Postmarketing studies program to assess the risks and benefits of long-term use of extended-release/long-acting opioids among chronic pain patients

Figures & data

Figure 1. Conceptual Framework of the Observational Studies and Randomized Clinical Trial in the ER/LA Opioid Postmarketing Study Program.

DPS, doctor/pharmacy shopping; ER/LA, extended-release/long-acting; OUD, opioid-use disorder; PRISM, Psychiatric Research Interview for Substance and Mental Disorders, Fifth Edition, Opioid Study Version.

Table 1. List of Studies in the ER/LA Opioid Postmarketing Study Program, their Goals and ClinicalTrials.gov Number.

PMR Study Number (NCT Number)	Goal of Individual Studies
3033-1 (NCT02751762)	Prospective cohort study enrolling 2,400 pain patients prescribed opioid analgesics to assess incidence and predictors of misuse, abuse, and addiction
3033-2 (NCT02662153)	Retrospective database cohort study of patients prescribed ER/LA or IR opioid analgesics to assess incidence and predictors of overdose and death among long-term users in 4 (2 electronic health record, 1 large claims and 1 state Medicaid) databases
3033-3 (NCT02678507)	Validate measure of patient-reported misuse and abuse (POMAQ) for content validity and patient interpretation
3033-4 (NCT02660606)	Validate measure of patient-reported misuse and abuse (POMAQ) for validity and reproducibility
3033-5 (NCT02660619)	Validate PRISM-5-OP measure of patient-reported prescription opioid use disorder (addiction)
3033-6 (NCT02667197)	Validate algorithms using coded terms in databases to identify overdose and death in Study 2 databases
3033-7 (NCT02667262)	Validate algorithms using coded terms in databases to identify abuse or addiction in Study 2 databases
3033-8 (NCT02668549)	Define and validate ‘doctor/pharmacy shopping’ as an outcome suggestive of abuse/addiction using the algorithms produced by Study 7
3033-9 (NCT02667158)	Validate ‘doctor/pharmacy shopping’ as an outcome suggestive of misuse and or abuse based on patient responses to the POMAQ survey
3033-10 (NCT02667210)	Evaluate the association between ‘doctor/pharmacy shopping’ and patient behaviors suggestive of misuse, abuse, and addiction described in medical charts
3033-11 (NCT02741076)	Clinical trial of structured ER/LA opioid withdrawal to measure efficacy of long-term opioid treatment for chronic pain and the occurrence of opioid-induced hyperalgesia. (This study has been discontinued and a new study design is under discussion with FDA)

ER/LA = extended-release/long-acting; IR = immediate-release; PMR = postmarketing requirement; POMAQ = Prescription Opioid Misuse and Abuse Questionnaire; PRISM = Psychiatric Research Interview for Substance & Mental Disorders.

Figure 2. Conceptual Framework for ER/LA Opioid Observational Studies Linking Goals to Measurement Tools, Design, Study Sites/Databases and Validation of Measurement Tools.

Table 2. Summary of Study Design, Data Sources, Population and Outcome Measures for 10 Postmarketing Safety Requirement Studies.

PMR Study Number (NCT Number)	Design	Data Sources	Study Population	Study Outcome Measure
Study 1: 3033–1 (NCT02751762) [17]	Prospective, longitudinal cohort study of patients initiating opioids; cross-sectional study of opioid patients	patient-reported outcomes (PROs), in-person interviews, web-based assessments, electronic medical record (EMR) and claims data	2,300 patients	Incidence and risk factors for misuse, abuse and addiction 1 year after starting opioids
Study 2: 3033–2 (NCT02662153) [18]	Retrospective inception cohort	Claims data from 4 healthcare systems	All patients 18 to 79 years dispensed Schedule II opioids (sample size depends on database)	Cumulative incidence of opioid overdose or death, and risk factors
Study 3: 3033–3 (NCT02678507) [19]	Qualitative cross-sectional study	qualitative data from cognitive interviews; POMAQ, Brief Pain Inventory-Short Form (BPI-SF), and a sociodemographic questionnaire online	56 adults	Content analysis of qualitative data from cognitive interviews
Study 4: 3033–4 (NCT02660606) [20]	Quantitative cross-sectional validation study	PROs completed via a web-based survey including the POMAQ, BPI-SF, Prescription Drug Use Questionnaire-Patient version (PDUQp), Socially Desirable Response Set Five-item Survey (SRDS-5), Medical Outcomes Study	809 pain patients with opioid prescriptions	Construct validation comparing POMAQ outcomes to other measures
Study 5: 3033–5 (NCT02660619) [21]	Cross-sectional evaluation to assess construct validity	PRISM-5-Op interviews, self-administered questionnaires, medical records, expert clinician review	Patients with opioid prescriptions for ≥30 days: 300 low-risk and 300 high-risk patients	Opioid use disorder using DSM-5 criteria compared to other measures
Study 6: 3033–6 (NCT02667197) [22]	Retrospective validation study comparing people with ICD overdose codes with medical chart review	Model developed in Kaiser Permanente Northwest EMR and validated in claims, Medicaid and EMR databases	Subjects with overdose were 1,006 in Development sample and 1,695 in Validation Sample	Algorithm-identified overdose compared to chart abstraction gold standard
Study 7: 3033–7 (NCT02667262) [23]	Retrospective validation study comparing problematic opioid use with medical chart review	Model developed in Kaiser Permanente Washington EMR and validated in claims, Medicaid and EMR data	All patients aged 18 to 79 years dispensed Schedule II opioids in database (sample size depends on database)	Algorithm-identified abuse/addiction compared to chart abstraction gold standard
Study8: 3033–8 (NCT02668549) [24]	Retrospective cohort	longitudinal pharmacy database (IQVIA LRx) linked to claims database (IQVIA PharMetrics Plus)	over 8 million subjects with ≥2 opioid dispensings in 18-months	Shopping behavior categories compared with abuse/addiction algorithm
Study 9: 3033–9 (NCT02667158) [25]	Retrospective cohort and survey	Claims database (HealthCore) to assess opioid shopping and POMAQ survey to measure abuse/addiction	1084 patients recruited and asked to complete POMAQ survey	Shopping behavior classification categories compared with POMAQ questionnaire scores
Study 10: 3033–10 (NCT02667210) [26]	Retrospective cohort	Claims database (HealthCore) to measure opioid shopping and medical chart review to measure abuse and addiction	590 patients in the different shopping categories	Shopping behavior categories compared with misuse, diversion, abuse, or addiction behaviors in medical charts

