How are health technology assessment bodies responding to the assessment challenges posed by cell and gene therapy?

BACKGROUND: The aims of this research were to provide a better understanding of the specific evidence needs for assessment of clinical and cost-effectiveness of cell and gene therapies, and to explore the extent that the relevant categories of evidence are considered in health technology assessment (HTA) processes. METHODS: A targeted literature review was conducted to identify the specific categories of evidence relevant to the assessment of these therapies. Forty-six HTA reports for 9 products in 10 cell and gene therapy indications across 8 jurisdictions were analysed to determine the extent to which various items of evidence were considered. RESULTS: The items to which the HTA bodies reacted positively were: treatment was for a rare disease or serious condition, lack of alternative therapies, evidence indicating substantial health gains, and when alternative payment models could be agreed. The items to which they reacted negatively were: use of unvalidated surrogate endpoints, single arm trials without an adequately matched alternative therapy, inadequate reporting of adverse consequences and risks, short length of follow-up in clinical trials, extrapolating to long-term outcomes, and uncertainty around the economic estimates. CONCLUSIONS: The consideration by HTA bodies of evidence relating to the particular features of cell and gene therapies is variable. Several suggestions are made for addressing the assessment challenges posed by these therapies. Jurisdictions conducting HTAs of these therapies can consider whether these suggestions could be incorporated within their existing approach through strengthening deliberative decision-making or performing additional analyses.

Cost comparison of insulin glargine with insulin detemir in a basal-bolus regime with mealtime insulin aspart in type 2 diabetes in Germany.

OBJECTIVE: To compare the treatment costs of insulin glargine (IG; Lantus) to detemir (ID; Levemir), both combined with bolus insulin aspart (NovoRapid) in type 2 diabetes (T2D) in Germany. METHODS: Cost comparison was based on data of a 1-year randomised controlled trial. IG was administered once daily and ID once (57% of patients) or twice daily (43%) according to treatment response. At the end of the trial, mean daily basal insulin doses were 0.59 U/kg (IG) and 0.82 U/kg (ID). Aspart doses were 0.32 U/kg (IG) and 0.36 U/kg (ID). Costs were calculated from the German statutory health insurance (SHI) perspective using official 2008 prices. Sensitivity analyses were performed to test robustness of the results. RESULTS: Annual basal and bolus insulin costs per patient were euro 1,473 (IG) and euro 1,940 (ID). The cost of lancets and blood glucose test strips were euro 1,125 (IG) and euro 1,286 (ID). Annual costs for needles were euro 393 (IG) and euro 449 (ID). The total annual cost per patient of administering IG was euro 2,991 compared with euro 3,675 for ID, translating into a 19% annual cost difference of euro 684/patient. Base case results were robust to varying assumptions for insulin dose, insulin price, change in weight and proportion of ID once daily administrations. CONCLUSION: IG and ID basal-bolus regimes have comparative safety and efficacy, based on the Hollander study, IG however may represent a significantly more cost saving option for T2D patients in Germany requiring basal-bolus insulin analogue therapy with potential annual cost savings of euro 684/patient compared to ID.

Effects of the Statutory Health Insurance Modernization Act on the supply and expenditure situation in cases of assisted reproductive technologies in Germany.

In the present retrospective analysis of outpatient health insurance members of the Statutory Health Insurance (SHI) in total and a subgroup of the Techniker Krankenkasse (TK), the effect of the commencement of the SHI Modernization Act (so-called GMG) on the supply and expenditure situation regarding assisted reproductive technologies (ART) in Germany was examined. The implementation of the GMG in Germany in 2004 resulted in a conspicuous decrease of infertility treatments (from 2002-2005 by approximately 60% in the whole SHI population, and by 55% in the TK) for couples with involuntary childlessness, whereby the extremely raised compulsory copayments to the insurance benefits were identified as the determining factor.

Effects of the National Institute for Health and Clinical Excellence's technology appraisals on prescribing and net ingredient costs of drugs in the National Health Service in England.

OBJECTIVES: The aim of this study was to examine the impact of the National Institute for Health and Clinical Excellence's (NICE's) negative and restricting technology appraisals on the number of prescription items dispensed and the corresponding total net ingredient costs for drugs from 2000 to 2004 in the ambulatory care of the National Health Service (NHS) in England and Wales. In addition, it is discussed whether the NICE approach could be a role model for Germany. METHODS: The number of prescription items dispensed and the net ingredient costs of thirty-one drugs reimbursed by the NHS were analyzed, thereof thirteen drugs descriptively and twenty-one drugs with regression analyses. Data were extracted from the "Prescription-Costs-Analysis-Statistics" for the ambulatory care of the British Department of Health (England 1993-2005). In the case of the twenty-one drugs analyzed by regression analyses, predictions were established how the prescribing and the costs would have developed without NICE's drug appraisal. Finally, conclusions were drawn whether NICE's negative and restricting drug appraisals had a decreasing effect or not. RESULTS: For 97 percent of the drugs analyzed in this study, the publication of NICE's fourteen negative and restricting technology appraisals of drugs between 2000 and 2004 did not reduce the number of prescription items dispensed and net ingredient costs in the ambulatory care of the NHS in England and Wales. CONCLUSIONS: Cost-effectiveness appraisals as performed by NICE or the German Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) are a useful and important tool to enhance the discussion about methods and acceptance of evidence-based medicine in general.

Ceftriaxone versus other cephalosporins for perioperative antibiotic prophylaxis: a meta-analysis of 43 randomized controlled trials.

The efficacy of ceftriaxone versus other cephalosporins in the perioperative prophylaxis of surgical wound, urinary tract and respiratory tract infections was compared in a meta-analysis of randomized controlled trials published between 1986 and 1996, identified from the Medline, Embase, SIGLE, ROPU, DHSS-Data and Medikat Cologne databases. Studies were grouped by type of infection, operative specialty, wound classification, study quality and other factors, and assessed for relative risk (RR). Forty-three studies with a total of 13,482 patients met our inclusion criteria. RR for surgical wound infection (n = 13,303 patients) was 30% lower in the ceftriaxone versus control groups [98.3% confidence interval (CI): 0.55-0.89; p = 0.0002]. In urinary tract infections (n = 8,865 patients), the primary analysis of all studies showed marked superiority for ceftriaxone (RR: 0.53; 98.3% CI: 0.43-0.67) but not in studies with CDC-defined infections (RR: 0.63; 98.3% CI: 0.36-1.12). In both types of infection, ceftriaxone was superior in contaminated operations. The data showed no advantage for ceftriaxone in other operations. In respiratory tract infections (n = 9,567 patients), there was no significant difference: the RR was 0.81 (98.3% CI: 0.61-1.09; p = 0.04).