Karen P Hayhurst

A Randomized Controlled Trial of the Cost‐Utility of Second‐Generation Antipsychotics in People with Psychosis and Eligible for Clozapine

OBJECTIVE To assess whether clozapine is likely to be more cost-effective than other second-generation antipsychotics (SGAs) in people with schizophrenia. METHODS An integrated clinical and economic multicenter, rater-blind, randomized controlled trial (RCT) compared clozapine to the class of other SGAs, using the perspectives of the National Health Service, social support services, and patients. The practice setting was secondary and primary care in the United Kingdom; patients were followed for 1 year. Incremental cost-effectiveness ratios (ICERs), net benefit statistics, and cost acceptability curves were estimated. RESULTS The ICER for clozapine was 33,240 pound per quality-adjusted life-year (QALY) (range 23,000-70,000 pound for the sensitivity analyses). The proportion of simulations when clozapine was more cost-effective than other SGAs reached 50% if decision-makers are prepared to pay 30,000 pound to 35,000 pound per QALY. This is at the top of the range of acceptable willingness-to-pay values per QALY implied by decisions taken by the National Institute for Health and Clinical Excellence (NICE). CONCLUSIONS This study adds to a limited body of evidence comparing clozapine to other SGAs and is the first economic and clinical RCT to compare clozapine to the class of other SGAs using the lower cost of generic clozapine and a pragmatic trial design. Policy decisions by the NICE suggest that additional reasons would be needed to accept clozapine as effective and efficient if it had a high probability of having ICERs more than 35,000 pound per QALY. The results and limitations of the analysis suggest that there is still a need for further economic evaluation of clozapine.

The cost-effectiveness of clozapine: A controlled, population-based, mirror-image study

A retrospective cohort study, with a mirror-image design, was used to measure inpatient service utilization in 63 consecutive patients started on clozapine from a geographical catchment area compared to a control group matched for previous inpatient service use. An intent-to-treat analysis, including those patients (n = 28) who discontinued clozapine during the study period, showed a significant reduction in number of admissions and total time spent in hospital in the 2 years following clozapine initiation compared to the previous 2 years and to the follow-up period in the control group. This translated into a reduction of £7300 in hospitalization costs per patient started on clozapine, over the 2-year period. In those patients who continued clozapine treatment for the whole of the 2-year period, there was a two-thirds reduction in number of admissions and total time spent in hospital compared to no change in the clozapine discontinuers. These findings suggest that clozapine is a clinically and cost-effective intervention for severe schizophrenia in routine clinical settings.

Validity of subjective versus objective quality of life assessment in people with schizophrenia

BackgroundQuality of life (QoL) is considered an important outcome in health research. It can be rated by the patient, or by an external assessor. We wished to identify the predictors of any discrepancies between these two approaches in people with schizophrenia.MethodsPatients with DSM schizophrenia and related disorders (N = 80) completed both patient-rated (Lancashire Quality of Life Profile; LQOLP) and assessor-rated (Heinrich’s Quality of Life Scale; QLS) measures of QoL.ResultsPatient-rated (LQOLP) and assessor-rated (QLS) measures showed a modest correlation (r = 0.38). In a regression analysis, independent predictors of subjectively-rated QoL being higher than objectively-assessed QoL in the same patient, were low insight score (BIS), negative symptoms (PANSS), absence of depression (CDSS), and less positive attitude toward prescribed treatment (DAI).ConclusionsIn people with schizophrenia, scores on objectively- and subjectively-rated measures of quality of life can differ markedly. When comparing subjective to objective assessments, patients with depressive symptoms will value their QoL lower, and those with low insight will value their QoL higher. This has important implications for the utility and interpretation of QoL measures in schizophrenia.

