Design Overview

We retrospectively examined the characteristics and clinical outcomes of a cohort of patients with chronic pain who received chronic opioids managed through a primary care clinic based opioid registry from 2010 to 2015, a period of substantial change in prescribing practices at the clinic. We examined reasons for discontinuation from COT, and we evaluated use of prescription opioids and continuity of primary care after discontinuation. We also compared mortality and overdose mortality of patients whose COT was discontinued with those of patients who were maintained on COT.

Study Setting

The study was performed within a large academic primary care clinic based at Harborview Medical Center in Seattle, WA, a safety-net hospital. The clinic serves approximately 4500 patients from diverse backgrounds in 20,000 visits annually. In early 2010, the clinic implemented a comprehensive effort to improve the safety of opioid prescribing for chronic pain; this included guidelines on risk assessment and monitoring (including urine screens), dosing recommendations, and the creation of an interdisciplinary panel to set clinic policies and provide management recommendations. A ceiling dose of 120 mg morphine equivalents per day (MED) was recommended and providers were encouraged to taper patients on higher doses. Once Washington State’s PDMP became fully available in January 2012, PDMP checks became routine and were entered into the electronic health record (EHR).

The clinic maintains a pharmacist-managed “opioid registry,” which serves as the organizational tool for opioid prescribing policies and procedures. Use of the registry for patients on COT is an explicit expectation of providers and is incentivized by pharmacist assistance managing refills. Discontinuing a patient from the registry involves communication between pharmacists and providers. It would be unusual and impractical for a provider to discontinue the patient from the registry while intending to continue regular opioid prescribing, making registry discharge an excellent proxy for a provider’s attempt to discontinue COT.

Study Participants

The study cohort consisted of clinic patients 18 years and older who were prescribed COT for chronic pain and enrolled in the opioid registry as of May 2010. Patients were excluded if they were prescribed opioids but not enrolled in the registry or if they joined the registry after May 2010. Patient data was collected from May 1, 2010, through March 31, 2015. Clinic policies did not specifically address opioid prescribing for patients with active malignancies; thus, these patients could be included on the registry.

Data Sources

Study data sources included the EHR, death records from the Washington State Department of Health, and clinic-based opioid registry files. Washington State death files were obtained through March 2015. Demographics, clinical data, and utilization data were electronically abstracted from the EHR and merged with death records using unique identifiers. Opioid registry files included Microsoft Excel spreadsheets managed by clinic pharmacists and Washington State PDMP data; the PDMP was queried for all registry patients as part of a quality improvement effort in 2015 and the results were added to the patient’s clinic opioid registry records. The Washington State PDMP documents all scheduled medication prescriptions filled throughout the state; its use was mandatory for non-Veterans Affairs pharmacies by January 2012.

Dates and reasons for discontinuation of COT and prescription data were abstracted through chart review of the EHR and clinic opioid registry files and imported into a study database in REDCap.

Definition of COT

Our primary exposure of interest was discontinuation of COT, represented by discontinuation from the opioid registry. Patients who were on the clinic opioid registry as of May 1, 2010, and remained on the registry through March 2015, or who died while on the registry, were considered to have continued COT. Those who were removed from the registry at any point during the study period for any reason other than death were considered to have had COT discontinued. We did not determine COT duration for each patient, as registry data did not include COT initiation dates. The date of discontinuation was often directly recorded in opioid registry files or in telephone or visit notes in the EHR; if not, it was calculated by adding days’ supply to the date of the last continuous monthly prescription by the prescribing provider, using PDMP data. If the date was unavailable based on these methods (PDMP data was not available prior to 2012), it was approximated as the midway point between the dates at which the patient was present and absent from the opioid registry files. Because versions of these files were saved on a roughly monthly basis, these estimated dates would differ minimally from the actual dates. For patients who died within 30 days of the date of discontinuation, additional chart review was performed to determine whether death occurred prior to or following discontinuation.

The small number of patients who had COT discontinued but later returned to the registry were still categorized as having had COT discontinued, as their primary care provider had made a decision to discontinue opioids at least once.

Measures

To assess characteristics of our study cohort, we abstracted demographic information (age at baseline, sex, race/ethnicity, language, marital status, and insurance status); substance use, mental health, and other medical diagnoses; and prescription of controlled medications. Diagnoses were abstracted from all available EHR data. Baseline opioid dose was determined by examining opioid registry Excel files for the period prior to discontinuation and identifying the first of three consecutive opioid prescriptions written by the same prescriber for the same opioid medication, dose, and number of tablets. It was converted to morphine equivalent dose (MED)10 and summed, in the case of multiple prescribed opioids.

For the discontinued group, we characterized subsequent opioid prescriptions according to PDMP records. Patients were not reclassified with regard to opioid registry status based on retrospective review of PDMP records. To assess continuity of primary care, clinic and hospital visit data were electronically abstracted from the EHR. All patients continued in the registry were assumed to have completed regular primary care visits, as this was required for ongoing receipt of COT.

All-cause mortality and death due to overdose were assessed for all patients. Death by overdose was characterized as definite or possible based on a priori classification of information provided to the Washington State Department of Health by the medical examiner or other certifying physician. Death due to definite overdose was assigned when death records specified drug overdose or intoxication; death due to possible overdose was assigned to deaths due to respiratory failure (Supplement). A composite of definite and possible overdose was used in the analysis of overdose-related death.

Characterization of Reasons for Discontinuation

In many cases, a reason for discontinuation was noted explicitly in opioid registry files; in other cases, contributing reasons appeared in provider and pharmacist notes. Multiple reasons for COT discontinuation could be recorded. Abstraction of reasons for COT discontinuation was performed by one co-author (MN); several co-authors (SJ, JJ, JK, JM) independently reviewed 10% of patients’ records and found > 95% concordance. Specific reasons for COT discontinuation were listed, grouped (MN, JK), and analyzed through an iterative process to identify key patterns. Reasons deemed similar from a clinical perspective were combined. Because each participant could have multiple reasons for discontinuation listed, the total number of unique individuals in each category was determined. Reasons that were most common and/or most clinically significant were selected for inclusion in the results.

Statistical Analyses

Descriptive statistics were calculated for variables of interest. Frequencies were calculated for each category of reasons for COT discontinuation. Cox proportional hazard models adjusting for age and race were used to determine associations between discontinuation of COT and all-cause mortality and between discontinuation of COT and death due to overdose. Fisher’s exact test was used to determine associations between reasons for discontinuation of COT and overdose death. The significance level was set to 0.05. All analysis was performed in Stata 14.2 (StataCorp LP, College Station, TX).

Institutional Review

The study was approved by the Institutional Review Board at the University of Washington.