{"doi":"10.1093/pm/pnae081","title":"Monitoring and reporting adverse events in pragmatic clinical trials testing nonpharmacological pain management interventions","abstract":"Randomized controlled trials (RCTs) are a critical tool for assessing treatment effects of clinical interventions. RCTs are guided by ethical standards and processes to ensure participant safety and data integrity. Ensuring compliance with these standards is specified by policies, and oversight is typically provided by institutional review boards (IRBs), data safety monitoring boards (DSMBs), and others as specified prospectively in a study monitoring plan. Ensuring participant safety requires monitoring and recording adverse events (AEs) as elements that can be analyzed in the context of study findings. Generally speaking, AEs are unfavorable health-related occurrences in human research participants, irrespective of relatedness to research participation.1 They range from unrelated changes in condition to minor tolerability issues to serious safety concerns.2 Guidance for reporting AEs has long been available through a Consolidated Standards for Reporting Trials (CONSORT) statement, which has been updated recently.2 Despite existing guidance to monitor and report them, AEs are underreported in nonpharmacologic pain trials. Palermo and colleagues reviewed 40 trials in adult participants testing psychological treatments for chronic pain and found that only one quarter of them reported AEs.3 A scoping review of 113 trials assessing manual therapy for neck pain found that only 56% of trials reported the tracking of AEs.4 A 2014 review noted that AE reporting was universally poor in 101 trials published in one of three pain journals,5 in which half did not report their AE collection processes and only one-quarter reported any observed AEs.5 Potential factors contributing to poor reporting include journal-based word limits, lack of emphasis on reporting standards by journal editors and peer reviewers, and biased reporting and interpretation of results.6 Pragmatic clinical trials (PCTs) are increasingly being used to inform clinical and policy decisions. They provide evidence of the effectiveness of pain management interventions when delivered in routine clinical settings,7 and as such they aim to address the widely acknowledged gap between what is observed in efficacy trials and implementation into routine clinical care. PCT designs and methodologies differ significantly from more common explanatory efficacy trials by prioritizing external validity and generalizability of results. Reporting of AEs in PCTs can be critical to understanding the safe use of pain management interventions in routine clinical settings. Unique challenges complicate AE data collection, interpretation, and reporting in PCTs.8 PCTs typically study established interventions, are often delivered by a larger number and diversity of healthcare providers, and have broad eligibility criteria. Thus, PCTs intentionally include participants with multiple health conditions, representative of real-world clinical settings, who may be more likely to experience a wide array and frequency of AEs not directly attributable to a study intervention. Additional factors that can complicate AE relatedness determinations include complexities and the multicomponent nature of many nonpharmacological pain management interventions, lack of a comparison control arm, and reliance upon clinical documentation to identify AEs. Both under- and over-reporting of AEs can potentially lead to additional and unnecessary testing, inappropriately denying enrollment of otherwise eligible individuals in future research, errant safety profiling of nonpharmacological therapies, and/or exposing patients to care presumed to be safe but with risk not appreciated accurately. Authors of this Commentary are members of the Pain Management Collaboratory (PMC). This trial network is conducting 13 PCTs in veteran and military health delivery systems toward closing implementation gaps for the use of nonpharmacological approaches to manage pain and common co-occurring conditions.9 Consistent with emerging literatur","journal":"Pain Medicine","year":2024,"id":472379,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":428365,"name":"Stacey Young‐McCaughan","orcid":"0000-0002-3327-5233","position":1,"is_corresponding":false},{"id":793957,"name":"Alison F. Davis","orcid":"0000-0002-8610-6580","position":2,"is_corresponding":false},{"id":411319,"name":"Robert Vining","orcid":"0000-0003-4672-4613","position":3,"is_corresponding":false},{"id":673561,"name":"Joseph Ali","orcid":"0000-0002-4767-2512","position":4,"is_corresponding":false},{"id":390468,"name":"Julie M. Fritz","orcid":"0000-0002-3599-1057","position":5,"is_corresponding":false},{"id":436206,"name":"Benjamin J. Morasco","orcid":"0009-0003-0106-5105","position":6,"is_corresponding":false},{"id":360893,"name":"Daniel I. Rhon","orcid":"0000-0002-4320-990X","position":7,"is_corresponding":false},{"id":1307879,"name":"Robert Roogow","orcid":null,"position":8,"is_corresponding":false},{"id":688986,"name":"Tassos C. Kyriakides","orcid":"0000-0001-8913-108X","position":9,"is_corresponding":false},{"id":431791,"name":"Robert D. Kerns","orcid":"0000-0002-3834-973X","position":10,"is_corresponding":false},{"id":793956,"name":"Amy Burns","orcid":"0000-0002-9778-7852","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-19T02:05:53.032464Z","pmid":"39514880","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}