Net clinical benefit of antiplatelet therapy was affected by patient preferences:A personalized benefit-risk assessment

Objectives: To assess the effect of patient preferences on the net clinical benefit (NCB) of an antiplatelet therapy for the secondary prevention of cardiovascular complications. Study Design and Setting: Risk equations were developed to estimate the individual predicted risk of key outcomes of antiplatelet treatment in patients with a prior myocardial infarction using the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and UK Office of National Statistics databases. Patient preferences for outcomes of antiplatelet therapies were elicited in a separate discrete choice experiment survey. Trial hazard ratios, relative to placebo, were used to calculate the per-patient NCB using equal or preference weighting of outcomes. Results: Risk equations were estimated using 31,941 adults in the Clinical Practice Research Datalink population, of which 22,125 were included in the benefit-risk assessment. The mean NCB was lower in the preference-weighted than in the equal-weighted analysis (0.040 vs. 0.057; P < 0.0001), but the direction of effect was unchanged by the weighting. In analyses stratified by the presence of bleeding risk factors, including preference weighting altered the ranking of subgroups by NCB. Conclusion: Patient preference weighting may have a significant effect on NCB and should be included in personalized benefit-risk assessments

Ponatinib vs. Imatinib as Frontline Treatment for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia : A Matching Adjusted Indirect Comparison

Introduction: Efficacy of ponatinib-based treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) has not been compared to imatinib-based treatments in head-to-head clinical trials. We evaluated its efficacy versus imatinib-based regimens using a matching adjusted indirect comparison. Methods: Two ponatinib studies were used: the phase 2 MDACC study of ponatinib + hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone) in adult patients and the phase 2 GIMEMA LAL1811 study of ponatinib + steroids in patients > 60 years/unfit for intensive chemotherapy and stem cell transplant. Studies on imatinib as first-line treatment in adults with Ph + ALL were identified using a systematic literature search. Population adjustment was based on the prognostic factors and effect modifiers identified by clinical experts. Hazard ratios (HRs) were calculated for overall survival (OS) and odds ratios (ORs) for complete molecular response (CMR). Results: The systematic literature search identified two studies (GRAAPH-2005 and NCT00038610) reporting the efficacy of first-line imatinib + hyper-CVAD and one study reporting the efficacy of first-line imatinib monotherapy induction + imatinib-based consolidation (CSI57ADE10). Ponatinib + hyper-CVAD prolonged OS and gave a higher CMR rate than imatinib + hyper-CVAD. The adjusted HR [95% confidence interval (CI)] for OS was 0.35 (0.17-0.74) for MDACC vs. GRAAPH-2005 and 0.35 (0.18-0.70) for MDACC vs. NCT00038610; the adjusted OR (95% CI) for CMR was 12.11 (3.77-38.87) for MDACC vs. GRAAPH-2005 and 5.65 (2.02-15.76) for MDACC vs. NCT00038610. Ponatinib + steroids prolonged OS and gave a higher CMR rate than imatinib monotherapy induction + imatinib-containing consolidation. The adjusted HR (95% CI) for OS was 0.24 (0.09-0.64) and the adjusted OR (95% CI) for CMR was 6.20 (1.60-24.00) for GIMEMA LAL1811 vs. CSI57ADE10. Conclusion: In adults with newly diagnosed Ph + ALL, first-line treatment with ponatinib was associated with better outcomes than first-line treatment with imatinib