The Chronic Overlapping Pain Condition Screener

The identification of the expert panels for each COPC was undertaken by authors DAW and WM on the basis of published research, extramural funding, and contributions to existing diagnostic criteria as described in Schrepf, et al. 2020. Each of the thirty experts (i.e., 3 per COPC) was contacted individually to describe the purpose and scope of the project. Upon agreement to participate, experts were provided with the published diagnostic criteria for their COPC, asked to suggest any additional criteria, and asked to convert the criteria to a patient self-report format if it was not already in that format. Additionally, the experts were asked to identify “trigger items” and possible pain reference regions on a body map that could be used to determine if the full criteria should be administered. Working group calls were then conducted with each of the ten condition-specific expert panels, with the goal of reaching consensus regarding the selected criteria, any modifications to the criteria, and associated trigger items. Experts were also asked to provide ICD-10 codes relevant to their COPC, the subject of a previous publication. 21 In some cases, the experts reached consensus during the initial call while in other cases consensus required iterative meetings and emails. The experts were informed before initiating the process that patient focus groups would be convened to assess usability and comprehension (Project two) and validation studies conducted with patients known to have each COPC (Project three). The COPC-S was initially programmed into a working digital prototype via a joint effort involving the authors and Research Triangle Institute. This version of the COPC-S was reviewed by the expert panel with subsequent modifications to some modules. It also underwent reliability testing using multiple standardized sets of mock patients with known combinations of COPCs to ensure triggering items and diagnostic criteria produced the intended final report. This working prototype was then programmed into the REDCap environment at Michigan Medicine. REDCap was chosen because it is freely available to non-profit institutions that join the REDCap consortium, ensuring access for the vast-majority of NIH-funded researchers. In order to assess usability and comprehension, patient stakeholders were recruited from the Back and Pain Center Research Patient Advisory Committee, a resource within the University of Michigan Back and Pain Center composed of patients with chronic pain who have indicated a desire to help improve research and provider interactions by providing structured feedback. A total of thirteen patients were selected to take part in one of two hour-long web-based focus groups. The Michigan Medicine Institutional Review Board approved all projects in the study with an exempt determination as research that, “only includes interactions involving educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior (including visual or auditory recording).” All participants provided written informed consent through the Institutional Review Board for Michigan Medicine. Primary points of emphasis for the focus groups were (1) whether the instructions were clear and understandable, (2) if they understood what was being asked in each section of the COPC-S, (3) whether the response options were sufficient and understandable, and (4) whether any other aspect of the COPC-S was difficult to understand or use. Follow-up questions were asked about any noted difficulties so that comprehension and usability could be improved prior to the validation study. Following completion of the focus groups, minor adjustments were made to the COPC-S REDCap environment, primarily relating to color scheme (i.e., having the body map accessible to color-blind individuals), and more clearly formatting the question responses within the display. Ideally, the COPC-S would provide screening classifications that agree with those obtained by a physician administering published criteria as would occur in a clinical setting. Thirty individuals were recruited from the Back and Pain Center at Michigan Medicine, with a minimum of three patients having a known diagnosis for each COPC. All participants provided written informed consent through the Institutional Review Board for Michigan Medicine, and the study was approved as exempt as described under Project Two. Patients could have more than one COPC diagnosis. Two physicians, one male, and one female, administered the unmodified published versions of the ten COPC criteria displayed in Table 2 to each of the thirty patients via secure internet connection. The patients also completed the COPC-S. The order of administration of interview and COPC-S was counter-balanced by randomization. The administration of both diagnostic assessments occurred within no fewer than seven days and no more than fourteen days of each other. Thus, a total of 300 screening classifications (i.e., 30 patients x 10 diagnoses) could be compared between the two methods. The COPC-S screening classifications and those obtained from the physicians were then compared, for each COPC in turn as well as for global presence of a COPC, using the Cohen’s Kappa statistic. See Table 2 . For each COPC, the statistical convention indicating “substantial agreement” (≥ .61) was reached, and overall agreement was strong. 26 A review of discrepancies between the classifications obtained by each approach found that most discrepancies were internal to the same patient answering an identical question with different responses, rather than problems with the self-report format, triggering functions, or program logic. Furthermore, discrepancies did not appear to result from the order of administration of the physician interview and COPC-S. The COPC-S is available with licensing agreement at: https://copcscreener.com/

