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:
A Practical Application of Value of Information and Prospective Payback of Research to Prioritize Evaluative Research
Abstract 1:
Background and Objectives . Efforts to ensure that funded research represents “ value for money ” have led to increasing calls for the use of analytic methods in research prioritization . A number of analytic approaches have been proposed to assist research funding decisions , the most prominent of which are value of information ( VOI ) and prospect i ve payback of research ( PPoR ) . Despite the increasing interest in the topic , there are insufficient VOI and PPoR applications on the same case study to contrast their methods and compare their outcomes . We undertook VOI and PPoR analyses to determine the value of conducting 2 proposed research programs . The application served as a vehicle for identifying differences and similarities between the methods , provided insight into the assumptions and practical requirements of undertaking prospect i ve analyses for research prioritization , and highlighted areas for future research . Methods . VOI and PPoR were applied to case studies representing proposals for clinical trials in advanced non-small-cell lung cancer and prostate cancer . Decision models were built to synthesize the evidence available prior to the funding decision . VOI ( expected value of perfect and sample information ) and PPoR ( PATHS model ) analyses were undertaken using the developed models . Results and Conclusions . VOI and PPoR results agreed in direction , suggesting that the proposed trials would be cost-effective investments . However , results differed in magnitude , largely due to the way each method conceptualizes the possible outcomes of further research and the implementation of research results in practice . Compared with VOI , PPoR is less complex but requires more assumptions . Although the approaches are not free from limitations , they can provide useful input for research funding decisions


Title 2:
Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010
Abstract 2:
BACKGROUND Measurement of the global burden of disease with disability-adjusted life-years ( DALYs ) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury . There has been extensive debate about a range of conceptual and method ological issues concerning the definition and measurement of these weights . Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new , st and ardised approach . METHODS We surveyed respondents in two ways : household surveys of adults aged 18 years or older ( face-to-face interviews in Bangladesh , Indonesia , Peru , and Tanzania ; telephone interviews in the USA ) between Oct 28 , 2009 , and June 23 , 2010 ; and an open-access web-based survey between July 26 , 2010 , and May 16 , 2011 . The surveys used paired comparison questions , in which respondents considered two hypothetical individuals with different , r and omly selected health states and indicated which person they regarded as healthier . The web survey added questions about population health equivalence , which compared the overall health benefits of different life-saving or disease-prevention programmes . We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study . We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 ( implying no loss of health ) to 1 ( implying a health loss equivalent to death ) . Additionally , we compared new disability weights with those used in WHO 's most recent up date of the Global Burden of Disease Study for 2004 . FINDINGS 13,902 individuals participated in household surveys and 16,328 in the web survey . Analysis of paired comparison responses indicated a high degree of consistency across surveys : correlations between individual survey results and results from analysis of the pooled data set were 0·9 or higher in all surveys except in Bangladesh ( r=0·75 ) . Most of the 220 disability weights were located on the mild end of the severity scale , with 58 ( 26 % ) having weights below 0·05 . Five ( 11 % ) states had weights below 0·01 , such as mild anaemia , mild hearing or vision loss , and secondary infertility . The health states with the highest disability weights were acute schizophrenia ( 0·76 ) and severe multiple sclerosis ( 0·71 ) . We identified a broad pattern of agreement between the old and new weights ( r=0·70 ) , particularly in the moderate-to-severe range . However , in the mild range below 0·2 , many states had significantly lower weights in our study than previously . INTERPRETATION This study represents the most extensive empirical effort as yet to measure disability weights . By contrast with the popular hypothesis that disability assessment s vary widely across sample s with different cultural environments , we have reported strong evidence of highly consistent results . FUNDING Bill & Melinda Gates Foundation


Title 3:
Analytic approaches for research priority-setting: issues, challenges and the way forward
Abstract 3:
In the last two decades , growing dem and for studies assessing healthcare interventions , coupled with the acknowledgment that limited public funds for research ought to be allocated efficiently , has led to increasing calls for the use of analytic approaches for research prioritization . Two main approaches have been proposed – ‘ value of information ’ and ‘ prospect i ve payback of research ’ – but neither of them is used formally in the prioritization process . This article discusses possible barriers to the formal adoption and use of analytic approaches . These include uncertainties around the appropriateness of using results of analytic approaches for priority- setting , questions around the validity of the results and challenges in introducing and using analytical methods as part of the prioritization process . It is argued that most of these challenges can be overcome and ways of doing so are discussed . The author ’s view on the direction and pace of future developments is provided , followed by recommendations for further research