ER/LA = extended-release/long-acting; IR = immediate-release; PMR = postmarketing requirement; POMAQ = Prescription Opioid Misuse and Abuse Questionnaire; PRISM = Psychiatric Research Interview for Substance & Mental Disorders.

Opioid PMR Consortium. A prospective investigation of the risks of opioid misuse, abuse, and addiction among patients treated with extended-release/Long Acting (ER/LA) Opioids for the treatment of chronic pain www.clinicaltrials.gov. Identifier: NCT02751762. [cited 2018 Jul 13]. Available from: https://clinicaltrials.gov/ct2/show/NCT02751762?term=opioid+PMR&rank=5

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Opioid PMR Consortium. Incidence and predictors of opioid overdose and death in ER/LA opioid users as measured by diagnoses and death records. www.clinicaltrials.gov. Identifier: NCT02662153. [cited 2018 Jan 29]. Available from: https://clinicaltrials.gov/show/NCT02662153

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Opioid PMR Consortium. A quantitative study to assess the construct validity of the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ). www.clinicaltrials.gov. Identifier: NCT02678507. [cited 2018 Jan 29]. Available from: https://clinicaltrials.gov/show/NCT02678507

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Opioid PMR Consortium. A qualitative study to assess the content validity of the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ). www.clinicaltrials.gov. Identifier: NCT02660606. [cited 2018 Jan 29]. Available from: https://clinicaltrials.gov/show/NCT02660606

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Opioid PMR Consortium. Validation of PRISM-5-Op, measure of addiction to prescription opioid medication. www.clinicaltrials.gov. Identifier: NCT02660619. [cited 2018 Jan 29]. Available from: https://clinicaltrials.gov/show/NCT02660619

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Opioid PMR Consortium. Study to validate coded medical terms used to identify opioid-related overdose in databases used for PMR study 1B. www.clinicaltrials.gov. Identifier: NCT02667197. [cited 2018 Jan 29]. Available from: https://clinicaltrials.gov/show/NCT02667197

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Opioid PMR Consortium. An observational study to develop algorithms for identifying opioid abuse and addiction based on admin claims data. www.clinicaltrials.gov. Identifier: NCT02667262. [cited 2018 Jan 29]. Available from: https://clinicaltrials.gov/show/NCT02667262

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Opioid PMR Consortium. Cross-Sectional Study to Define and Validate “Doctor/Pharmacy Shopping” as Outcomes Suggestive of Abuse and/or Addiction. www.clinicaltrials.gov. Identifier: NCT02668549. [cited 2018 Jan 29]. Available from: https://clinicaltrials.gov/show/NCT02668549

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Opioid PMR Consortium. A survey to evaluate the relationship between Doctor/Pharmacy Shopping and outcomes suggestive of misuse, abuse and/or Diversion. www.clinicaltrials.gov. Identifier: NCT02667158. cited 2018 Jan 29. Available from: https://clinicaltrials.gov/show/NCT02667158

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Opioid PMR Consortium. Study to Evaluate the Relationship Between Doctor/Pharmacy Shopping & Outcomes of Misuse, Diversion, Abuse, Addiction by Medical Record Review. www.clinicaltrials.gov. Identifier: NCT02667210. cited 2019 Nov 2. Available from: https://clinicaltrials.gov/ct2/show/NCT02667210

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