Identification of prescription opioid misuse and abuse behaviors and risk factors in chronic pain patients using the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ).

OBJECTIVES: To identify patient risk factors associated with prescription opioid misuse and abuse as well as groupings of misuse and abuse behaviors as measured by the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ). METHODS: Adults with chronic pain requiring long-term treatment with opioids completed the POMAQ and other study questionnaires. Latent class analysis (LCA) was used to examine underlying subgroups exhibiting particular risk profiles. Patient demographic and clinical characteristics were examined as covariates and the concordance between the identified latent classes at-risk classifications and the POMAQ clinical scoring algorithm was assessed. RESULTS: Analysis of data from 809 patients revealed four classes: "chronic pain, low risk" (n = 473, low to no prevalence of POMAQ behaviors), "chronic pain, comorbid condition" (n = 152, high prevalence of anti-anxiety, sleeping pill, and antihistamine use), "at risk" (n = 154, taking more opioids than prescribed and drinking alcohol with opioids more frequently than other groups), and "high risk" (n = 30, highest prevalence of each behavior). The "high risk" group was associated with being younger, less educated, and unemployed compared to other groups. When examining the LCA classes by groups defined by the original POMAQ clinical scoring algorithm, the "high risk" class had the highest proportion of participants identified with abuse behaviors (46.7%), compared to just 4.7% in the "chronic pain, low risk" group. CONCLUSIONS: Findings suggest there are four distinct subgroups of patients defined by chronic opioid misuse and abuse behaviors and support the use of the POMAQ to identify risk factors associated with prescription opioid misuse and abuse.

Clinical scoring algorithm for the prescription opioid misuse and abuse questionnaire (POMAQ).

OBJECTIVE: The Prescription Opioid Misuse and Abuse Questionnaire (POMAQ) was developed to identify prescription opioid misuse and abuse among patients with chronic pain. A clinical scoring algorithm was developed and refined to align with the patient experience. METHODS: This study utilized data from the POMAQ validation study (3033-4, NCT02660606) conducted on a sample of patients with chronic pain living in the United States. The study was carried out in two phases. Two purposefully enriched patient samples, one for each phase, were created based on patient responses to select POMAQ items and the availability of urine and hair samples. Two clinical experts (SHS, SFB) reviewed patient data to classify prescription opioid use behavior. Classification differences were adjudicated by a third clinical expert (JTF). Comparisons were made between the final clinical classification determined by the experts and the proposed classification based on the POMAQ algorithm. RESULTS: Sixty patients were included in Phase I (only POMAQ data) and 52 in Phase II (including POMAQ and ancillary sources [e.g. electronic medical records, urine toxicity screen]). Refinements were made to the POMAQ scoring algorithm following discussions with clinical experts to ensure it was clinically relevant. For both phases, classifications were reviewed and discussed to achieve maximal concordance of classifications across experts. The proposed scoring algorithm was then modified to maximize agreement with the expert interpretation of clinically relevant patient experiences. CONCLUSION: The clinical scoring algorithm for the POMAQ was developed and refined to reflect clinically relevant patient behaviors identified by expert review. Future testing is needed to determine the sensitivity and specificity of this measure.

Patient-reported outcomes predict overall survival in older patients with acute myeloid leukemia.

INTRODUCTION: Patient-reported outcomes (PROs) predict overall survival (OS) in many cancer types, but there is little evidence of their prognostic value in older patients with acute myeloid leukemia (AML). We examined whether the Functional Assessment of Cancer Therapy - Leukemia (FACT-Leu) predicted OS beyond established prognostic factors among these patients. MATERIALS AND METHODS: Data were from AML2002 (n = 309), a randomized phase 2/3 study comparing decitabine plus talacotuzumab versus decitabine alone in older AML patients ineligible for intensive chemotherapy. We used ridge-penalized Cox proportional hazards models to estimate the association between baseline FACT-Leu scales and OS. We then conducted a bootstrap analysis to determine how often FACT-Leu scales appeared in forward- and backward- selected "final models" predicting OS relative to prognosticators from the AML Composite Model (AML-CM; e.g., chronic comorbidities, previous cancer, cytogenetic/molecular risk). RESULTS: In ridge-penalized models, the FACT-Leu Physical Well-Being (PWB), Trial Outcomes Index (TOI), and Total scales predicted OS. Adjusting for AML-CM factors, an important increase (3 points) in PWB score was associated with a 14% reduction in the hazard of death. In the bootstrap analysis, the PWB scale appeared in 93% of backward- and 98% of forward selected models, while the TOI [57% (backward), 79% (forward)] and FACT-Leu Total [51% (backward), 78% (forward)] appeared less often in final models. DISCUSSION AND CONCLUSIONS: These results indicate PROs' value for predicting outcomes among older AML patients and underscore the need to more systematically collect PRO data in routine care with these patients. CLINICALTRIALS: gov Registration: NCT02472145.