Improved quality of life over one year is associated with improved adherence in patients with schizophrenia

AIM Quality of life (QoL) is increasingly considered an important outcome in health research. We wished to explore the determinants of change in QoL in patients with schizophrenia over the course of a one-year RCT. METHODS Predictors of change in observer-rated QoL (Quality of Life Scale: QLS) were assessed in 363 patients with schizophrenia during the CUtLASS clinical trial. RESULTS Change in QLS score over the course of a year correlated with change in psychotic and depressive symptoms and treatment adherence. Linear regression showed that improvement in QoL was predicted by reduction in negative and depressive symptoms and improvement in adherence rating. These three change scores together explained 38% of the variance in QLS change. Exploration of the direction of any possible causal effect, using TETRAD, indicated that improved adherence leads to improved QoL, and that change in depression also leads to QoL change. The relationship between QoL and negative symptoms suggests that greater social activity (reflected as better QoL scores) improves negative symptoms. Such a direct relationship between treatment adherence and QoL has not been reported before. CONCLUSION Improving adherence to medication would appear to be a key approach to improving measured quality of life in people with schizophrenia.

The effectiveness and cost-effectiveness of diversion and aftercare programmes for offenders using class A drugs: a systematic review and economic evaluation

BACKGROUND The societal costs of problematic class A drug use in England and Wales exceed £15B; drug-related crime accounts for almost 90% of costs. Diversion plus treatment and/or aftercare programmes may reduce drug-related crime and costs. OBJECTIVES To assess the effectiveness and cost-effectiveness of diversion and aftercare for class A drug-using offenders, compared with no diversion. POPULATION Adult class A drug-using offenders diverted to treatment or an aftercare programme for their drug use. INTERVENTIONS Programmes to identify and divert problematic drug users to treatment (voluntary, court mandated or monitored services) at any point within the criminal justice system (CJS). Aftercare follows diversion and treatment, excluding care following prison or non-diversionary drug treatment. DATA SOURCES Thirty-three electronic databases and government online resources were searched for studies published between January 1985 and January 2012, including MEDLINE, PsycINFO and ISI Web of Science. Bibliographies of identified studies were screened. The UK Drug Data Warehouse, the UK Drug Treatment Outcomes Research Study and published statistics and reports provided data for the economic evaluation. METHODS Included studies evaluated diversion in adult class A drug-using offenders, in contact with the CJS. The main outcomes were drug use and offending behaviour, and these were pooled using meta-analysis. The economic review included full economic evaluations for adult opiate and/or crack, or powder, cocaine users. An economic decision analytic model, estimated incremental costs per unit of outcome gained by diversion and aftercare, over a 12-month time horizon. The perspectives included the CJS, NHS, social care providers and offenders. Probabilistic sensitivity analysis and one-way sensitivity analysis explored variance in parameter estimates, longer time horizons and structural uncertainty. RESULTS Sixteen studies met the effectiveness review inclusion criteria, characterised by poor methodological quality, with modest sample sizes, high attrition rates, retrospective data collection, limited follow-up, no random allocation and publication bias. Most study samples comprised US methamphetamine users. Limited meta-analysis was possible, indicating a potential small impact of diversion interventions on reducing drug use [odds ratio (OR) 1.68, 95% confidence interval (CI) 1.12 to 2.53 for reduced primary drug use, and OR 2.60, 95% CI 1.70 to 3.98 for reduced use of other drugs]. The cost-effectiveness review did not identify any relevant studies. The economic evaluation indicated high uncertainty because of variance in data estimates and limitations in the model design. The primary analysis was unclear whether or not diversion was cost-effective. The sensitivity analyses indicated some scenarios where diversion may be cost-effective. LIMITATIONS Nearly all participants (99.6%) in the effectiveness review were American (Californian) methamphetamine users, limiting transfer of conclusions to the UK. Data and methodological limitations mean it is unclear whether or not diversion is effective or cost-effective. CONCLUSIONS High-quality evidence for the effectiveness and cost-effectiveness of diversion schemes is sparse and does not relate to the UK. Importantly this research identified a range of methodological limitations in existing evidence. These highlight the need for research to conceptualise, define and develop models of diversion programmes and identify a core outcome set. A programme of feasibility, pilot and definitive trials, combined with process evaluation and qualitative research is recommended to assess the effectiveness and cost-effectiveness of diversionary interventions in class A drug-using offenders. FUNDING DETAILS The National Institute for Health Research Health Technology Assessment programme.