The COPC-S is an efficient tool for screening ten common and debilitating pain conditions. The COPC-S can be administered online and has been made widely available to researchers and clinicians. Patient focus groups were used to improve the comprehensibility and usability of the COPC-S, and a small cohort of patients provided preliminary evidence that the COPC-S largely agrees with diagnostic classifications obtained by a physician’s clinical interview using published research or diagnostic criteria. The COPC-S relies upon research classification criteria and therefore was not designed to replace a physician’s diagnosis. However, it does provide an efficient method for assessing all ten COPCs within a roughly five to fifteen minute time-frame and can be completed at home. Such knowledge could inform subsequent diagnostic work and/or help to guide more informed clinical care. Further, the use of the COPC-S broadly within pain research studies of targeted conditions would provide important parallel data. Multiple studies have shown that the number of COPCs assessed via patient self-report research criteria is associated with relevant study outcomes. As examples, the number of COPCs present in an individual in the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) study was associated with greater pain intensity, interference, missed days of activity, and the presence of high-impact pain. 17 In a parallel publication, similar effects were shown for psychological variables like symptoms of depression and post-traumatic stress disorder. 5 In another parallel publication, the number of COPCs in a given individual was strongly associated with worse jaw pain, neck pain, and orofacial limitations, 24 indicating that other pain conditions affect condition-specific measures. These findings suggest that the number of COPCs in a given individual provides important clinical information that extends beyond an understanding of the presenting pain diagnosis. Data from other studies examining one versus many COPCs have identified differences in brain chemistry, structure, and function, immune function, and psychophysical responses between patients with a single, anatomically-focused chronic pain issue and those with multiple chronic pain issues. 6 , 9 A recent paper using UK BIOBANK data identified genetic polymorphisms that differ between these groups and associated structural implications in the central nervous system such as impaired axonogenesis in subcortical brain regions. 10 These findings strongly suggest that commonly used treatments targeting specific peripheral structures are unlikely to be optimally effective in patients with multiple COPCs. Therefore, the COPC-S may be useful for enriching clinical trials and may provide a novel focus in observational studies where assessment of COPCs would previously have been deemed too burdensome.

In 2011, the Institute of Medicine released a seminal report, Relieving Pain in America, that identified critical areas of further research needed to make headway against the great challenge presented by chronic pain in the United States. 1 Chronic Overlapping Pain Conditions (COPCs) figured prominently in the report as COPCs collectively impact millions of Americans, occur in individuals who account for nearly half of chronic pain cases, and consume billions of healthcare dollars annually. 14 , 25 COPCs refer to a set of painful conditions that show higher levels of co-occurrence in the general population than expected by individual disease prevalence. Moreover, COPCs are heterogenous, with some individuals experiencing pain in that is anatomically localized, and others experiencing pain multiple body regions. Ten conditions are currently recognized as COPCs; they include vulvodynia (VVD), temporomandibular disorders (TMD), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), irritable bowel syndrome (IBS), urologic chronic pelvic pain syndromes (UCPPS), fibromyalgia (FM), painful endometriosis (pENDO), chronic tension-type headache (TTH), chronic migraine headache (MI), and chronic low back pain (cLBP). Administrative database research using validated ICD-10 codes from a large midwestern medical system indicated that these ten COPCs tend to co-occur in any combination at rates higher than those seen for other important, whether painful or non-painful, chronic conditions such as diabetic neuropathy and chronic obstructive pulmonary disease. 21 This electronic health record study of all ten COPCs broadly agrees with many smaller studies demonstrating co-occurrences within smaller subsets of these ten COPCs (e.g., IBS and migraine). 12 In fact, while each of these ten conditions can occur by itself, a localized pain presentation of any of these conditions appears to represent a minority of cases when examined in large scale studies of COPCs such as those looking at UCPPS and TMD. 11 , 23 Recent work suggests that greater numbers of COPCs are associated with underlying neurobiological vulnerabilities that may promote pain including impaired axonogenesis in brain structures, 10 psychological factors such as high levels of somatic symptoms and sensory sensitivity, 5 , 22 and environmental factors such as early life deprivation and abuse. 4 . Furthermore, health-care utilization increases with each additional COPC. 4 Put simply, addressing the appearance, persistence, and burden of chronic pain requires a deeper understanding of COPCs. Efforts by clinicians and researchers to evaluate COPCs have long been hampered by a lack of resources to comprehensively assess even a few painful conditions within the same individual. Comprehensive assessment of ten or more painful conditions is difficult to even envision. Assessment usually occurs in a specialty clinic where the focus is likely to be on just one of the COPCs most closely aligned to the physician’s training (e.g., a dentist may assess for TMD but may not attend to the bladder pain that would be recognized by a urologist). Needed is a simple and efficient tool to screen for COPCs in any clinical or research setting so that the neurobiological, psychological, environmental, and social correlates of COPCs can be better understood. Here we present such a tool, the Chronic Overlapping Pain Condition-Screener (COPC-S). Three phases of this project are described. In the first, a panel with expertise in the diagnostic criteria for each COPC was convened to select, and in some cases, convert existing criteria into a self-report format. The expert panel also identified decision rules for each COPC that would “trigger” the administration of each COPC module (described subsequently). All decisions were made by consensus. In the second phase, the COPC-S was programmed into the Research Electronic Data Capture (REDCap) environment, 8 and patient focus groups representing each of the COPCs were conducted to evaluate ease of use and comprehension. In the final phase, a validation study was undertaken wherein patients representing each of the COPCs were administered both (a) the published diagnostic criteria for each of the ten COPCs by a physician interview and (b) the COPC-S in order to assess agreement between the two methods. We find that the COPC-S performed well for its intended purpose as a research or clinical screening tool.