Health-care resource use among patients who use illicit opioids in England, 2010-20: A descriptive matched cohort study.

BACKGROUND AND AIMS: People who use illicit opioids have higher mortality and morbidity than the general population. Limited quantitative research has investigated how this population engages with health-care, particularly regarding planned and primary care. We aimed to measure health-care use among patients with a history of illicit opioid use in England across five settings: general practice (GP), hospital outpatient care, emergency departments, emergency hospital admissions and elective hospital admissions. DESIGN: This was a matched cohort study using Clinical Practice Research Datalink and Hospital Episode Statistics. SETTING: Primary and secondary care practices in England took part in the study. PARTICIPANTS: A total of 57 421 patients with a history of illicit opioid use were identified by GPs between 2010 and 2020, and 172 263 patients with no recorded history of illicit opioid use matched by age, sex and practice. MEASUREMENTS: We estimated the rate (events per unit of time) of attendance and used quasi-Poisson regression (unadjusted and adjusted) to estimate rate ratios between groups. We also compared rates of planned and unplanned hospital admissions for diagnoses and calculated excess admissions and rate ratios between groups. FINDINGS: A history of using illicit opioids was associated with higher rates of health-care use in all settings. Rate ratios for those with a history of using illicit opioids relative to those without were 2.38 [95% confidence interval (CI) = 2.36-2.41] for GP; 1.99 (95% CI = 1.94-2.03) for hospital outpatient visits; 2.80 (95% CI = 2.73-2.87) for emergency department visits; 4.98 (95% CI = 4.82-5.14) for emergency hospital admissions; and 1.76 (95% CI = 1.60-1.94) for elective hospital admissions. For emergency hospital admissions, diagnoses with the most excess admissions were drug-related and respiratory conditions, and those with the highest rate ratios were personality and behaviour (25.5, 95% CI = 23.5-27.6), drug-related (21.2, 95% CI = 20.1-21.6) and chronic obstructive pulmonary disease (19.4, 95% CI = 18.7-20.2). CONCLUSIONS: Patients who use illicit opioids in England appear to access health services more often than people of the same age and sex who do not use illicit opioids among a wide range of health-care settings. The difference is especially large for emergency care, which probably reflects both episodic illness and decompensation of long-term conditions.

Use of Minimal Residual Disease Status to Reduce Uncertainty in Estimating Long-term Survival Outcomes for Newly Diagnosed Multiple Myeloma Patients.

Background: Demonstrating the cost-effectiveness of new treatments for multiple myeloma (MM) often relies on the extrapolation of overall survival (OS) trial data. This method can introduce uncertainty in long-term survival estimates if OS data are immature, as is often the case in newly diagnosed MM (NDMM). We explore the use of the relationship between minimal residual disease (MRD) status and OS to reduce uncertainty of long-term survival outcomes. Objectives: To evaluate if uncertainty in long-term modeled outcomes in NDMM is reduced using a response-based partitioned survival model (PSM), whereby patients were categorized as MRD-positive or -negative, relative to a standard PSM, when OS data are immature. Methods: Standard and response-based PSMs, estimating patient life-years (LYs) over a lifetime horizon, were developed for NDMM patients treated with bortezomib, thalidomide, and dexamethasone (BTd) with or without daratumumab as induction and consolidation therapy. In the standard PSM, LYs were determined by extrapolations from individual patient data from CASSIOPEIA. In the response-based PSM, survival was dependent on MRD status at the time of the response assessment via a landmark analysis. Cox-proportional hazard ratios from external sources and CASSIOPEIA informed the relationship for OS between MRD-positive and MRD-negative, and between patients receiving BTd and daratumumab plus BTd, respectively. Uncertainty was assessed by comparing LYs and OS extrapolations from deterministic and probabilistic analyses. Results: This response-based PSM demonstrated reduced uncertainty in long-term survival outcomes compared with the standard PSM (range across extrapolations of 3.4 and 7.7 LYs for daratumumab plus BTd and BTd, respectively, vs 14.8 and 11.8 LYs for the standard PSM). It also estimated a narrower interquartile range of LYs in the probabilistic analyses for the majority of parametric extrapolations. Discussion: Alternative methods to estimate long-term survival outcomes, such as a response-based PSM, can reduce uncertainty in modeling predictions around cost-effectiveness estimates for health technology assessment bodies and payers, thereby supporting faster market access for novel therapies with immature survival data. Conclusions: Use of MRD status in a response-based PSM reduces uncertainty in modeling long-term survival in patients with NDMM and provides a greater number of clinically plausible extrapolations compared with a standard PSM.

