ABSTRACT: Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required. Trials aligned with routine practice pose several challenges, such as determining and enrolling appropriate study participants, deciding on the appropriate level of flexibility in treatment delivery, integrating information on concomitant treatments and adherence, and choosing comparator conditions and outcome measures. Ensuring data quality in real-world clinical settings is another challenging goal. Furthermore, current trials in the field would benefit from analysis methods that allow for a differentiated understanding of effects across patient subgroups and improved reporting of methods and context, which is required to assess the generalizability of findings. At the same time, a range of novel methodological approaches provide opportunities for enhanced efficiency and relevance of pragmatic trials to stakeholders and clinical decision making. In this study, best-practice considerations for these and other concerns in pragmatic trials of pain treatments are offered and a number of promising solutions discussed. The basis of these recommendations was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks.
OBJECTIVES: There is growing interest in collecting outcome information directly from patients in clinical trials. This study evaluates what patients with rheumatic and musculoskeletal diseases (RMDs) consider important to know about symptomatic side effects they may experience from a new prescription drug. METHODS: Patients with inflammatory arthritis, who had one or more prescribed drugs for their disease for at least 12 months, participated in focus groups and individual interviews. Discussions were analysed using reflexive thematic analysis. RESULTS: We conducted seven focus groups with 34 participants across three continents. We found four overarching and two underpinning themes. The 'impact on life' was connected to participants 'daily life', 'family life', 'work life', and 'social life'. In 'psychological and physical aspects' participants described 'limitation to physical function', 'emotional dysregulation' and 'an overall mental state'. Extra tests, hospital visits and payment for medication were considered a 'time, energy and financial burden' of side effects. Participants explained important measurement issues to be 'severity', 'frequency', and 'duration'. Underpinning these issues, participants evaluated the 'benefit-harm-balance' which includes 'the cumulative burden' of having several side effects and the persistence of side effects over time. CONCLUSIONS: In treatment for RMDs, there seems to be an urgent need for feasible measures of patient-reported bother (impact on life and cumulative burden) from side effects and the benefit-harm-balance. These findings contribute new evidence in support of a target domain-an outcome that represents the patient voice evaluating the symptomatic treatment-related side effects for people with RMDs enrolled in clinical trials.
OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.
Consensus , Outcome Assessment, Health Care , Quality of Life , Rheumatology , Humans , Rheumatology/standards , Rheumatic Diseases
OBJECTIVE: To increase awareness and understanding of the principles of Equity, Diversity, and Inclusivity (EDI) within Outcome Measures in Rheumatology's (OMERACT) members. For this, we aimed to obtain ideas on how to promote and foster these principles within the organization and determine the diversity of the current membership in order to focus future efforts. METHODS: We held a plenary workshop session at OMERACT 2023 with roundtable discussions on barriers and solutions to increased diversity within OMERACT. We conducted an anonymous, web-based survey of members to record characteristics including population group, gender identity, education level, age, and ability. RESULTS: The workshop generated ideas to increase diversity of participants across the themes of building relationships [12 topics], materials and methods [5 topics], and conference-specific [6 topics]. Four hundred and seven people responded to the survey (25 % response rate). The majority of respondents were White (75 %), female (61 %), university-educated (94 %), Christian (42 %), spoke English at home (60 %), aged 35 to 55 years (50 %), and did not report a disability (64 %). CONCLUSION: OMERACT is committed to improving its diversity. Next steps include strategic recruitment of members to the EDI working group, drafting an EDI mission statement centering equity and inclusivity in the organization, and developing guidance for the OMERACT Handbook to help all working groups create actionable plans for promoting EDI principles.
Cultural Diversity , Rheumatology , Humans , Female , Male , Societies, Medical , Adult , Middle Aged , Surveys and Questionnaires
OBJECTIVE: This manuscript highlights the importance of enhancing the uptake of Core Outcome Sets (COS) by building partnerships with Collaborators and addressing their needs in COS development. METHODS AND SETTING: This session was structured as a simulation, resembling a format akin to a classic television game show. The moderator posed a series of questions to eight different Collaborator groups who briefly described the importance of COS within their areas of interest. Previous studies examining the uptake of individual core outcomes revealed disparities in uptake rates. The Identified barriers to the uptake of COS include the lack of recommendations for validated instruments for each domain, insufficient involvement of patients and key Collaborator groups in COS development, and a lack of awareness regarding the existence of COS. CONCLUSIONS: This analysis underscores the need for COS development approaches that prioritize the inclusion of patients and diverse Collaborator groups at every stage. While current studies on COS uptake are limited, future research should explore the broader implementation of COS across diverse disease categories and delve into the factors that hinder or facilitate their uptake such as, the importance of COS developers extending their work to recommending domains with well validated instruments. Embracing patient leadership and multifaceted engagement is essential for advancing the relevance and impact of COS in clinical research.
