Association between systemic medication use and severity of dry eye signs and symptoms in the DRy eye assessment and management (DREAM) study.

PURPOSE: Some systemic medications are reported to be associated with dry eye disease (DED), yet their associations with the severity of DED signs and symptoms are not well studied. To evaluate these associations, we performed a secondary analysis of data from the DRy Eye Assessment and Management (DREAM) Study. METHODS: Participants (N = 535) were assessed for DED signs using tear break-up time (TBUT), Schirmer testing, corneal fluorescein staining, conjunctival lissamine green staining, meibomian gland dysfunction (MGD), and tear osmolarity and DED symptoms using the Ocular Surface Disease Index (OSDI). We derived a composite signs severity score from the 6 DED signs and categorized participant-reported systemic medications into antidepressants, antihistamines, aspirin, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs, proton pump inhibitors, statins, vitamin D3, and medications for diabetes mellitus, hypertension, hypothyroidism, migraine, and seizure. Generalized linear models were used to compare DED symptom and sign scores between medication users and non-users, with adjustment for factors associated with DED severity. RESULTS: Compared to non-users, antihistamine users had lower TBUT (p = 0.01) and higher OSDI score (p = 0.02); aspirin users had lower TBUT (p = 0.02); corticosteroid users had lower TBUT (p = 0.02), lower Schirmer test scores (p = 0.03), higher cornea fluorescein staining (p = 0.01), higher composite severity score (p = 0.01), and higher OSDI score (p = 0.03); seizure medication users had higher composite severity score (p = 0.02); vitamin D3 users had lower TBUT (p = 0.001) and greater MGD (p = 0.03); and diuretic users had less MGD (p = 0.03). CONCLUSIONS: Certain systemic medications may be associated with more severe DED. This may guide prescription practices in patients with DED.

Ecological momentary assessment of pelvic pain and urinary urgency variability in urologic chronic pelvic pain syndrome and their association with illness impact and quality of life: Findings from the multidisciplinary approach to the study of chronic pelvic pain symptom patterns study.

PURPOSE: This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM). MATERIALS AND METHODS: A previously validated smart phone app (M-app) was provided to willing Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) participants. M-app notifications were sent 4-times daily for 14 days inquiring about PP and UU severity. A clustering algorithm that accounted for variance placed participants into PP and UU variability? clusters. Associations between clusters and QOL and IIM were then determined. RESULTS: A total of 204 participants enrolled in the M-app study (64% female). M-app compliance was high (median 63% of surveys). Cluster analysis revealed k = 3 (high, low, none) PP clusters and k = 2 (high, low) UU clusters. When adjusting for baseline pain severity, high PP variability, but not UU variability, was strongly associated with QOL and IIM; specifically worse mood, worse sleep and higher anxiety. UU and PP clusters were associated with each other (p < 0.0001), but a large percentage (33%) of patients with high PP variability had low UU variability. CONCLUSIONS: PP variability is an independent predictor of worse QOL and more severe IIM in UCPPS participants after controlling for baseline pain severity and UU. These findings suggest alternative pain indices, such as pain variability and unpredictability, may be useful adjuncts to traditional measures of worst and average pain when assessing UCPPS treatment responses.

Benefit-risk assessment and reporting in clinical trials of chronic pain treatments: IMMPACT recommendations.

ABSTRACT: Chronic pain clinical trials have historically assessed benefit and risk outcomes separately. However, a growing body of research suggests that a composite metric that accounts for benefit and risk in relation to each other can provide valuable insights into the effects of different treatments. Researchers and regulators have developed a variety of benefit-risk composite metrics, although the extent to which these methods apply to randomized clinical trials (RCTs) of chronic pain has not been evaluated in the published literature. This article was motivated by an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting and is based on the expert opinion of those who attended. In addition, a review of the benefit-risk assessment tools used in published chronic pain RCTs or highlighted by key professional organizations (ie, Cochrane, European Medicines Agency, Outcome Measures in Rheumatology, and U.S. Food and Drug Administration) was completed. Overall, the review found that benefit-risk metrics are not commonly used in RCTs of chronic pain despite the availability of published methods. A primary recommendation is that composite metrics of benefit-risk should be combined at the level of the individual patient, when possible, in addition to the benefit-risk assessment at the treatment group level. Both levels of analysis (individual and group) can provide valuable insights into the relationship between benefits and risks associated with specific treatments across different patient subpopulations. The systematic assessment of benefit-risk in clinical trials has the potential to enhance the clinical meaningfulness of RCT results.

Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations.

ABSTRACT: Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.

Ocular Discomfort and Quality of Life Among Patients in the Dry Eye Assessment and Management Study.

PURPOSE: To assess the association of severity of ocular discomfort with measures of quality of life among patients with moderate to severe dry eye disease (DED). METHODS: This is a prospective, observational, cohort study within a randomized clinical trial. Patients (N = 535) in the Dry Eye Assessment and Management study with moderate to severe DED completed the Ocular Surface Disease Index on DED symptoms, the SF-36 on quality of life, and the Brief Ocular Discomfort Inventory questionnaire and had a comprehensive ophthalmic assessment by a study-certified clinician. The ocular discomfort on average over the past week was scored on an 11-point scale (0 for no discomfort and 10 for discomfort as bad as you can imagine). RESULTS: The average ocular discomfort scores for patients ranged from 0 to 10, with a mean of 4.28. Discomfort scores did not vary with demographic characteristics, signs of DED, self-reported depression, or self-reported nonocular pain conditions. Ocular discomfort scores did correlate moderately to strongly with total Ocular Surface Disease Index scores (Spearman correlation coefficient, rs, 0.47-0.67) and with measures of interference with activities of daily living [general activity level, mood, walking ability, ability for normal work, relations with other people, sleep, and enjoyment of life (rs = 0.39-0.65)]. CONCLUSIONS: Among patients in the Dry Eye Assessment and Management study, worse ocular discomfort was associated with worse overall DED symptoms and interfered to a greater degree with activities of daily living. Ocular discomfort is an important part of the assessment of patients with DED.

Quantitative assessment of nonpelvic pressure pain sensitivity in urologic chronic pelvic pain syndrome: a MAPP Research Network study.

Experimental pain sensitivity was assessed in individuals with urologic chronic pelvic pain syndrome (UCPPS) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. A series of computer-controlled pressure stimuli were delivered to the thumbnail bed, an asymptomatic site distant from the area of UCPPS pain that is considered to be indicative of overall body pain threshold. Stimuli were rated according to a standardized magnitude estimation protocol. Pain sensitivity in participants with UCPPS was compared with healthy controls and a mixed pain group composed of individuals with other chronic overlapping pain conditions, including fibromyalgia, chronic fatigue, and irritable bowel syndromes. Data from 6 participating MAPP testing sites were pooled for analysis. Participants with UCPPS (n = 153) exhibited an intermediate pain sensitivity phenotype: they were less sensitive relative to the mixed pain group (n = 35) but significantly more sensitive than healthy controls (n = 100). Increased pain sensitivity in patients with UCPPS was associated with both higher levels of clinical pain severity and more painful body areas outside the pelvic region. Exploratory analyses in participants with UCPPS revealed that pain sensitivity increased during periods of urologic symptom flare and that less pressure pain sensitivity at baseline was associated with a greater likelihood of subsequent genitourinary pain improvement 1 year later. The finding that individuals with UCPPS demonstrate nonpelvic pain hypersensitivity that is related to clinical symptoms suggests that central nervous system mechanisms of pain amplification contribute to UCPPS.

Assessment of Gender-Based Linguistic Differences in Physician Trainee Evaluations of Medical Faculty Using Automated Text Mining.

