***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 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 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 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 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 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 
    Output:
    
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 .