Outcome Assessment, Health Care , Humans , Cooperative Behavior , Rheumatology , Congresses as Topic
Objective: The global impact of osteoarthritis is growing. Currently no disease modifying osteoarthritis drugs/therapies exist, increasing the need for preventative strategies. Knee injuries have a high prevalence, distinct onset, and strong independent association with post-traumatic osteoarthritis (PTOA). Numerous groups are embarking upon research that will culminate in clinical trials to assess the effect of interventions to prevent knee PTOA despite challenges and lack of consensus about trial design in this population. Our objectives were to improve awareness of knee PTOA prevention trial design and discuss state-of-the art methods to address the unique opportunities and challenges of these studies. Design: An international interdisciplinary group developed a workshop, hosted at the 2023 Osteoarthritis Research Society International Congress. Here we summarize the workshop content and outputs, with the goal of moving the field of PTOA prevention trial design forward. Results: Workshop highlights included discussions about target population (considering risk, homogeneity, and possibility of modifying osteoarthritis outcome); target treatment (considering delivery, timing, feasibility and effectiveness); comparators (usual care, placebo), and primary symptomatic outcomes considering surrogates and the importance of knee function and symptoms other than pain to this population. Conclusions: Opportunities to test multimodal PTOA prevention interventions across preclinical models and clinical trials exist. As improving symptomatic outcomes aligns with patient and regulator priorities, co-primary symptomatic (single or aggregate/multidimensional outcome considering function and symptoms beyond pain) and structural/physiological outcomes may be appropriate for these trials. To ensure PTOA prevention trials are relevant and acceptable to all stakeholders, future research should address critical knowledge gaps and challenges.
ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.
Pain , Patient Participation , Humans , Research Design
BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review. OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS. METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators. RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies. CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.
Lupus Erythematosus, Systemic , Rheumatology , Humans , Public Opinion , Outcome Assessment, Health Care , Lupus Erythematosus, Systemic/therapy , Consensus
OBJECTIVE: To investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Multicentre, randomised, controlled, pragmatic strategy trial of higher risk patients with NSTE-ACS, defined by Global Registry of Acute Coronary Events 2.0 score of ≥118, or ≥90 with at least one additional high-risk feature. Participants were randomly assigned to very early IS±revascularisation (<90 min from randomisation) or standard care IS±revascularisation (<72 hours). The primary outcome was a composite of all-cause mortality, new myocardial infarction or hospitalisation for heart failure at 12 months. RESULTS: The trial was discontinued early by the funder due to slow recruitment during the COVID-19 pandemic. 425 patients were randomised, of whom 413 underwent an IS: 204 to very early IS (median time from randomisation: 1.5 hours (IQR: 0.9-2.0)) and 209 to standard care IS (median: 44.0 hours (IQR: 22.9-72.6)). At 12 months, there was no significant difference in the primary outcome between the early IS (5.9%) and standard IS (6.7%) groups (OR 0.93, 95% CI 0.42 to 2.09; p=0.86). The incidence of stroke and major bleeding was similar. The length of hospital stay was reduced with a very early IS (3.9 days (SD 6.5) vs 6.3 days (SD 7.6), p<0.01). CONCLUSIONS: A strategy of very early IS did not improve clinical outcomes compared with a standard care IS in higher risk patients with NSTE-ACS. However, the primary outcome rate was low and the trial was underpowered to detect such a difference. TRIAL REGISTRATION NUMBER: NCT03707314.