Importance: Women are underrepresented at higher ranks in academic medicine. However, the factors contributing to this disparity have not been fully elucidated. Implicit bias and unconscious mental attitudes toward a person or group may be factors. Although academic medical centers use physician trainee evaluations of faculty to inform promotion decisions, little is known about gender bias in these evaluations. To date, no studies have examined narrative evaluations of medical faculty by physician trainees for differences based on gender. Objective: To characterize gender-associated linguistic differences in narrative evaluations of medical faculty written by physician trainees. Design, Setting, and Participants: This retrospective cohort study included all faculty teaching evaluations completed for the department of medicine faculty by medical students, residents, and fellows at a large academic center in Pennsylvania from July 1, 2015, through June 30, 2016. Data analysis was performed from June 1, 2018, through July 31, 2018. Main Outcomes and Measures: Word use in faculty evaluations was quantified using automated text mining by converting free-text comments into unique 1- and 2-word phrases. Mixed-effects logistic regression analysis was performed to assess associations of faculty gender with frequencies of specific words and phrases present in a physician trainee evaluation. Results: A total of 7326 unique evaluations were collected for 521 faculty (325 men [62.4%] and 196 women [37.6%]). The individual words art (odds ratio [OR], 7.78; 95% CI, 1.01-59.89), trials (OR, 4.43; 95% CI, 1.34-14.69), master (OR, 4.24; 95% CI, 1.69-10.63), and humor (OR, 2.32; 95% CI, 1.44-3.73) were significantly associated with evaluations of male faculty, whereas the words empathetic (OR, 4.34; 95% CI, 1.56-12.07), delight (OR, 4.26; 95% CI, 1.35-13.40), and warm (OR, 3.45; 95% CI, 1.83-6.49) were significantly associated with evaluations of female faculty. Two-word phrases associated with male faculty evaluations included run rounds (OR, 7.78; 95% CI, 1.01-59.84), big picture (OR, 7.15; 95% CI, 1.68-30.42), and master clinician (OR, 4.02; 95% CI, 1.21-13.36), whereas evaluations of female faculty were more likely to be associated with model physician (OR, 7.75; 95% CI, 1.70-35.39), just right (OR, 6.97; 95% CI, 1.51-32.30), and attention (to) detail (OR, 4.26; 95% CI, 1.36-13.40). Conclusions and Relevance: The data showed quantifiable linguistic differences between free-text comments about male and female faculty in physician trainee evaluations. Further evaluation of these differences, particularly in association with ongoing gender disparities in faculty promotion and retention, may be warranted.

Psychometric properties of the Canine Symptom Assessment Scale, a multidimensional owner-reported questionnaire instrument for assessment of physical symptoms in dogs with solid tumors.

OBJECTIVE To describe development and initial psychometric testing of the Canine Symptom Assessment Scale (CSAS), a multidimensional owner-reported questionnaire instrument, in a population of dogs with solid tumors enrolled in clinical trials. DESIGN Questionnaire development and validation study. ANIMALS 238 client-owned dogs with solid tumors. PROCEDURES A 14-symptom questionnaire was developed. Symptoms were defined as subjective physical disturbances dogs experienced during the course of daily living as assessed through proxy reports of pet owners. For each symptom, owners reported frequency and severity of the symptom and extent of distress caused by the symptom for the dog and the owner. Questionnaire content, symptom prevalence and dimensionality, internal consistency, and factor structure were examined. Construct and criterion validity were examined via comparison with the Canine Brief Pain Inventory (CBPI). RESULTS Symptom prevalence was high, with pain and lack of energy reported in most dogs. Severity, versus frequency, was most highly correlated with both dog and owner distress. Two symptoms were removed from consideration because of poor performance. Analysis of the remaining 12 symptoms revealed that they could be grouped into 3 factors: malaise, anxiety, and digestive upset. The CSAS factor and total scores demonstrated predictable relationships with quality of life and pain scores as measured by the CBPI, including a significant association between increasing symptom burden and decreasing quality of life. The Cronbach α for the CSAS was 0.77. CONCLUSIONS AND CLINICAL RELEVANCE The 12-item CSAS was a psychometrically sound owner-reported instrument for assessment of symptom frequency and characteristics in client-owned dogs with solid tumors. Potential applications include clinical research and practice settings.

Assessment of physical function and participation in chronic pain clinical trials: IMMPACT/OMERACT recommendations.

Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.

Experimental comparison of parametric versus nonparametric analyses of data from the cold pressor test.

