BackgroundNetwork meta-analysis (NMA) allows for the estimation of comparative effectiveness of treatments that have not been studied in head-to-head trials; however, relative treatment effects for all interventions can only be derived where available evidence forms a connected network. Head-to-head evidence is limited in many disease areas, regularly resulting in disconnected evidence structures where a large number of treatments are available. This is also the case in the evidence of treatments for relapsed or refractory multiple myeloma.MethodsRandomised controlled trials (RCTs) identified in a systematic literature review form two disconnected evidence networks. Standard Bayesian NMA models are fitted to obtain estimates of relative effects within each network. Observational evidence was identified to fill the evidence gap. Single armed trials are matched to act as each other’s control group based on a distance metric derived from covariate information. Uncertainty resulting from including this evidence is incorporated by analysing the space of possible matches.ResultsTwenty five randomised controlled trials form two disconnected evidence networks; 12 single armed observational studies are considered for bridging between the networks. Five matches are selected to bridge between the networks. While significant variation in the ranking is observed, daratumumab in combination with dexamethasone and either lenalidomide or bortezomib, as well as triple therapy of carfilzomib, ixazomib and elozumatab, in combination with lenalidomide and dexamethasone, show the highest effects on progression free survival, on average.ConclusionsThe analysis shows how observational data can be used to fill gaps in the existing networks of RCT evidence; allowing for the indirect comparison of a large number of treatments, which could not be compared otherwise. Additional uncertainty is accounted for by scenario analyses reducing the risk of over confidence in interpretation of results.Electronic supplementary materialThe online version of this article (10.1186/s12874-018-0509-7) contains supplementary material, which is available to authorized users.

Aims This analysis aims to estimate the comparative efficacy of anti-hypertensive medications and exercise interventions on systolic and diastolic blood pressure reduction in people with hypertension. Methods A systematic review was conducted focusing on randomised controlled trials (RCTs) of exercise interventions and first-line anti-hypertensives where blood pressure reduction was the primary outcome in those with hypertension. Network meta-analyses were conducted to generate estimates of comparative efficacy. Results We identified 93 RCTs ( N = 32,404, mean age in RCTs: 39–70 years) which compared placebo or usual care with first-line antihypertensives including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers and thiazide-like diuretics and exercise interventions including aerobic training and dynamic resistance training. Of these, there were 81 (87%) trials related to medications ( n = 31,347, 97%) and 12 (13%) trials related to exercise ( n = 1057, 3%). The point estimates suggested that antihypertensive medications were more effective than exercise but there was insufficient evidence to suggest that first-line medications significantly reduced blood pressure to a greater extent than did the exercise interventions. Of the first-line treatments, angiotensin receptor blockers and calcium channel blockers had the highest treatment ranking, while exercise had the second lowest treatment ranking, followed by control conditions. Conclusion The current evidence base with a bias towards medication research may partly explain the circumspection around the efficacy of exercise in guidelines and practice. Clinicians may justifiably consider exercise for low risk hypertension patients who confirm a preference for such an approach.

Objectives This study evaluates the cost-effectiveness of tisagenlecleucel (a CAR T-cell therapy), versus blinatumomab, for the treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in the Irish healthcare setting. The value of conducting further research, to investigate the value of uncertainty associated with the decision problem, is assessed by means of expected value of perfect information (EVPI) and partial EVPI (EVPPI) analyses. Methods A three-state partitioned survival model was developed. A short-term decision tree partitioned patients in the tisagenlecleucel arm according to infusion status. Survival was extrapolated to 60 months; general population mortality with a standardized mortality ratio was then applied. Estimated EVPI and EVPPI were scaled up to population according to the incidence of the decision. Results At list prices, the incremental cost-effectiveness ratio was EUR 73,086 per quality-adjusted life year (QALY) (incremental costs EUR 156,928; incremental QALYs 2.15). The probability of cost-effectiveness, at the willingness-to-pay threshold of EUR 45,000 per QALY, was 16 percent. At this threshold, population EVPI was EUR 314,455; population EVPPI was below EUR 100,000 for each parameter category. Conclusions Tisagenlecleucel is not cost effective, versus blinatumomab, for the treatment of pediatric and young adult patients with R/R ALL in Ireland (at list prices). Further research to decrease decision (parameter) uncertainty, at the defined willingness-to-pay threshold, may not be of value. However, there is a high degree of uncertainty underpinning the analysis, which may not be captured by EVPI analysis.

It is expected that the coronavirus disease 2019 (COVID-19) pandemic will leave large deficits in the budgets of many jurisdictions. Funding for other treatments, in particular new treatments, may become more constrained than previously expected. Therefore, a robust health technology assessment (HTA) system is vital. Many clinical trials carried out during the pandemic may have been temporarily halted, while others may have had to change their protocols. Even trials that continue as normal may experience external changes as other aspects of the healthcare service may not be available to the patients in the trial, or the patients themselves may contract COVID-19. Consequently, many limitations are likely to arise in the provision of robust HTAs, which could have profound consequences on the availability of new treatments. Therefore, the National Centre for Pharmacoeconomics Review Group wishes to discuss these issues and make recommendations for applicants submitting to HTA agencies, in ample time for these HTAs to be prepared and assessed. We discuss how the pandemic may affect the estimation of the treatment effect, costs, life-years, utilities, discontinuation rates, and methods of evidence synthesis and extrapolation. In particular, we note that trials conducted during the pandemic will be subject to a higher degree of uncertainty than before. It is vital that applicants clearly identify any parameters that may be affected by the pandemic. These parameters will require considerably more scenario and sensitivity analyses to account for this increase in uncertainty.