Acute Coronary Syndrome , Non-ST Elevated Myocardial Infarction , Percutaneous Coronary Intervention , Humans , Acute Coronary Syndrome/diagnosis , Pandemics , Treatment Outcome , Coronary Angiography , Percutaneous Coronary Intervention/adverse effects
OBJECTIVE: To educate and discuss pain mechanisms (nociceptive, neuropathic, nociplastic) illuminating its possible impact when measuring different outcomes, which may modify, confound and potentially bias the outcome measures applied across various aspects of Rheumatic Musculoskeletal Diseases (RMDs) clinical trials. METHODS: In the plenary presentations, PM lectured on different pain mechanisms and impact on disease activity assessment. Data from two data sets of RMDs patients, which assessed the prevalence and impact of nociplastic pain were presented and reviewed. Audience breakout group sessions and polling were conducted. RESULTS: Mixed pain etiologies may differentially influence disease activity assessment and therapeutic decision-making. Polling demonstrated a consensus on the need to assess different types of pain as a phenotype, as it constitutes an important contextual factor (a variable that is not an outcome of the trial, but needs to be recognized [and measured] to understand the study results), and to standardize across RMDs. CONCLUSION: There is need for a standardized pain measure that can differentiate underlying pain mechanisms.
Chronic Pain , Musculoskeletal Diseases , Rheumatic Diseases , Rheumatology , Humans , Chronic Pain/therapy , Rheumatic Diseases/therapy , Outcome Assessment, Health Care
OBJECTIVES: To develop an understanding of the concept of safety/harms experienced by patients involved in clinical trials for their rheumatic and musculoskeletal diseases (RMDs) and to seek input from the OMERACT community before moving forward to developing or selecting an outcome measurement instrument. METHODS: OMERACT 2023 presented and discussed interview results from 34 patients indicating that up to 171 items might be important for patients' harm-reporting. RESULTS: Domain was defined in detail and supported by qualitative work. Participants in the Special-Interest-Group endorsed (96 %) that enough qualitative data are available to start Delphi survey(s). CONCLUSION: We present a definition of safety/harms that represents the patient voice (i.e., patients' perception of safety) evaluating the symptomatic treatment-related adverse events for people with RMDs enrolled in clinical trials.
Musculoskeletal Diseases , Rheumatology , Humans , Musculoskeletal Diseases/therapy , Outcome Assessment, Health Care , Patient Reported Outcome Measures , Clinical Trials as Topic
OBJECTIVES: The objective of this systematic review was to assess the effects of interleukin-1ß (IL-1ß) inhibitors on gout flares. METHODS: Studies published between 2011 and 2022 that evaluated the effects of IL-1ß inhibitors in adult patients experiencing gout flares were eligible for inclusion. Outcomes including pain, frequency and intensity of gout flares, inflammation, and safety were assessed. Five electronic databases (Pubmed/Medline, Embase, Biosis/Ovid, Web of Science and Cochrane Library) were searched. Two independent reviewers performed study screening, data extraction and risk of bias assessments (Cochrane Risk of Bias Tool 2 for randomised controlled trials [RCTs] and Downs and Black for non-RCTs). Data are reported as a narrative synthesis. RESULTS: Fourteen studies (10 RCTs) met the inclusion criteria, with canakinumab, anakinra, and rilonacept being the three included IL-1ß inhibitors. A total of 4367 patients with a history of gout were included from the 14 studies (N = 3446, RCTs; N = 159, retrospective studies [with a history of gout]; N = 762, post hoc analysis [with a history of gout]). In the RCTs, canakinumab and rilonacept were reported to have a better response compared to an active comparator for resolving pain, while anakinra appeared to be not inferior to an active comparator for resolving pain. Furthermore, canakinumab and rilonacept reduced the frequency of gout flares compared to the comparators. All three medications were mostly well-tolerated compared to their comparators. CONCLUSION: IL-1ß inhibitors may be a beneficial and safe medication for patients experiencing gout flares for whom current standard therapies are unsuitable. REVIEW PROTOCOL REGISTRATION: PROSPERO ID: CRD42021267670.
Arthritis, Gouty , Gout , Adult , Humans , Interleukin Inhibitors , Interleukin-1beta , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Gout/drug therapy , Arthritis, Gouty/drug therapy
Systemic lupus erythematosus (SLE) is a disease of high unmet therapeutic need. The challenge of accurately measuring clinically meaningful responses to treatment has hindered progress towards positive outcomes in SLE trials, impeding the approval of potential new therapies. Current primary end points used in SLE trials are based on legacy disease activity measures that were neither specifically designed for the clinical trial context, nor developed according to contemporary recommendations for clinical outcome assessments (COAs), such as that substantial patient input should be incorporated into their design. The Treatment Response Measure for SLE (TRM-SLE) Taskforce is a global collaboration of SLE clinician-academics, patients and patient representatives, industry partners and regulatory experts, established to realize the goal of developing a new COA for SLE clinical trials. The aim of this project is a novel COA designed specifically to measure treatment effects that are clinically meaningful to patients and clinicians, and intended for implementation in a trial end point that supports regulatory approval of novel therapeutic agents in SLE. This Consensus Statement reports the first outcomes of the TRM-SLE project, including a structured process for TRM-SLE development.