Evaluating the Content Validity, Clarity, and Relevance of Two Patient-Reported Outcomes for Use With Adults With EGFR-Mutated NSCLC.

INTRODUCTION: NSCLCs account for most lung cancers; approximately 30% involve a mutation in the EGFR gene. This study sought to identify one or more patient-reported outcome (PRO) measures relevant for use in clinical trials to assess symptoms and health-related quality of life in this population. METHODS: Patients with NSCLC from the United States, Europe, and Asia and including those with an exon 20 insertion mutation and other EGFR mutations participated in a combination of concept elicitation and cognitive debriefing interviews to report symptoms and impacts of their NSCLC and provide feedback on the clarity and relevance of several PRO measures. RESULTS: A total of 30 individuals participated (mean age = 57 years, 87% female, 80% white). The most often reported symptoms included fatigue, shortness of breath, cough, and weight loss. Individuals with the exon 20 insertion mutation (n = 21) more frequently reported negative impacts on daily life, physical functioning, and social functioning but less frequently reported negative impacts to emotional functioning. The PROMIS Short-Form version 2.0-Physical Function 8c and the NSCLC Symptom Assessment Questionnaire were deemed clear, relevant, and easy to complete. The concepts identified during the concept elicitation portion of the interviews were mapped to the content of each PRO, and all items within both PROs were endorsed by at least 20% of the participants. CONCLUSIONS: These results support the content validity, clarity, and relevance of the PROMIS Short-Form version 2.0-Physical Function 8c and the NSCLC Symptom Assessment Questionnaire in a population with EGFR-mutated NSCLC. Both would be appropriate for inclusion in future studies.

Construct validity and reproducibility of the Prescription Opioid Misuse And Abuse Questionnaire (POMAQ).

OBJECTIVE: The Prescription Opioid Misuse and Abuse Questionnaire was developed to identify prescription opioid abuse and misuse among patients with chronic pain, however, evidence of construct validity and reproducibility is needed. METHODS: Chronic pain patients were recruited from five Department of Defense Military Health System clinics across the United States. Construct validity was examined using subjective clinician-reported and patient-reported measures as well as objective information (e.g. hair/urine drug screens and electronic medical records). Test-retest reliability was assessed across 2 timepoints among a subgroup of patients with stable chronic pain. RESULTS: Of 3,263 screened patients, 938 (28.7%) met eligibility and were enrolled; 809 (86.2%) completed the Prescription Opioid Misuse and Abuse Questionnaire. Construct validity was supported by comparison to other validated questionnaires and hair and urine screens which yielded high agreements with patient reports on the Prescription Opioid Misuse and Abuse Questionnaire. Electronic medical record data supported patients' Prescription Opioid Misuse and Abuse Questionnaire responses regarding physician and emergency room visits and opioid refills. The Prescription Opioid Misuse and Abuse Questionnaire had excellent test-retest reliability; the percentage agreement between the two Prescription Opioid Misuse and Abuse Questionnaire administrations was high (>90%) for most questions. DISCUSSION: Results suggest that the Prescription Opioid Misuse and Abuse Questionnaire is a valid and reproducible tool that can be used to assess the presence of prescription opioid misuse and abuse among patients with chronic pain.

Establishing the content validity of the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ) among chronic pain patients.

OBJECTIVES: Content validation is essential in the development of patient-reported instruments to ensure relevancy and understandability. The aim was to evaluate patient understanding of the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ) using cognitive interviewing among adults with chronic moderate to severe pain. METHODS: This qualitative study involved a one-time in-clinic visit to conduct one-on-one cognitive interviews among participants with chronic moderate to severe pain from four groups: (1) Known Opioid Abuse; (2) Known Abuse of Other Substances (e.g. alcohol, benzodiazepines); (3) Opioid Non-abuse; and (4) No Chronic Opioid Use. Patients were recruited from 6 US clinical centers. Concept elicitation questions regarding misuse and abuse were asked at interview start; the POMAQ was completed via a web interface followed by a cognitive interview regarding POMAQ items and response options. RESULTS: 56 patients were enrolled. Mean age was 48.7 ± 12.3 years; 57% female; 80% Caucasian; mean duration of chronic pain was 11.2 ± 8.2 years with lower back pain predominating at 75%. Overall, the POMAQ was well-understood and received positive feedback. A few (n = 6, 11%) expressed concerns about completing the POMAQ using a secure internet site as they either indicated they were not computer savvy (n = 3, 5%) or were concerned about internet security (n = 3, 5%). Minor wording modifications were made to the POMAQ to enhance clarity and understanding of the POMAQ. CONCLUSIONS: The POMAQ demonstrated content validity among patients with moderate to severe chronic pain and is undergoing psychometric evaluation among a larger cohort of patients.

