You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Development and Validation of a Grading System for the Quality of Cost-Effectiveness Studies
Abstract 1:
Purpose .To provide a practical quantitative tool for appraising the quality of  cost-effectiveness ( CE ) studies . Methods .A committee comprised of health economists selected a set of criteria for the instrument from an item pool . Data collected with a conjoint analysis survey on 120 international health economists were used to estimate weights for each criterion with a r and om effects regression model . To vali date the grading system , a survey was sent to 60 individuals with health economics expertise . Participants first rated the quality  of three CE studies  on a visual analogue scale , and then evaluated each study using the  grading system . Spearman rho and Wilcoxon tests were used to detect convergent validity and analysis of covariance ( ANCOVA ) for discriminant validity . Agreement between the global rating by experts and the grading system was also examined . Results .Sixteen criteria were selected . Their coefficient estimates ranged from 1.2 to 8.9 , with a sum of 93.5 on a 100-point scale . The only insignificant criterion was “ use of subgroup analyses . ” Both convergent validity and discriminant validity of the grading system were shown by the results of the Spearman rho ( correlation coefficient = 0.78 , P < 0.0001 ) , Wilcoxon test ( P = 0.53 ) , and ANCOVA ( F3,146 = 5.97 , P = 0.001 ) . The grading system had good agreement with global rating by experts . Conclusions . The instrument appears to be simple , internally consistent , and valid for measuring the perceived quality of CE studies . Applicability for use in clinical and re source allocation decision-making deserves further study


Title 2:
Cost effectiveness of bortezomib in the treatment of advanced multiple myeloma.
Abstract 2:
This study evaluated the cost effectiveness of  bortezomib  in relapsed , refractory myeloma , relative to best supportive care ( BSC ) and thalidomide . Data were derived from the phase 2 pivotal study of bortezomib  , a Delphi panel of six myeloma thought leaders , and published literature . Objective assumptions regarding treatment choices and consequences ( response and complications ) , and actual cost data were used . Bortezomib was found to be cost effective relative to BSC and thalidomide . Sensitivity analyses demonstrated the robustness of the results . These data suggest that bortezomib provides a cost-effective treatment option and the best value ( in terms of cost/life-yr gained ) among the currently available therapeutic options for relapsed , refractory myeloma


Title 3:
Pharmacoeconomic Implications of Lenalidomide Maintenance Therapy in Multiple Myeloma
Abstract 3:
We compared the three arms of the MM-015 r and omized phase III clinical trial [ melphalan and prednisone ( MP ) , MP plus lenalidomide ( MPR ) , and MPR plus lenalidomide maintenance ( MPR-R ) ] to determine whether the addition of lenalidomide maintenance therapy for primary treatment of multiple myeloma is cost-effective . We used progression-free survival and adverse event data from the MM-015 study for the analysis . Two novel measures of cost-effectiveness termed the Average Cumulative Cost per Patient ( ACCP ) and the Average Cumulative Cost per Progression-Free Survivor ( ACCPFS ) were developed for the purpose of this analysis . The ACCP of MP was USD 18,218 , compared to USD 167,862 for MPR and USD 309,173 for MPR-R. The ACCPFS was highest with MPR at USD 1,555,443 , while MP was USD 313,592 and MPR-R was USD 690,111 . MPR-R is superior to MPR in terms of preventing the first progression after initial therapy . However , the addition of lenalidomide to MP in the induction and also in the maintenance setting leads to significant costs


Title 4:
Cost-effectiveness of a Transplantation Strategy Compared to Melphalan and Prednisone in Younger Patients with Multiple Myeloma
Abstract 4:
High dose chemotherapy with autologous stem cell transplantation ( ASCT ) improves outcomes in patients 65 years of age or less with multiple myeloma .  Survival and costs in a cohort of 16 patients who received melphalan and prednisone as part of a clinical trial were compared with those of 36 patients referred to our centre for consideration of ASCT . In the transplant group , survival and costs were extrapolated to match the period of observation in the melphalan and prednisone group . Patient-specific and average costs were calculated from the perspective of the Ontario Ministry of Health . Costs and survival were varied by 50 % in the sensitivity analysis . Transplantation improved life expectancy by 19.3 months with a cost difference of $ 30,517 Canadian . The incremental cost-effectiveness of transplantation compared with melphalan and prednisone was $ 25,710 Canadian per life-year gained when additional pamidronate and follow-up costs were considered . Discounting costs and survival at 3 and 5 % did not result in important differences . The sensitivity analysis result ed in best and worse case scenarios for transplantation compared with melphalan and prednisone of $ 13,049 and $ 63,954 per life-year gained respectively . In comparison with melphalan and prednisone , ASCT appears to be cost-effective in patients 65 years old or younger with myeloma


Title 5:
The cost-effectiveness of initial treatment of multiple myeloma in the U.S. with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment.
Abstract 5:
The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into st and ard regimens . Novel regimens combine melphalan and prednisone ( MP ) with bortezomib ( VMP ) , with thalidomide ( MPT ) , and with lenalidomide with ( MPR-R ) and without ( MPR ) lenalidomide maintenance . The efficacy , safety , and cost-effectiveness of these regimens have not yet been compared ; therefore , we conducted a pharmacoeconomic analysis using data from r and omized controlled trials versus MP . Using a Markov model developed from a U.S. payer 's perspective , we compared VMP with MPT and MPR-R over a lifetime horizon . MPT and MPR-R were chosen because , like VMP , they are superior to MP in response and outcomes . Data from the Velcade as Initial St and ard Therapy in Multiple Myeloma ( VISTA ; VMP ) , Intergroupe Francophone du Myelome ( IFM ) 99 - 06 ( MPT ) , and MM-015 ( MPR-R ) trials were used . The IFM 99 - 06 study was selected because of the superior activity in this study compared with other MPT studies . Using patient-level ( VMP ) and published ( MPT , MPR-R ) data , we estimated the health-state transition and adverse event probabilities for each regimen , related costs , and state-specific utility estimates . Costs ( in 2010 U.S. dollars ) and health outcomes were discounted at 3 % . Discounted lifetime direct medical costs were lowest with VMP at $ 119,102 . MPT cost $ 142,452 whereas MPR-R cost $ 248,358 . Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP , MPT , and
For transplant-eligible MM patients , transplant is a cost-effective first-line treatment .
In the second-line setting , it is unclear which novel agent-based regimen is most cost effective , but bortezomib-based regimens , lenalidomide plus dexamethasone , and pomalidomide plus dexamethasone were each cost effective compared with dexamethasone alone