Lupus Erythematosus, Systemic , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Consensus , Outcome Assessment, Health Care
Interrupted time series (ITS) studies are frequently used to examine the impact of population-level interventions or exposures. Systematic reviews with meta-analyses including ITS designs may inform public health and policy decision-making. Re-analysis of ITS may be required for inclusion in meta-analysis. While publications of ITS rarely provide raw data for re-analysis, graphs are often included, from which time series data can be digitally extracted. However, the accuracy of effect estimates calculated from data digitally extracted from ITS graphs is currently unknown. Forty-three ITS with available datasets and time series graphs were included. Time series data from each graph was extracted by four researchers using digital data extraction software. Data extraction errors were analysed. Segmented linear regression models were fitted to the extracted and provided datasets, from which estimates of immediate level and slope change (and associated statistics) were calculated and compared across the datasets. Although there were some data extraction errors of time points, primarily due to complications in the original graphs, they did not translate into important differences in estimates of interruption effects (and associated statistics). Using digital data extraction to obtain data from ITS graphs should be considered in reviews including ITS. Including these studies in meta-analyses, even with slight inaccuracy, is likely to outweigh the loss of information from non-inclusion.
Public Health , Software , Interrupted Time Series Analysis , Time Factors
This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. PURPOSE: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. METHODS: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. RESULTS: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. CONCLUSIONS: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.
Musculoskeletal Diseases , Osteoarthritis , Osteoporosis , Humans , Osteoarthritis/therapy , Musculoskeletal Diseases/therapy , Societies, Medical
ABSTRACT: Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care. This article summarizes methodological considerations for pragmatic trials, mainly concerning methods of fundamental importance to the internal validity of trials. The relationship between these methods and common pragmatic trials methods and goals is considered, recognizing that the resulting trial designs are highly dependent on the specific research question under investigation. The basis of this statement was an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) systematic review of methods and a consensus meeting. The meeting was organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership. The consensus process was informed by expert presentations, panel and consensus discussions, and a preparatory systematic review. In the context of pragmatic trials of pain treatments, we present fundamental considerations for the planning phase of pragmatic trials, including the specification of trial objectives, the selection of adequate designs, and methods to enhance internal validity while maintaining the ability to answer pragmatic research questions.
Analgesics , Pain Management , Humans , Analgesics/therapeutic use , Consensus , Pain/drug therapy , Research Design , Pragmatic Clinical Trials as Topic
OBJECTIVE: To assess the benefits and harms associated with biopsychosocial rehabilitation in patients with inflammatory arthritis and osteoarthritis (OA). METHODS: We performed a systematic review and meta-analysis. Data were collected through electronic searches of Cochrane CENTRAL, MEDLINE, Embase, PsycInfo, and CINAHL databases up to March 2019. Trials examining the effect of biopsychosocial rehabilitation in adults with inflammatory arthritis and/or OA were considered eligible, excluding rehabilitation adjunct to surgery. The primary outcome for benefit was pain and total withdrawals for harm. RESULTS: Of the 27 trials meeting the eligibility criteria, 22 trials (3,750 participants) reported sufficient data to be included in the quantitative synthesis. For patient-reported outcome measures, biopsychosocial rehabilitation was slightly superior to control for pain relief (standardized mean difference [SMD] -0.19 [95% confidence interval (95% CI) -0.31, -0.07]), had a small effect on patient global assessment score (SMD -0.13 [95% CI -0.26, -0.00]), with no apparent effect on health-related quality of life, fatigue, self-reported disability/physical function, mental well-being, and reduction in pain intensity ≥30%. Clinician-measured outcomes displayed a small effect on observed disability/physical function (SMD -0.34 [95% CI -0.57, -0.10]), a large effect on physician global assessment score (SMD -0.72 [95% CI -1.18, -0.26]), and no effect on inflammation. No difference in harms existed in terms of the number of withdrawals, adverse events, or serious adverse events. CONCLUSION: Biopsychosocial rehabilitation produces a significant but clinically small beneficial effect on patient-reported pain among patients with inflammatory arthritis and OA, with no difference in harm. Methodologic weaknesses were observed in the included trials, suggesting low-to-moderate confidence in the estimates of effect.
