Mobile telephone delivered contingency management for encouraging adherence to supervised methadone consumption: feasibility study for an RCT of clinical and cost-effectiveness (TIES).

BACKGROUND: Prescription methadone or buprenorphine enables people with opioid use disorder to stop heroin use safely while avoiding withdrawal. To ensure methadone is taken as prescribed and to prevent diversion onto the illicit market, people starting methadone take their daily dose under a pharmacist's supervision. Many patients miss their daily methadone dose risking withdrawal, craving for heroin and overdose due to loss of heroin tolerance. Contingency management (CM) can improve medication adherence, but remote delivery using technology may be resource-light and cost-effective. We developed an innovative way to deliver CM by mobile telephone. Software monitors patients' attendance and supervised methadone consumption through an internet self-login at the pharmacy and sends reinforcing text messages to patients' mobile telephones. A linked system sends medication adherence reports to prescribers and provides early warning alerts of missed doses. A pre-paid debit card system provides financial incentives. METHODS: A cluster randomised controlled trial design was used to test the feasibility of conducting a future trial of mobile telephone CM to encourage adherence to supervised methadone in community pharmacies. Each cluster (drug service/3 allied pharmacies) was randomly allocated to provide patient's presenting for a new episode of opiate agonist treatment (OAT) with either (a) mobile telephone text message CM, (b) mobile telephone text message reminders, or (c) no text messages. We assessed acceptability of the interventions, recruitment, and follow-up procedures. RESULTS: Four drug clinics were approached and three recruited. Thirty-three pharmacists were approached and 9 recruited. Over 3 months, 173 individuals were screened and 10 enrolled. Few patients presented for OAT and high numbers were excluded due to receiving buprenorphine or not attending participating pharmacies. There was 96% consistency in recording medication adherence by self-login vs. pharmacy records. In focus groups, CM participants were positive about using self-login, the text messages, and debit card. Prescribers found weekly reporting, time saving, and allowed closer monitoring of patients. Pharmacists reported that the tablet device was easy to host. CONCLUSION: Mobile telephone CM worked well, but a planned future trial will use modified eligibility criteria (existing OAT patients who regularly miss their methadone/buprenorphine doses) and increase the number of participating pharmacies. TRIAL REGISTRATION: The trial is retrospectively registered, ISRCTN 58958179 .

Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study).

BACKGROUND: Approximately 30-50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group. METHODS: The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open-label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical and cost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects. DISCUSSION: The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16387615 , registered 28 February 2016. ClinicalTrials.gov: NCT03004521 , registered 17 November 2016.

Clinical and cost-effectiveness analysis of an open label, single-centre, randomised trial of spinal cord stimulation (SCS) versus percutaneous myocardial laser revascularisation (PMR) in patients with refractory angina pectoris: The SPiRiT trial.

BACKGROUND: Patients with refractory angina have significant morbidity. This study aimed to compare two of the treatment options, Spinal Cord Stimulation (SCS) and Percutaneous Myocardial Laser Revascularisation (PMR) in terms of clinical outcomes and cost-effectiveness. METHODS: Eligible patients were randomised to PMR or SCS and followed up for exercise tolerance time (ETT), Canadian Cardiovascular Society (CCS) classification and the quality of life measures SF-36, Seattle Angina Questionnaire and the EuroQoL at 3, 12 and 24 months. Utilities were calculated using the EQ-5D and these and costs were compared between groups. The incremental cost-effectiveness ratio (ICER) per QALY for SCS compared to PMR was also calculated. RESULTS: At 24 months post-randomisation, patients that had SCS and PMR had similar ETT (mean difference 0.05, 95% CI -2.08, 2.18, p = 0.96) and there was no difference in CCS classification or quality of life outcomes. The difference in overall mean costs when comparing SCS to PMR was GBP5,520 (95% CI GBP1,966 to GBP8,613; p < 0.01) and the ICER of using SCS was GBP46,000 per QALY. CONCLUSION: Outcomes after SCS did not differ appreciably from those after PMR, with the former procedure being less cost-effective as currently applied. Larger studies could clarify which patients would most benefit from SCS, potentially increasing cost-effectiveness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN09648950.

Cost-effectiveness of functional cardiac testing in the diagnosis and management of coronary artery disease: a randomised controlled trial. The CECaT trial.