Insight into chronic pain in the United States: descriptive results from the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ) validation study.

OBJECTIVE: A chronic pain patient sample living in the United States who participated in a cross-sectional study to evaluate the validity and reproducibility of the Prescription Opioid Misuse and Abuse Questionnaire is characterized. METHODS: Patients with chronic pain identified through electronic medical records as refilling at least one opioid prescription within the prior 3 months were recruited from five United States Department of Defense Military Health System clinics. Patients completed the Prescription Opioid Misuse and Abuse Questionnaire, Brief Pain Inventory-Short Form, Medical Outcomes Study: 36-item Short Form, and sociodemographic questions online. Clinical characteristics and electronic medical records for 1 year prior to consent were collected. RESULTS: 809 (86.2%) participants completed the Prescription Opioid Misuse and Abuse Questionnaire. Mean (± standard deviation) age was 55.4 ± 12.7 years; the majority female (55.5%) and white (74.8%). Mean duration of chronic pain was 14.7 ± 10.5 years; the most common pain conditions were lower back pain (76.6%), neck or shoulder pain (60.3%), and osteoarthritis (38.7%). The most commonly prescribed opioids were oxycodone (35.7%), tramadol (34.5%), and hydrocodone (26.9%); 54.8% took one opioid, 44.9% took 2 or more opioids. DISCUSSION: Participants' health status was poor; pain severity and interference were moderate. Electronic medical record data revealed high healthcare resource utilization. This chronic pain population was severely impacted by their pain condition(s).

Validation of the Functional Assessment of Cancer Therapy-Leukemia instrument in patients with acute myeloid leukemia who are not candidates for intensive therapy.

BACKGROUND: The objective of this study was to validate the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) in patients with acute myeloid leukemia (AML) who are not candidates for intensive therapy. METHODS: A sample of 317 patients with AML who were not eligible for intensive chemotherapy completed the FACT-Leu and EuroQol 5-Dimension (EQ-5D) measures (Utility Index and Visual Analogue Scale) every 28 days until the end of treatment. Internal consistency reliability was estimated with Cronbach's α. Concurrent validity was examined with correlations between FACT-Leu and EQ-5D scales, and known-groups validity was examined by determining whether FACT-Leu scales distinguished between Eastern Cooperative Oncology Group (ECOG) performance status ratings (PSRs) and between maximum adverse event toxicities at the baseline. This study examined responsiveness to change by anchoring change in the FACT-Leu scales to a 0.10 change in the EQ-5D Health Utility Index. RESULTS: Cronbach's α usually exceeded the threshold for good (≥0.80) or excellent reliability (≥0.90). Correlations between FACT-Leu and EQ-5D scales were moderate (r > 0.50) or high (r > 0.70). FACT-Leu scales distinguished between ECOG PSR groups with large effect sizes for an ECOG PSR of 0 versus an ECOG PSR of 2 (0.50 ≤ d < 0.80). In addition, Functional Assessment of Cancer Therapy-General, Additional Concerns, FACT-Leu Total, and Trial Outcomes Index scales distinguished between patients with grade 3 or lower maximum adverse event toxicities and those with maximum adverse event toxicities higher than grade 3, but effect sizes were small (d < 0.50). Finally, FACT-Leu scale coefficients for a 0.10 change in the 5-level version of the EQ-5D HUI ranged between -0.01 and 4.30. CONCLUSIONS: The FACT-Leu is a suitable outcome measure for AML clinical trials among patients not eligible for intensive therapy, and it may have value for clinical monitoring.

Psychometric Validation of the Hepatitis C Symptom and Impact Questionnaire (HCV-SIQv4) in a Diverse Sample of Adults with Chronic Hepatitis C Virus Infection Treated with an Interferon-free Simeprevir-containing Regimen.

