Pharmaceutical policies: effects of regulating drug insurance schemes.

BACKGROUND: Drug insurance schemes are systems that provide access to medicines on a prepaid basis and could potentially improve access to essential medicines and reduce out-of-pocket payments for vulnerable populations. OBJECTIVES: To assess the effects on drug use, drug expenditure, healthcare utilisation and healthcare outcomes of alternative policies for regulating drug insurance schemes. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, nine other databases, and two trials registers between November 2014 and September 2020, including a citation search for included studies on 15 September 2021 using Web of Science. We screened reference lists of all the relevant reports that we retrieved and reports from the Background section. Authors of relevant papers, relevant organisations, and discussion lists were contacted to identify additional studies, including unpublished and ongoing studies. SELECTION CRITERIA: We planned to include randomised trials, non-randomised trials, interrupted time-series studies (including controlled ITS [CITS] and repeated measures [RM] studies), and controlled before-after (CBA) studies. Two review authors independently assessed the search results and reference lists of relevant reports, retrieved the full text of potentially relevant references and independently applied the inclusion criteria to those studies. We resolved disagreements by discussion, and when necessary by including a third review author. We excluded studies of the following pharmaceutical policies covered in other Cochrane Reviews: those that determined how decisions were made about which conditions or drugs were covered; those that placed restrictions on reimbursement for drugs that were covered; and those that regulated out-of-pocket payments for drugs. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included studies and assessed risk of bias for each study, with disagreements being resolved by consensus. We used the criteria suggested by  Cochrane Effective Practice and Organisation of Care (EPOC)  to assess the risk of bias of included studies. For randomised trials, non-randomised trials and controlled before-after studies, we planned to report relative effects. For dichotomous outcomes, we reported the risk ratio (RR) when possible and adjusted for baseline differences in the outcome measures. For interrupted time series and controlled interrupted time-series studies, we computed changes along two dimensions: change in level; and change in slope. We undertook a structured synthesis following the EPOC guidance on this topic, describing the range of effects found in the studies for each category of outcomes. MAIN RESULTS: We identified 58 studies that met the inclusion criteria (25 interrupted time-series studies and 33 controlled before-after studies). Most of the studies (54) assessed a single policy implemented in the United States (US) healthcare system: Medicare Part D. The other four assessed other drug insurance schemes from Canada and the US, but only one of them provided analysable data for inclusion in the quantitative synthesis. The introduction of drug insurance schemes may increase prescription drug use (low-certainty evidence). On the other hand, Medicare Part D may decrease drug expenditure measured as both out-of-pocket spending and total drug spending (low-certainty evidence). Regarding healthcare utilisation, drug insurance policies (such as Medicare Part D) may lead to a small increase in visits to the emergency department. However, it is uncertain whether this type of policy increases or decreases hospital admissions or outpatient visits by beneficiaries of the scheme because the certainty of the evidence was very low. Likewise, it is uncertain if the policy increases or reduces health outcomes such as mortality because the certainty of the evidence was very low. AUTHORS' CONCLUSIONS: The introduction of drug insurance schemes such as Medicare Part D in the US health system may increase prescription drug use and may decrease out-of-pocket payments by the beneficiaries of the scheme and total drug expenditures. It may also lead to a small increase in visits to the emergency department by the beneficiaries of the policy. Its effects on other healthcare utilisation outcomes and on health outcomes are uncertain because of the very low certainty of the evidence. The applicability of this evidence to settings outside US healthcare is limited.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.

BACKGROUND: Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium to longer term. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of foam, EVLA and surgery for the treatment of varicose veins. DESIGN: A parallel-group randomised controlled trial (RCT) without blinding, and economic modelling evaluation. SETTING: Eleven UK specialist vascular centres. PARTICIPANTS: Seven hundred and ninety-eight patients with primary varicose veins (foam, n = 292; surgery, n = 294; EVLA, n = 212). INTERVENTIONS: Patients were randomised between all three treatment options (eight centres) or between foam and surgery (three centres). PRIMARY OUTCOME MEASURES: Disease-specific [Aberdeen Varicose Vein Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D), Short Form questionnaire-36 items (SF-36) physical and mental component scores] quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality-adjusted life-year (QALY) gained. SECONDARY OUTCOME MEASURES: Quality of life at 6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS); complication rates; return to normal activity; truncal vein ablation rates; and costs. RESULTS: The results appear generalisable in that participants' baseline characteristics (apart from a lower-than-expected proportion of females) and post-treatment improvement in outcomes were comparable with those in other RCTs. The health gain achieved in the AVVQ with foam was significantly lower than with surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to -0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in SF-36 mental component score for foam was worse than that for EVLA (effect size 1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were no differences in EQ-5D or SF-36 component scores in the surgery versus foam or surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness analysis showed that, at 6 months, foam had the highest probability of being considered cost-effective at a ceiling willingness-to-pay ratio of £20,000 per QALY. EVLA was found to cost £26,107 per QALY gained versus foam, and was less costly and generated slightly more QALYs than surgery. Markov modelling using trial costs and the limited recurrence data available suggested that, at 5 years, EVLA had the highest probability (≈ 79%) of being cost-effective at conventional thresholds, followed by foam (≈ 17%) and surgery (≈ 5%). With regard to secondary outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to a wide range of behaviours more quickly following foam or EVLA than following surgery (p < 0.05). There were no differences in VCSS between the three treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA (p < 0.001) than for foam, and were similar for surgery and EVLA. CONCLUSIONS: Considerations of both the 6-month clinical outcomes and the estimated 5-year cost-effectiveness suggest that EVLA should be considered as the treatment of choice for suitable patients. FUTURE WORK: Five-year trial results are currently being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and to determine the recurrence rates following each treatment. This trial has highlighted the need for long-term outcome data from RCTs on QoL, recurrence rates and costs for foam sclerotherapy and other endovenous techniques compared against each other and against surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN51995477. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 27. See the NIHR Journals Library website for further project information.