Title 4:
Cost utility analysis of prophylactic pamidronate for the prevention of skeletal related events in patients with advanced breast cancer
Abstract 4:
Abstract Metastatic bone disease is a common complication of advanced breast cancer . Recently , the results of a large r and omized placebo-controlled trial demonstrated that monthly pamidronate infusions reduce the incidence of skeletal related events in these patients . In the current study , a cost – utility analysis was performed from a Canadian health care system perspective to estimate the incremental cost-effectiveness of pamidronate in patients with advanced breast cancer . Twenty-five advanced breast cancer patients who were bisphosphonate naïve and had developed skeletal related complications were identified .  Total hospital re source consumption was then collected for all patients . This included direct costs for hospitalization and costs for radiation treatment to bone , surgery , analgesics , blood products , diagnostic imaging , paramedical services and all related physician fees . Treatment preferences were estimated from a r and om sample of 25 women selected from the general population and 25 female health care professionals , using the Time Trade-Off technique . The outcomes were then generated through a decision-analytic model . Over a 12-month period , total costs in the pamidronate arm were approximately 44 % higher than those in the no-treatment alternative ( Can$ 9,180 vs Can$ 6,380 ) . When treatment preferences were incorporated into the analysis , the results of the decision model revealed an incremental pamidronate cost of $ 18,700 per quality -adjusted life year gained . The results of the sensitivity analysis suggested that this estimate was dependent on the cost of treating skeletal related events , particularly bone surgery . Even though pamidronate has a high drug acquisition cost , the results of the cost – utility analysis suggest that this agent does provide patients with a substantial quality -adjusted survival benefit at a reasonable cost to the Canadian health care system


Title 5:
Economic analysis of terminal care for patients with malignant osteolytic bone disease and pain treated with pamidronate
Abstract 5:
Abstract The goals of this study were the assessment ( 1 ) of all costs of terminal care of patients with osteolytic bone disease and pain and ( 2 ) of the economic consequences of the pamidronate treatment as observed in a prospect i ve clinical trial on the effectiveness of pamidronate . A total of 70 patients were recruited , who were all suffering from advanced tumour diseases ( 60 % breast cancer , 21 % multiple myeloma , and 19 % other tumours ) . In a single-institution study the patients were r and omly assigned to receive , in a double-blinded setting , pamidronate 60 mg i.v . or 90 mg i.v . every 3 weeks for a maximum of six cycles . Perception of pain intensity was recorded by self- assessment , using a linear analogue scale . Follow-up lasted 6 months after treatment . All elements of direct costs of in-patient and out-patient care were recorded in cooperation with the hospital administration and the health insurance companies [ Krankenkassen ] . Average monthly direct costs amounted to ECU 1,290 ( ±410 ) and 1,050 ( ±430 ) during the treatment phase and follow-up , respectively . Average in-patient costs were about three times the out-patient costs . Significantly higher costs ( by a factor of 2 ) were observed for terminal care in hospital ( last 3 months before death ) than for continued care ( of patients surviving the study period ) . The treatment with pamidronate  reduced pain significantly but did not add noticeably to the costs . The study showed that it is practicable and quite efficient to combine a pharmaco-economic evaluation with a clinical trial , although it may be difficult ( depending on the setting and availability of information ) to assess true costs , i.e. total re source usage


Title 6:
Cost-effectiveness of zoledronic acid for the prevention of skeletal complications in patients with prostate cancer.
Abstract 6:
PURPOSE We estimated the cost-effectiveness of zoledronic acid vs placebo for decreasing skeletal complications in men with prostate cancer . MATERIAL S AND METHODS We performed a cost-effectiveness analysis alongside a multinational clinical trial of zoledronic acid . Cost estimation was based on prospect ively collected re source use data for 85.3 % of enrolled patients . Cost-effectiveness ratios were based on within-trial data on clinical outcomes , quality of life and study medication cost . RESULTS Patients receiving zoledronic acid experienced fewer hospital days during a mean followup of 9 months ( average 5.6 vs 8.0 days ; p = 0.1910 ) . Mean direct costs excluding study medication were US dollars 5365 for patients receiving zoledronic acid and US dollars 5689 for patients receiving placebo , a difference of US dollars 324 ( 95 % CI US dollars 1781 to US dollars 1146 ) . The global average cost of zoledronic acid  plus its administration during the trial was US dollars 5677 ( US dollars 450 per dose ) . The nominal cost per skeletal complication avoided was US dollars 112300 ( 95 % CI US dollars 6900 to US dollars 48700 ) and the cost per additional patient free of skeletal complications was US dollars 51400 ( 95 % CI US dollars 26900 to US dollars 243700 ) . Nominal within-trial cost per quality adjusted life-year was US dollars 159200 , which varied widely in sensitivity analyses . CONCLUSIONS The nominal base case estimate of the cost per quality adjusted life-year for zoledronic acid in the prevention of skeletal complications of prostate cancer is consistent with that of bisphosphonates in breast cancer . However , the cost-effectiveness ratios for bisphosphonates are higher than commonly cited thresholds for conferring cost-effectiveness
Across types of cancer , evidence suggests that bisphosphonates result in lower morbidity and improved quality of life , for an additional cost , which is typically below conventional cost-effectiveness thresholds .
While denosumab leads to health gains compared with zoledronic acid , it also results in substantial additional costs and is unlikely to represent value for money .
The limited literature on the radiopharmaceutical strontium-89 ( Sr89 ) and external beam radiotherapy ( EBR ) suggest that these treatments are cost effective compared with no treatment .
Conclusions The review ed evidence suggests that bisphosphonate treatments are cost-effective options for bone metastases , while denosumab is unlikely to represent value for money .