Drug spend and acquisitive offending by substance misusers

AIM The need to generate income to fund drug misuse is assumed to be a driver of involvement in acquisitive crime. We examined the influence of drug misuse expenditure, and other factors, on acquisitive offending. METHODS Clients (N=1380) seeking drug treatment within 94 of 149 Drug Action Teams (DATs) across England completed a comprehensive survey, incorporating validated scales and self-report measures, such as levels of drug and alcohol use and offending. RESULTS Forty per cent (N=554) had committed acquisitive crime in the previous month. Regression analysis showed that acquisitive offending was associated with the presence of problematic use of crack cocaine, poly-drug use, sharing injecting equipment, unsafe sex, overdose risk, higher drug spend, unemployment, reduced mental wellbeing, and younger age. CONCLUSIONS Rates of acquisitive crime among drug users are high. Drug using offenders can be distinguished from drug using non-offenders by problematic crack cocaine use, younger age, income-related factors, and indicators of a chaotic life style and complex needs. Behavioural and demographic factors were associated more strongly with acquisitive crime than drug use expenditure, suggesting that the need to finance drug use is not necessarily the main factor driving acquisitive offending by drug users.

Effect of prior treatment with antipsychotic long-acting injection on randomised clinical trial treatment outcomes

BACKGROUND It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations. AIMS To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence. METHOD Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study). RESULTS Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA. CONCLUSIONS A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.

Quantifying crime associated with drug use among a large cohort of sanctioned offenders in England and Wales

Highlights • Opiate use is associated with elevated (acquisitive and non-acquisitive) offending.• The association between drug use and crime is stronger for women than men.• Cocaine use is associated with offending among males but not among females.• Opiate and cocaine use is associated with 25 times the rate of prostitution (females only).

The ANNSERS (Antipsychotic Non-Neurological Side Effects Rating Scale): validation of sexual side-effect measurement:

Antipsychotic nonneurological side effects, such as sexual dysfunction, can adversely affect the quality of patients’ relationships, their treatment adherence and their quality of life. In the UK CUtLASS (Cost Utility of the Latest Antipsychotics in Severe Schizophrenia) study, nonneurological side effects were assessed using the ANNSERSv1 (Antipsychotic Non-Neurological Side Effects Rating Scale version 1), a new scale to assess the side effects associated with both first- and second-generation antipsychotic drugs. A total of 26 participants also completed the Derogatis Interview for Sexual Functioning (self-report version, DISF-SR). A statistically significant, and specific, correlation was found between scores on the DISF-SR and the sexual side-effect section of the ANNSERS at baseline. The sexual side-effects subscale of the ANNSERS is a valid measure of sexual dysfunction in the treatment of schizophrenia.

The Drug Treatment Outcomes Research Study (DTORS): research design and baseline data

The Drug Treatment Outcomes Research Study (DTORS) is the more recent of two such major English studies. Over the past decade, a substantial policy shift has emphasised the role of treatment in diverting drug misusing offenders from the criminal justice system. At the same time, changes in the drug-using population, particularly increasing levels of crack cocaine use, have led to an acute need to evaluate the extent to which drug treatment works. DTORS consists of three components: the main, quantitative element tracking the treatment progress of N=1,796 drug treatment seekers; qualitative work using data from a sample of treatment seekers and treatment providers; and a cost effectiveness analysis. This paper provides an overview of the methods used for the main quantitative element; a longitudinal, nationwide, multi- site, observational, cohort study using survey interviews to assess the impact of treatment on drug use, offending, and health. An overview of the DTORS baseline sample is provided and compared with the target population of drug treatment seekers in England. Participants were drug users seeking treatment from community based or residential treatment services, assessed at baseline and followed up over a 12-month period. The baseline DTORS sample was predominantly male (73%) and aged 25 to 34 (47%). Primary problem drugs included heroin (57%) and crack (12%) with drugs used in the month prior to baseline having a mean value of £1,213. 72% committed offences in the 12 months before recruitment, most commonly shoplifting or buying and selling stolen goods.