Minimal access surgery compared with medical management for chronic gastro-oesophageal reflux disease: UK collaborative randomised trial.

OBJECTIVE: To determine the relative benefits and risks of laparoscopic fundoplication surgery as an alternative to long term drug treatment for chronic gastro-oesophageal reflux disease (GORD). DESIGN: Multicentre, pragmatic randomised trial (with parallel preference groups). SETTING: 21 hospitals in the United Kingdom. PARTICIPANTS: 357 randomised participants (178 surgical, 179 medical) and 453 preference participants (261, 192); mean age 46; 66% men. All participants had documented evidence of GORD and symptoms for >12 months. INTERVENTION: The type of laparoscopic fundoplication used was left to the discretion of the surgeon. Those allocated to medical treatment had their treatment reviewed and adjusted as necessary by a local gastroenterologist, and subsequent clinical management was at the discretion of the clinician responsible for care. MAIN OUTCOME MEASURES: The disease specific REFLUX quality of life score (primary outcome), SF-36, EQ-5D, and medication use, measured at time points equivalent to three and 12 months after surgery, and surgical complications. MAIN RESULTS: Randomised participants had received drugs for GORD for median of 32 months before trial entry. Baseline REFLUX scores were 63.6 (SD 24.1) and 66.8 (SD 24.5) in the surgical and medical randomised groups, respectively. Of those randomised to surgery, 111 (62%) actually had total or partial fundoplication. Surgical complications were uncommon with a conversion rate of 0.6% and no mortality. By 12 months, 38% (59/154) randomised to surgery (14% (14/104) among those who had fundoplication) were taking reflux medication versus 90% (147/164) randomised medical management. The REFLUX score favoured the randomised surgical group (14.0, 95% confidence interval 9.6 to 18.4; P<0.001). Differences of a third to half of 1 SD in other health status measures also favoured the randomised surgical group. Baseline scores in the preference for surgery group were the worst; by 12 months these were better than in the preference for medical treatment group. CONCLUSION: At least up to 12 months after surgery, laparoscopic fundoplication significantly increased measures of health status in patients with GORD. TRIAL REGISTRATION: ISRCTN15517081.

Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over: a randomised controlled trial.

BACKGROUND: Observational studies have frequently reported an association between cognitive function and nutrition in later life but randomised trials of B vitamins and antioxidant supplements have mostly found no beneficial effect. We examined the effect of daily supplementation with 11 vitamins and 5 minerals on cognitive function in older adults to assess the possibility that this could help to prevent cognitive decline. METHODS: The study was carried out as part of a randomised double blind placebo controlled trial of micronutrient supplementation based in six primary care health centres in North East Scotland. 910 men and women aged 65 years and over living in the community were recruited and randomised: 456 to active treatment and 454 to placebo. The active treatment consisted of a single tablet containing eleven vitamins and five minerals in amounts ranging from 50-210 % of the UK Reference Nutrient Intake or matching placebo tablet taken daily for 12 months. Digit span forward and verbal fluency tests, which assess immediate memory and executive functioning respectively, were conducted at the start and end of the intervention period. Risk of micronutrient deficiency at baseline was assessed by a simple risk questionnaire. RESULTS: For digit span forward there was no evidence of an effect of supplements in all participants or in sub-groups defined by age or risk of deficiency. For verbal fluency there was no evidence of a beneficial effect in the whole study population but there was weak evidence for a beneficial effect of supplementation in the two pre-specified subgroups: in those aged 75 years and over (n 290; mean difference between supplemented and placebo groups 2.8 (95% CI -0.6, 6.2) units) and in those at increased risk of micronutrient deficiency assessed by the risk questionnaire (n 260; mean difference between supplemented and placebo groups 2.5 (95% CI -1.0, 6.1) units). CONCLUSION: The results provide no evidence for a beneficial effect of daily multivitamin and multimineral supplements on these domains of cognitive function in community-living people over 65 years. However, the possibility of beneficial effects in older people and those at greater risk of nutritional deficiency deserves further attention.

Effect of multivitamin and multimineral supplements on morbidity from infections in older people (MAVIS trial): pragmatic, randomised, double blind, placebo controlled trial.

OBJECTIVE: To examine whether supplementation with multivitamins and multiminerals influences self reported days of infection, use of health services, and quality of life in people aged 65 or over. DESIGN: Randomised, placebo controlled trial, with blinding of participants, outcome assessors, and investigators. SETTING: Communities associated with six general practices in Grampian, Scotland. PARTICIPANTS: 910 men and women aged 65 or over who did not take vitamins or minerals. INTERVENTIONS: Daily multivitamin and multimineral supplementation or placebo for one year. MAIN OUTCOME MEASURES: Primary outcomes were contacts with primary care for infections, self reported days of infection, and quality of life. Secondary outcomes included antibiotic prescriptions, hospital admissions, adverse events, and compliance. RESULTS: Supplementation did not significantly affect contacts with primary care and days of infection per person (incidence rate ratio 0.96, 95% confidence interval 0.78 to 1.19 and 1.07, 0.90 to 1.27). Quality of life was not affected by supplementation. No statistically significant findings were found for secondary outcomes or subgroups. CONCLUSION: Routine multivitamin and multimineral supplementation of older people living at home does not affect self reported infection related morbidity. TRIAL REGISTRATION: ISRCTN: 66376460.