Bruce Crawford

Bayesian Meta-Analysis of Multiple Treatment Comparisons: An Introduction to Mixed Treatment Comparisons

Recently, mixed treatment comparisons (MTC) have been presented as an extension of traditional meta-analysis by including multiple different pairwise comparisons across a range of different interventions. MTC allow for indirect comparisons and can therefore provide very useful information for clinical and reimbursement decision-making in the absence of head-to-head data. In this article, we provide an introductory overview of MTC illustrated with example analyses of different drug treatments in rheumatoid arthritis using a continuous patient-reported end point. As a background, we start with an overview of the traditional meta-analyses for pairwise trials, and the difference between a traditional approach and a Bayesian approach. Next, the Bayesian MTC for continuous outcomes are presented. We finish with a discussion of how MTC can best be presented in order to maximize acceptance by target audiences, i.e., clinicians and market access decision-makers.

Improvement in health-related quality of life in patients with SLE following sustained reductions in anti-dsDNA antibodies.

Patients with systemic lupus erythematosus experience a decreased health-related quality of life due to disease activity, multisystem organ involvement and frequent hospitalization. High levels of anti-double-stranded DNA antibodies are associated with renal disease, a primary cause of morbidity and mortality in systemic lupus erythematosus, and progressive cognitive dysfunction. Post hoc analyses of two clinical trials of abetimus sodium identified responders with sustained reductions in anti-double-stranded DNA antibodies. At 6 and 12 months, responders reported improvement in health-related quality of life, as measured by the Medical Outcomes Survey Short Form 36, compared with no change or deterioration in nonresponders. Sustained reductions in anti-double-stranded DNA antibodies, regardless of treatment group, led to clinically meaningful improvements in patient-reported health-related quality of life.

Comparative efficacy and safety of novel oral anticoagulants in patients with atrial fibrillation: A network meta-analysis with the adjustment for the possible bias from open label studies

BACKGROUND This study was designed to compare efficacy and safety among novel oral anticoagulants (NOACs), which have not been directly compared in randomized control trials to date. METHOD We performed network meta-analyses of randomized control trials in preventing thromboembolic events and major bleeding in patients with atrial fibrillation. PubMed, Embase, and the Cochrane Database of Systematic Reviews for published studies and various registries of clinical trials for unpublished studies were searched for 2002-2013. All phase III randomized controlled trials (RCTs) of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), idraparinux, and ximelagatran were reviewed. RESULTS A systematic literature search identified nine phase III RCTs for primary analyses. The efficacy of each NOAC was similar with respect to our primary composite endpoint following adjustment for open label designs [odds ratios (ORs) versus vitamin K antagonists: apixaban 0.79; dabigatran 150mg 0.77; edoxaban 60mg 0.87; rivaroxaban 0.86] except for dabigatran 110mg and edoxaban 30mg. Apixaban and edoxaban 30mg and 60mg had significantly fewer major bleeding events than dabigatran 150mg, ricvaroxaban, and vitamin K antagonists. All NOACs were similar in reducing secondary endpoints with the exception of dabigatran 110mg and 150mg which were associated with a significantly greater incidence of myocardial infarction compared to apixaban, edoxaban 60mg, and rivaroxaban. CONCLUSIONS Our indirect comparison with adjustment for study design suggests that the efficacy of the examined NOACs is similar across drugs, but that some differences in safety and risk of myocardial infarction exist, and that open label study designs appear to overestimate safety and treatment efficacy. Differences in study design should be taken into account in the interpretation of results from RCTs of NOACs.

Evaluation of the willingness-to-pay for cancer treatment in Korean metastatic breast cancer patients: A multicenter, cross-sectional study

Aims:  To evaluate the inherent value of breast cancer therapy a willingness‐to‐pay (WTP) study was conducted in Korean patients with metastatic breast cancer.

Optimal Treatment for Complicated Intra-abdominal Infections in the Era of Antibiotic Resistance: A Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Therapy With Metronidazole

A meta-analysis of 8 clinical trials revealed that combined therapy with metronidazole is as effective and safe as carbapenem monotherapy in treating cIAIs. With a rise of Carbapenem-resistant Enterobacteriaceae, combined therapy with metronidazole can be an alternative therapy for cIAIs.

Meeting the US FDA's evidence standard with health-related quality of life claims.

Bruce Crawford, MA, MPH Senior Project Director / Manager US Operations, Mapi Values, 15 Court Square, Suite 620, Boston, MA 02108, USA Tel: +1 617 720 0001 Fax: +1 617 720 0004 bruce.crawford@mapivaluesusa.com Laurie Burke, RPh, MPH Director, Study Endpoints and Label Development, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, 5600 Fishers Lane HFD-020, Rockville, MD 20857, USA Tel.: +1 301 594 3937 Fax: +1 301 827 0486 BURKEL@cder.fda.gov

Economic Impact of Venous Thromboembolism Following Major Orthopaedic Surgery in Japan

OBJECTIVES Venous thromboembolism (VTE) is the most frequent complication following major orthopaedic surgery (MOS). Although studies in Western populations have demonstrated significantly higher costs for patients with VTE versus those without VTE after MOS, there is a paucity of such data in Japan. This study was conducted to understand the costs and VTE rates in Japanese patients. METHODS Data were extracted from a hospital claims database. MOS was defined as total hip replacement, total knee replacement, or hip fracture repair. Subjects who underwent more than one MOS during the same admission were excluded. Identified VTE cases were matched on a 1:2 matching scheme on the basis of surgery type, hospital, and date of surgery (±6 months). The primary outcome was the difference in 90-day costs. Secondary outcomes included differences in total 6-month costs postsurgery and average length and cost of initial hospital stay. RESULTS The 90-day cumulative VTE incidence was 0.774%, with 94% of the cases occurring within 30 days postsurgery. Total 90-day costs were significantly higher in patients with VTE (difference of 864,153 Japanese yen [US

Hepatitis C virus in Asia: utility values based on the Short Form-36 questionnaire.

10,538]). Average length of stay was longer for patients with VTE (66 days vs. 42 days). Costs incurred by patients with VTE were on average much higher than those incurred by patients without VTE throughout 5 months postsurgery. CONCLUSIONS The development of a VTE in patients undergoing MOS results in a 1.5-fold increase in the length of stay and a 1.7-fold increase in 90-day costs. Findings indicate that the avoidance of VTEs through more effective prophylaxis will help to reduce the economic burden associated with MOS.

Neuropathic pain: A patient-centred approach to measuring outcomes

Utility data are important in Asia, where the need for health economic evaluations is growing. A literature review was conducted across international and local bibliographical databases in four languages to evaluate the utilities for chronic hepatitis C (CHC) patients in Asia. The results showed a lack of research on the humanistic burden of CHC in Asia. Using mapping, the estimated utilities for CHC patients in Asia ranged between 0.68 and 0.86. The utilities of CHC patients were lower than that of healthy controls, with the differences ranging between 0.032 and 0.261 units. On-treatment utility values declined by 0.07–0.13 units for subjects without sustained virological response and by 0.03–0.06 units for sustained virological response subjects. The results provide empirical data on utility values among CHC patients in Asia that can be used in future cost–effectiveness analysis or health technology assessment.

Economic Burden of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery

Neuropathic pain (NP) is a complex, chronic pain state initiated by a primary lesion or dysfunction of the nervous system and presents as a variety of symptoms across multiple disease states.