# Exclusion criteria in clinical trials of treatments for neuropathic pain: a systematic analysis

## TL;DR

This study shows that clinical trials for neuropathic pain often use strict exclusion criteria, which may limit how well their results apply to real-world patients.

## Contribution

The study systematically analyzes the prevalence and impact of exclusion criteria in neuropathic pain trials, highlighting gaps in reporting and generalizability.

## Key findings

- Medical comorbidities, age restrictions, and pain score requirements were the most common exclusion criteria.
- Psychological comorbidities were excluded in over half of trials, despite their prevalence in chronic pain patients.
- Only a minority of trials reported key patient flow metrics, limiting transparency and generalizability.

## Abstract

Clinical trials for neuropathic pain often employ strict exclusion criteria that may limit the generalizability of their findings to real-world clinical populations. This study systematically analyzed the nature, prevalence, and reporting quality of exclusion criteria in neuropathic pain trials.

We conducted a systematic review of studies published from 2012 to 2022 to analyze exclusion criteria from clinical trials studying treatments for neuropathic pain. We extracted data on the number, type, and frequency of exclusion criteria used. We also analyzed patient flow metrics, including screening, eligibility, enrollment, and completion rates, identified key missing information, and performed correlations between different exclusion criteria to establish patterns in exclusion criteria use.

We included 161primary clinical trial publications of neuropathic pain interventions in our analysis. Most trials examined medication-based interventions and were placebo/sham controlled. The median number of exclusion criteria per study was 5 (IQR 4–7)). Medical comorbidities (86.4%), age restrictions (71.0%), and minimum pain score requirements (71.6%) were used most often as exclusion criteria. Psychological comorbidities were excluded in 56.8% of trials, despite being common in chronic pain populations. Only 36.4% of trials reported the number of patients screened, and 43.8% reported eligibility numbers, highlighting significant gaps in transparent reporting. Among trials that did report patient flow metrics, the mean eligibility rate was 67.9% of screened patients, while the mean enrollment rate was 60.9% of screened patients. We observed moderate correlations between certain exclusion criteria, particularly between minimum pain duration and score requirements (r = 0.56), and weak correlation between the presence of other painful conditions and patients on other treatments (r = 0.40).

Our findings demonstrate that neuropathic pain trials frequently employ multiple exclusion criteria that may significantly limit their generalizability to clinical practice. The high prevalence of psychological comorbidity exclusions is particularly concerning given their common co-occurrence with chronic pain. Additionally, inconsistent reporting of patient flow metrics hampers the assessment of how exclusion criteria affect trial recruitment and generalizability. We recommend standardization of exclusion criteria reporting and careful consideration of whether strict exclusions truly serve trial objectives.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42023387885, identifier CRD42023387885.