BACKGROUND: Hepatitis C virus (HCV) infection and its treatments are associated with significant symptoms, side effects and impact on patients functioning. The Hepatitis C Symptom and Impact Questionnaire version 4 (HCV-SIQv4) was developed according to FDA Patient Reported Outcomes (PRO) Guidance, for evaluating chronic HCV infection and its treatment. OBJECTIVES: This study evaluated the psychometric properties and clinically important change (CIC) thresholds of the measure. METHODS: PRO data were pooled from three Phase IIb and III trials evaluating interferon-free simeprevir-containing regimens for treatment of chronic HCV infection. Scale range adequacy, reliability, validity, responsiveness and CIC thresholds were assessed incorporating knowledge of the appropriate measurement model. RESULTS: Data from 437 patients were analyzed. Stage of liver disease was associated with symptom severity and functioning at baseline. Reliability was acceptable (test-retest ICC ≥0.7) for most scores except the Gastrointestinal and Integumentary domains. Convergent validity was observed between HCV-SIQv4 scores and concurrent measures of conceptual similarity. Greater symptom severity and worse impact scores were associated with liver cirrhosis, depression, severe fatigue and health limitations. Patients who achieved SVR12 had better outcomes than those failing to. HCV-SIQv4 symptom and domain scores were responsive to changes in health state (effect sizes ≥0.5). Exploratory thresholds for change in scores indicating a clinically important improvement and worsening were HCV-SIQv4 Overall Body System Score (BSS), 8 and 8; Constitutional BSS, 10 and 10; Gastrointestinal BSS, 5 and 5; Psychiatric BSS, 8 and 8; Neurocognitive BSS, 8 and 8; and Integumentary BSS, 5 and 5. CONCLUSIONS: The HCV-SIQv4 offers reliable, responsive assessments within HCV clinical development. CIC thresholds are now available to aid score interpretation.

Utility of Patient-Reported Outcome Instruments in Heart Failure.

Patient-reported outcomes (PRO) are defined as reports coming directly from patients about how they feel or function in relation to a health condition and its therapy. Although there are numerous compelling reasons why PRO could be an important help in clinical care, they have not evolved into clinical tools integrated into care. The purpose of this review is to assess existing PRO instruments for heart failure with respect to their psychometric properties and potential for use in clinical care. We performed a systematic search of articles published between July 2008 and January 2015 within the MEDLINE, PROMIS, PROQOLID, and Cochrane Library databases. Included instruments had to be developed and tested for heart failure and have had their development processes and psychometric properties described. A total of 31 instruments were identified, 9 of which met all inclusion criteria. After evaluating each remaining instrument in terms of psychometric and clinical criteria and symptom coverage, only 2 instruments-Minnesota Living with Heart Failure and Kansas City Cardiomyopathy questionnaire-met all evaluation criteria. Although clinically useful PRO instruments exist, increasing education to providers on the value and interpretability of PRO instruments, as well as a more streamlined approach to their implementation in the clinical setting is necessary. A clinical trial comparing the routine use of disease-specific PRO with clinical care could further support their incorporation into practice.

Concept Elicitation Within Patient-Powered Research Networks: A Feasibility Study in Chronic Lymphocytic Leukemia.

OBJECTIVES: To explore the feasibility of using social media-based patient networks to gather qualitative data on patient-reported outcome (PRO) concepts relevant to chronic lymphocytic leukemia (CLL). METHODS: Between August and November 2013, US-residing members of the PatientsLikeMe online CLL patient community completed open-ended web-based surveys designed to elicit descriptions of CLL symptoms, impacts, and treatment-related perceptions. Qualitative telephone follow-up interviews were conducted with a subsample of respondents. Survey responses and interview transcripts were coded for qualitative analysis using Atlas.ti. RESULTS: Fifty survey responses were included in the analyses. Participants were age 60.5 ± 6.9 years, 54% female, and 96% white. When surveyed, 20% were receiving current treatment, 16% were in remission, and 64% were treatment-naïve. Among respondents, 369 descriptions of CLL symptoms were coded. Fatigue-related symptoms were expressed most frequently, with 54% reporting "fatigue," "tiredness," or both in their responses. These concepts were followed by night sweats (38%), swollen lymph nodes (32%), and frequent infections (28%). Among impacts of CLL, worry and fear (66% of respondents), depressed feelings (52%), and work limitations (50%) were noted most frequently. CONCLUSIONS: Survey results identified constitutional symptoms of CLL included in existing PRO instruments and the literature. Although the findings suggest that qualitative data obtained through social media applications can be potentially useful in supporting concept identification for newly developed PRO instruments, they also indicate that online approaches alone may not be sufficient to achieve efficient and exhaustive concept elicitation. Further research is needed to identify whether the results can support content validity in the same way as established qualitative research methods.