OBJECTIVES: To assess the acceptability and feasibility of functional tests as a gateway to angiography for management of coronary artery disease (CAD), the ability of diagnostic strategies to identify patients who should undergo revascularisation, patient outcomes in each diagnostic strategy, and the most cost-effective diagnostic strategy for patients with suspected or known CAD. DESIGN: A rapid systematic review of economic evaluations of alternative diagnostic strategies for CAD was carried out. A pragmatic and generalisable randomised controlled trial was undertaken to assess the use of the functional cardiac tests: angiography (controls); single photon emission computed tomography (SPECT); magnetic resonance imaging (MRI); stress echocardiography. SETTING: The setting was Papworth Hospital NHS Foundation Trust, a tertiary cardiothoracic referral centre. PARTICIPANTS: Patients with suspected or known CAD and an exercise test result that required non-urgent angiography. INTERVENTIONS: Patients were randomised to one of the four initial diagnostic tests. MAIN OUTCOME MEASURES: Eighteen months post-randomisation: exercise time (modified Bruce protocol); cost-effectiveness compared with angiography (diagnosis, treatment and follow-up costs). The aim was to demonstrate equivalence in exercise time between those randomised to functional tests and those randomised to angiography [defined as the confidence interval (CI) for mean difference from angiography within 1 minute]. RESULTS: The 898 patients were randomised to angiography (n = 222), SPECT (n = 224), MRI (n = 226) or stress echo (n = 226). Initial diagnostic tests were completed successfully with unequivocal results for 98% of angiography, 94% of SPECT (p = 0.05), 78% of MRI (p < 0.001) and 90% of stress echocardiography patients (p < 0.001). Some 22% of SPECT patients, 20% of MRI patients and 25% of stress echo patients were not subsequently referred for an angiogram. Positive functional tests were confirmed by positive angiography in 83% of SPECT patients, 89% of MRI patients and 84% of stress echo patients. Negative functional tests were followed by positive angiograms in 31% of SPECT patients, 52% of MRI patients and 48% of stress echo patients tested. The proportions that had coronary artery bypass graft surgery were 10% (angiography), 11% (MRI) and 13% (SPECT and stress echo) and percutaneous coronary intervention 25% (angiography), 18% (SPECT) and 23% (MRI and stress echo). At 18 months, comparing SPECT and stress echo with angiography, a clinically significant difference in total exercise time can be ruled out. The MRI group had significantly shorter mean total exercise time of 35 seconds and the upper limit of the CI was 1.14 minutes less than in the angiography group, so a difference of at least 1 minute cannot be ruled out. At 6 months post-treatment, SPECT and angiography had equivalent mean exercise time. Compared with angiography, the MRI and stress echo groups had significantly shorter mean total exercise time of 37 and 38 seconds, respectively, and the upper limit of both CIs was 1.16 minutes, so a difference of at least 1 minute cannot be ruled out. The differences were mainly attributable to revascularised patients. There were significantly more non-fatal adverse events in the stress echo group, mostly admissions for chest pain, but no significant difference in the number of patients reporting events. Mean (95% CI) total additional costs over 18 months, compared with angiography, were 415 pounds (-310 pounds to 1084 pounds) for SPECT, 426 pounds (-247 pounds to 1088 pounds) for MRI and 821 pounds (10 pounds to 1715 pounds) for stress echocardiography, with very little difference in quality-adjusted life-years (QALYs) amongst the groups (less than 0.04 QALYs over 18 months). Cost-effectiveness was mainly influenced by test costs, clinicians' willingness to trust negative functional tests and by a small number of patients who had a particularly difficult clinical course. CONCLUSIONS: Between 20 and 25% of patients can avoid invasive testing using functional testing as a gateway to angiography, without substantial effects on outcomes. The SPECT strategy was as useful as angiography in identifying patients who should undergo revascularisation and the additional cost was not significant, in fact it would be reduced further by restricting the rest test to patients who have a positive stress test. MRI had the largest number of test failures and, in this study, had the least practical use in screening patients with suspected CAD, although it had similar outcomes to stress echo and is still an evolving technology. Stress echo patients had a 10% test failure rate, significantly shorter total exercise time and time to angina at 6 months post-treatment, and a greater number of adverse events, leading to significantly higher costs. Given the level of skill required for stress echo, it may be best to reserve this test for those who have a contraindication to SPECT and are unable or unwilling to have MRI. Further research, using blinded reassessment of functional test results and angiograms, is required to formally assess diagnostic accuracy. Longer-term cost-effectiveness analysis, and further studies of MRI and new generation computed tomography are also required.