Causes of death among people who used illicit opioids in England, 2001-18: a matched cohort study.

BACKGROUND: In many countries, the average age of people who use illicit opioids, such as heroin, is increasing. This has been suggested to be a reason for increasing numbers of opioid-related deaths seen in surveillance data. We aimed to describe causes of death among people who use illicit opioids in England, how causes of death have changed over time, and how they change with age. METHODS: In this matched cohort study, we studied patients in the Clinical Practice Research Datalink with recorded illicit opioid use (defined as aged 18-64 years, with prescriptions or clinical observations that indicate use of illicit opioids) in England between Jan 1, 2001, and Oct 30, 2018. We also included a comparison group, matched (1:3) for age, sex, and general practice with no records of illicit opioid use before cohort entry. Dates and causes of death were obtained from the UK Office for National Statistics. The cohort exit date was the earliest of date of death or Oct 30, 2018. We described rates of death and calculated cause-specific standardised mortality ratios. We used Poisson regression to estimate associations between age, calendar year, and cause-specific death. FINDINGS: We collected data for 106 789 participants with a history of illicit opioid use, with a median follow-up of 8·7 years (IQR 4·3-13·5), and 320 367 matched controls with a median follow-up of 9·5 years (5·0-14·4). 13 209 (12·4%) of 106 789 participants in the exposed cohort had died, with a standardised mortality ratio of 7·72 (95% CI 7·47-7·97). The most common causes of death were drug poisoning (4375 [33·1%] of 13 209), liver disease (1272 [9·6%]), chronic obstructive pulmonary disease (COPD; 681 [5·2%]), and suicide (645 [4·9%]). Participants with a history of illicit opioid use had higher mortality rates than the comparison group for all causes of death analysed, with highest standardised mortality ratios being seen for viral hepatitis (103·5 [95% CI 61·7-242·6]), HIV (16·7 [9·5-34·9]), and COPD (14·8 [12·6-17·6]). In the exposed cohort, at age 20 years, the rate of fatal drug poisonings was 271 (95% CI 230-313) per 100 000 person-years, accounting for 59·9% of deaths at this age, whereas the mortality rate due to non-communicable diseases was 31 (16-45) per 100 000 person-years, accounting for 6·8% of deaths at this age. Deaths due to non-communicable diseases increased more rapidly with age (1155 [95% CI 880-1431] deaths per 100 000 person-years at age 50 years; accounting for 52·0% of deaths at this age) than did deaths due to drug poisoning (507 (95% CI 452-562) per 100 000 person-years at age 50 years; accounting for 22·8% of deaths at this age). Mirroring national surveillance data, the rate of fatal drug poisonings in the exposed cohort increased from 345 (95% CI 299-391) deaths per 100 000 person-years in 2010-12 to 534 (468-600) per 100 000 person-years in 2016-18; an increase of 55%, a trend that was not explained by ageing of participants. INTERPRETATION: People who use illicit opioids have excess risk of death across all major causes of death we analysed. Our findings suggest that population ageing is unlikely to explain the increasing number of fatal drug poisonings seen in surveillance data, but is associated with many more deaths due to non-communicable diseases. FUNDING: National Institute for Health Research.