Monica Hernández

Percutaneous vertebroplasty and percutaneous balloon kyphoplasty for the treatment of osteoporotic vertebral fractures: a systematic review and cost-effectiveness analysis

BACKGROUNDnPercutaneous vertebroplasty (PVP) is a minimally invasive surgical procedure in which bone cement is injected into a fractured vertebra. Percutaneous balloon kyphoplasty (BKP) is a variation of this approach, in which an inflatable balloon tamp is placed in the collapsed vertebra prior to cement injection.nnnOBJECTIVESnTo systematically evaluate and appraise the clinical effectiveness and cost-effectiveness of PVP and percutaneous BKP in reducing pain and disability in people with osteoporotic vertebral compression fractures (VCFs) in England and Wales.nnnDATA SOURCESnA systematic review was carried out. Ten databases including MEDLINE and CINAHL were searched from inception to November 2011, and supplemented by hand-searching relevant articles and contact with an expert. Studies met the inclusion criteria if they were randomised controlled trials (RCTs) including people with painful osteoporotic VCFs with a group receiving PVP or BKP. In addition, lead authors of identified RCTs were contacted for unpublished data.nnnREVIEW METHODSnPrimary outcomes were health-related quality of life; back-specific functional status/mobility; pain/analgesic use; vertebral body height and angular deformity; incidence of new vertebral fractures and progression of treated fracture. A manufacturer provided academic-in-confidence observational data indicating that vertebral augmentation may be associated with a beneficial mortality effect, and that, potentially, BKP was more efficacious than PVP. These data were formally critiqued. A mathematical model was constructed to explore the cost-effectiveness of BKP, PVP and operative placebo with local anaesthesia (OPLA) compared with optimal pain management (OPM). Six scenario analyses were conducted that assessed combinations of assumptions on mortality (differential beneficial effects for BKP and PVP; equal beneficial effects for BKP and PVP; and no effect assumed) and derivation of utility data (either mapped from visual analogue scale pain score data produced by a network meta-analysis or using direct European Quality of Life-5 Dimensions data from the trials). Extensive sensitivity analyses were conducted on each of the six scenarios. This report contains reference to confidential information provided as part of the National Institute for Health and Care Excellence appraisal process. This information has been removed from the report and the results, discussions and conclusions of the report do not include the confidential information. These sections are clearly marked in the report.nnnRESULTSnA total of nine RCTs were identified and included in the review of clinical effectiveness. This body of literature was of variable quality, with the two double-blind, OPLA-controlled trials being at the least risk of bias. The most significant methodological issue among the remaining trials was lack of blinding for both study participants and outcome assessors. Broadly speaking, the literature suggests that both PVP and BKP provide substantially greater benefits than OPM in open-label trials. However, in double-blinded trials PVP was shown to have no more benefit than local anaesthetic; no trials of BKP compared with local anaesthesia have been conducted. A formal analysis of observational mortality data undertaken within this report concluded that it was not possible to say with certainty if there is a difference in mortality between patients undergoing BKP and PVP compared with OPM. Results from the cost-effectiveness analyses were varied, with all of BKP, PVP and OPLA appearing the most cost-effective treatment dependent on the assumptions made regarding mortality effects, utility, hospitalisation costs and OPLA costs.nnnLIMITATIONSnData on key parameters were uncertain and/or potentially confounded, making definitive conclusions difficult to make.nnnCONCLUSIONnFor people with painful osteoporotic VCFs refractory to analgesic treatment, PVP and BKP perform significantly better in unblinded trials than OPM in terms of improving quality of life and reducing pain and disability. However, there is as yet no convincing evidence that either procedure performs better than OPLA. The uncertainty in the evidence base means that no definitive conclusion on the cost-effectiveness of PVP or BKP can be provided. Further research should focus on establishing whether or not BKP and PVP have a mortality advantage compared with OPLA and on whether or not these provide any utility gain compared with OPLA.nnnSTUDY REGISTRATIONnThis study was registered as PROSPERO number CRD42011001822.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review.

BACKGROUNDnObesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise.nnnOBJECTIVEnTo evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients.nnnDATA SOURCESnClinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature.nnnREVIEW METHODSnA systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin.nnnRESULTSnOverall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY.nnnLIMITATIONSnThe clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses.nnnCONCLUSIONnThe MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

Modeling Health State Utility Values in Ankylosing Spondylitis: Comparisons of Direct and Indirect Methods

OBJECTIVESnCost-effectiveness analyses of technologies for patients with ankylosing spondylitis frequently require estimates of health utilities as a function of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI).nnnMETHODSnLinear regression, bespoke mixture models, and generalized ordered probit models were used to model the EuroQol five-dimensional questionnaire as a function of BASDAI and BASFI. Data were drawn from a large UK cohort study (n = 516 with up to five observations) spanning the full range of disease severity.nnnRESULTSnLinear regression was systematically biased. Three- and four-component mixture models and generalized probit models exhibit no such bias and improved fit to the data. The mean, median, mean error, and mean absolute error favored the mixture model approach. Root mean square error favored the generalized ordered probit model approach for the data as a whole. Model fit assessed using these same measures by disease severity quartiles tended to be best using the mixture models. The value of moving from good to poor health may differ substantially according to the chosen method. Simulated data from the mixture and probit models yield a very similar distribution to the original data set.nnnCONCLUSIONSnThese results add to a body of evidence that the statistical model used to estimate health utilities matters. Linear models are not appropriate. The four-class bespoke mixture model approach provides the best performing method to estimate the EuroQol five-dimensional questionnaire values from BASDAI and BASFI.

Health State Preference Weights for the Glasgow Outcome Scale Following Traumatic Brain Injury: A Systematic Review and Mapping Study

Background Valid and relevant estimates of health state preference weights (HSPWs) for Glasgow Outcome Scale (GOS) categories are a key input of economic models evaluating treatments for traumatic brain injury (TBI). Objectives To characterize existing HSPW estimates, and model the EuroQol five-dimensional questionnaire (EQ-5D) from the GOS, to inform parameterization of future economic models. Methods A systematic review of HSPWs for GOS categories following TBI was conducted using a highly sensitive search strategy implemented in an extensive range of information sources between 1975 and 2016. A cross-sectional mapping study of GOS health states onto the three-level EQ-5D UK tariff index values was also performed in patients with significant TBI (head region Abbreviated Injury Scale score ≥3) from the Victoria State Trauma Registry. A limited dependent variable mixture model was used to estimate the 12-month EQ-5D UK value set as a function of GOS category, age, and other explanatory variables. Results Six unique HSPWs from five eligible studies were identified. All studies were at high risk of bias with limited applicability. The magnitude of HSPWs differed significantly between studies. Three class mixture models demonstrated excellent goodness of fit to the observed Victoria State Trauma Registry data. GOS category, age at injury, sex, comorbidity, and major extracranial injury all had significant independent effects on mean EQ-5D utility values. Conclusions The few available HSPWs for GOS categories are challenged by potential biases and restricted generalizability. Mixture models are presented to provide HSPWs for GOS categories consistent with the National Institute for Health and Care Excellence reference case.