interestingly enough, a similar situation has arisen in routine clinical practice. After the capsaicin patches were reimbursed by the social security system in Belgium, uptake in clinical practice remained limited due to nonreimbursement for nursing activities. The main reasons for recruitment failure in the PELICAN study are described in more detail in A specialized monitoring system was developed so that patients and investigators could submit all data and assessments related to the PELICAN study digitally. The PELICAN@home platform—a primary source—was hosted on servers within the central server facility at the Antwerp University Hospital. During the trial, feedback was received from participating pain centers that some patients faced difficulties in completing the digital assessments. Therefore, the study team ensured that all assessments were also available on paper (even in different languages). Nevertheless, during the digital survey, half of the PIs described the digital solution as too complex. The other half rated the digital platform as rather difficult (16.7%) or acceptable (33.3%). No PI rated the PELICAN@home as user-friendly. From the patients' perspective, a slightly different picture emerges as no one considered the platform to be too complex. Therefore, the digital platform was considered quite complex by and for the patients, but within acceptable standards. Although it was not clear from the survey that using the digital platform caused anxiety in patients, pilot testing of the user-friendliness of implemented digital solutions must be considered in future trials.Four primary reasons for the slow recruitment rate were identified in the qualitative study as follows:Topical treatment of LNP is underutilized in clinical practice. This should be viewed against the background of less attention paid to the application of less invasive pharmacological versus the more invasive treatment options within the pain center.Referral of patients suffering from LNP (and pain conditions in general) from primary care to multidisciplinary pain centers is slow and often occurs only after other specialties have been repeatedly consulted. Acute or subacute pain syndromes are rarely observed in tertiary pain centers. Therefore, future studies in this field should be firmly anchored with primary care to enroll these patients on time.Some study protocol-related criteria negatively impacted recruitment (e.g., a ban on the previous use of gabapentinoids).Finally, some pain patients, as well as caregivers, proved to be less digitally savvy than expected, so a paper backup system had to be provided.