UNLABELLED: Parametric statistical methods are common in human pain research. They require normally distributed data, but this assumption is rarely tested. The current study analyzes the appropriateness of parametric testing for outcomes from the cold pressor test (CPT), a common human experimental pain test. We systematically reviewed published CPT studies to quantify how often researchers test for normality and how often they use parametric versus nonparametric tests. We then measured the normality of CPT data from 7 independent small to medium cohorts and 1 study of >10,000 subjects. We then examined the ability of 2 common mathematical transformations to normalize our skewed data sets. Lastly, we performed Monte Carlo simulations on a representative data set to compare the statistical power of the parametric t-test versus the nonparametric Wilcoxon Mann-Whitney test. We found that only 39% of published CPT studies (47/122) mentioned checking data distribution, yet 72% (88/122) used parametric statistics. Furthermore, among our 8 data sets, CPT outcomes were virtually always nonnormally distributed, and mathematical transformations were largely ineffective in normalizing them. The simulations demonstrated that the nonparametric Wilcoxon Mann-Whitney test had greater statistical power than the parametric t-test for all scenarios tested: For small effect sizes, the Wilcoxon Mann-Whitney test had up to 300% more power. PERSPECTIVE: These results demonstrate that parametric analyses of CPT data are routine but incorrect and that they likely increase the chances of failing to detect significant between-group differences. They suggest that nonparametric analyses become standard for CPT studies and that assumptions of normality be routinely tested for other types of pain outcomes as well.

Core outcome measures for opioid abuse liability laboratory assessment studies in humans: IMMPACT recommendations.

A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting. Although many of the recommended measures are appropriate for assessing the AL of medications from other drug classes, the focus here is on opioid medications because they present unique risks from both physiological (e.g., respiratory depression, physical dependence) and public health (e.g., individuals in pain) perspectives. A brief historical perspective on AL testing is provided, and those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are then discussed. These outcome measures include the following: subjective effects (some of which comprise the primary outcome measures, including drug liking; physiological responses; drug self-administration behavior; and cognitive and psychomotor performance. Before presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.

Expert conference on cancer pain assessment and classification--the need for international consensus: working proposals on international standards.

An increasing number of cancer patients live longer, and palliative care has become an important part of their treatment. Symptoms are often inadequately assessed and managed. A significant challenge in clinical trials is to control for the variability of the samples being studied. To overcome this problem, classification systems have been developed in order to characterise and stratify patients by grouping them according to major common characteristics. The lack of agreed methods for the assessment and classification of cancer pain has been clearly indicated in clinical trials and in clinical practice and may be one possible explanation for the inadequate treatment of cancer pain. This was the background to an international expert meeting arranged in September 2009 in Milan, Italy. The primary aims were to produce recommendations on how to assess and classify cancer pain and to recommend a strategy for the further development, validation and implementation of an international cancer pain classification and assessment system. The recommendations consisted of two basic working proposals, nine specific working proposals and seven recommendations for the further development of a cancer pain classification system. Examples of specific working proposals were to include pain intensity, pain mechanism, breakthrough pain and psychological distress as the core domains in this classification of cancer pain and to measure pain intensity with a 0-10 numerical rating scale with 'no pain' and 'pain as bad as you can imagine' as anchors. The proposed name for this international standard is Cancer Pain Assessment and Classification System (CPACS).

Assessment of cancer-related neuropathy and neuropathic pain.

Cancer-related neuropathic pain syndromes are common and serious complications of a patient's primary malignancy or its treatment, whether by surgery, radiation, or chemotherapy. They may compromise the patient's quality of life as well as their ability to receive effective treatment. In many patients, there may be more than one coexistent neuropathic pain syndrome, posing a diagnostic dilemma that, if unresolved, may result in the institution of therapies that are of limited scope or not targeted at the primary underlying pathophysiology. There is no single adequate diagnostic method that has been established to reliably diagnose or follow patients with cancer-related neuropathic pain syndromes. Clinical assessment of cancer-related neuropathic pain poses some important challenges diagnostically as well as in defining a clear and reliable endpoint assessment in controlled clinical trials. Many different approaches have been applied to the development of assessment or diagnostic tools. Careful review of these methods has been helpful in developing a clearer vision for the future design and refinement of more reliable tools, and more importantly, validation of the clinical utility as well as the reliability of such tools when employed as endpoints in clinical trials focused on prevention, mitigation, or treatment of cancer neuropathic pain.

Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations. Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials.

The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity. To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.

The influence of race and socioeconomic factors on patient acceptance of perioperative epidural analgesia.

BACKGROUND: Ethnic minorities and patients of lower socioeconomic status may be more averse to the acceptance of epidural analgesia than nonminority counterparts and those of higher socioeconomic status, despite evidence for substantial benefit to the patient. METHODS: A scripted telephone survey was developed from the 2000 United States Census by a panel of experts. Contact was attempted at least twice for all patients listed for surgery at the Hospital of the University of Pennsylvania over a 4-mo period. RESULTS: Three thousand seven hundred thirty-nine patients were called and 1265 subjects were successfully contacted and 1193 consented, whereas 72 refused to participate. Seven hundred sixty-two subjects (64%) would accept an epidural if recommended by an anesthesiologist and 425 (36%) would refuse. If the epidural was recommended by both the anesthesiologist and surgeon acceptance increased to 932 (78.5%). The univariate predictor of refusal of perioperative epidural analgesia was African American race. Univariate predictors of acceptance include full- or part-time employment, total household income >$50,001/yr, college graduate, prior epidural treatment, and knowledge of what an epidural is. When the potential confounders of race, total household income, employment, and education were included in a multivariate logistic regression model, African American race predicted refusal (odds ratio [OR], 0.58; P < 0.006; confidence interval [CI], 0.41-0.81) and was the only factor that predicted refusal or acceptance of epidural analgesia. CONCLUSIONS: Acceptance of perioperative epidural analgesia is strongly affected by race and socioeconomic status. Anesthesiologists need to recognize this potential barrier when trying to maximize patient comfort and outcome.

Economic evaluation of oral treatments for neuropathic pain.

UNLABELLED: The effectiveness of amitriptyline, carbamazepine, gabapentin, and tramadol for the treatment of neuropathic pain has been demonstrated, but it is unknown which one is the most cost-effective. We designed a cost-utility analysis of a hypothetical cohort with neuropathic pain of postherpetic or diabetic origin. The perspective of the economic evaluation was that of a third-party payor. For effectiveness and safety estimates, we performed a systematic review of the literature. For direct cost estimates, we used average wholesale prices, and the American Medicare and Clinical Laboratory Fee Schedules. For utilities of health states, we used the Health Utilities Index. We modeled 1 month of therapy. For comparisons among treatments, we estimated incremental cost per utility gained. To allow for uncertainty from variations in drug effectiveness, safety, and amount of medication needed, we conducted a probabilistic Monte Carlo simulation. Amitriptyline was the cheapest strategy, followed by carbamazepine, and both were equally beneficial. Gabapentin was the most expensive as well as the least beneficial. A multivariable probabilistic simulation produced similar results to the base-case scenario. In summary, amitriptyline and carbamazepine are more cost-effective than tramadol and gabapentin and should be considered as first-line treatment for neuropathic pain in patients free of renal or cardiovascular disease. PERSPECTIVE: Prescription practices should be based on the best available evidence, which includes the evaluation of the medication's cost-effectiveness. This does not mean that the cheapest or the most expensive, but rather the most cost-effective medication should be chosen-the one whose benefits are worth the harms and costs. We report a cost-effectiveness evaluation of treatments for neuropathic pain.

Optimal matching with a variable number of controls vs. a fixed number of controls for a cohort study. trade-offs.

Matching is used to control for imbalances between groups, but the preferable strategy for matching is not always clear. We sought to compare two algorithms-optimal matching with a fixed number of controls (OMFC), and optimal matching with a variable number of controls (OMVC). We compared the degree of bias reduction and relative precision using Monte Carlo simulations. We systematically changed the magnitude of the matching variable difference, the variance ratios of the matching variable in the exposed and unexposed groups, the sample size, and the number of unexposed subjects available for matching. OMVC always produced larger removal of bias than the OMFC. The mean percentage reduction of bias was 38.3 with the OMFC and 52.6 with OMVC. OMVC increased the variance 6%. OMVC should be employed when researchers have access to a pool of unexposed subjects because it removes more bias with little loss in precision.