Osteoarthritis , Quality of Life , Adult , Humans , Randomized Controlled Trials as Topic , Osteoarthritis/diagnosis , Pain
Large variability in the individual response to even the most-efficacious pain treatments is observed clinically, which has led to calls for a more personalized, tailored approach to treating patients with pain (ie, "precision pain medicine"). Precision pain medicine, currently an aspirational goal, would consist of empirically based algorithms that determine the optimal treatments, or treatment combinations, for specific patients (ie, targeting the right treatment, in the right dose, to the right patient, at the right time). Answering this question of "what works for whom" will certainly improve the clinical care of patients with pain. It may also support the success of novel drug development in pain, making it easier to identify novel treatments that work for certain patients and more accurately identify the magnitude of the treatment effect for those subgroups. Significant preliminary work has been done in this area, and analgesic trials are beginning to utilize precision pain medicine approaches such as stratified allocation on the basis of prespecified patient phenotypes using assessment methodologies such as quantitative sensory testing. Current major challenges within the field include: 1) identifying optimal measurement approaches to assessing patient characteristics that are most robustly and consistently predictive of inter-patient variation in specific analgesic treatment outcomes, 2) designing clinical trials that can identify treatment-by-phenotype interactions, and 3) selecting the most promising therapeutics to be tested in this way. This review surveys the current state of precision pain medicine, with a focus on drug treatments (which have been most-studied in a precision pain medicine context). It further presents a set of evidence-based recommendations for accelerating the application of precision pain methods in chronic pain research. PERSPECTIVE: Given the considerable variability in treatment outcomes for chronic pain, progress in precision pain treatment is critical for the field. An array of phenotypes and mechanisms contribute to chronic pain; this review summarizes current knowledge regarding which treatments are most effective for patients with specific biopsychosocial characteristics.
Chronic Pain , Humans , Chronic Pain/psychology , Analgesics/therapeutic use , Pain Management , Phenotype , Pain Measurement/methods
BACKGROUND: In most rheumatic and musculoskeletal diseases (RMDs), global assessments of disease activity by physicians and patients are 'anchor outcomes' in therapeutic trials evaluating whether a treatment is effective. OBJECTIVES: To compare physicians' vs patients' global assessments of disease activity in RMD trials and explore reasons for discrepancies between them. METHODS: Eligible trials were sampled from systematic reviews of treatments for RMDs by using the Cochrane database of systematic reviews (i.e., reviews from the Cochrane Musculoskeletal Group, [CMSG]). Randomized controlled trials (RCTs) of interventions for RMDs were eligible if they reported quantitative analyses of both physicians´ and patients´ global assessments at the same time point for the comparison of the same experimental intervention against the same comparator (i.e., placebo, no treatment, or other treatment). We accepted data from trial comparisons for each type of outcome, regardless of the type of intervention and type of RMD within the CMSG. Using mixed-effects meta-regression models, we assigned the dependent variable as the ratio of odds ratios (ROR) of global change with the experimental intervention, versus the control comparator. An ROR>1 would indicate that physicians rated the experimental intervention more favorable than their patients did. RESULTS: We were able to estimate the ROR (data from both physicians' and patients' global assessments) across 70 trials (116 randomized comparisons) in 7 diseases (ankylosing spondylitis, fibromyalgia, psoriatic arthritis, osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, and gout). The combined ROR across all effectiveness comparisons were rated significantly in favor of the intervention by physicians: ROR=1.15 CI 95% (1.07 to 1.23). This combined ROR was based on a substantial heterogeneity across comparisons (I2=89.1%). Across all the stratified analyses, the type of the RMD was an informative reason for discrepancies, with a statistically significant ROR in rheumatoid arthritis ROR=1.33, CI 95% (1.13 to 1.56), unlike the ROR in all other conditions (ROR=1.04, CI 95% (0.95-1.14). CONCLUSION: In comparative effectiveness research on rheumatology, physicians' global assessments of disease activity, surprisingly, are more in favor of the experimental interventions than are those of the patients.
Arthritis, Rheumatoid , Physicians , Rheumatology , Arthritis, Rheumatoid/drug therapy , Humans , Odds Ratio , Systematic Reviews as Topic
