The cost-effectiveness of bevacizumab, ranibizumab and aflibercept for the treatment of age-related macular degeneration-A cost-effectiveness analysis from a societal perspective.

BACKGROUND: The discussion on the use of bevacizumab is still ongoing and often doctors are deterred from using bevacizumab due to legal or political issues. Bevacizumab is an effective, safe and inexpensive treatment option for neovascular age-related macular degeneration (AMD), albeit unregistered for the disease. Therefore, in some countries ophthalmologists use the equally effective but expensive drugs ranibizumab and aflibercept. We describe the economic consequences of this dilemma surrounding AMD treatment from a societal perspective. METHODS: We modelled cost-effectiveness of treatment with ranibizumab (as-needed), aflibercept (bimonthly) and bevacizumab (as-needed). Effectiveness was estimated by systematic review and meta-analysis. The drug with the most favourable cost-effectiveness profile compared to bevacizumab was used for threshold analyses. First, we determined how much we overspend per injection. Second, we calculated the required effectiveness to justify the current price and the reasonable price for a drug leading to optimal vision. Finally, we estimated how much Europe overspends if bevacizumab is not first choice. RESULTS: Bevacizumab treatment costs €27,087 per year, about €4,000 less than aflibercept and €6,000 less than ranibizumab. With similar effectiveness for all drugs as shown by meta-analysis, bevacizumab was the most cost-effective. Aflibercept was chosen for threshold analyses. Aflibercept costs €943 per injection, but we determined that the maximum price to be cost-effective is €533. Alternatively, at its current price, aflibercept should yield about twice the visual gain. Even when optimal vision can be achieved, the maximum price for any treatment is €37,453 per year. Most importantly, Europe overspends €335 million yearly on AMD treatment when choosing aflibercept over bevacizumab. CONCLUSION: Bevacizumab is the most cost-effective treatment for AMD, yet is not the standard of care across Europe. The registered drugs ranibizumab and aflibercept lead to large overspending without additional health benefits. Health authorities should consider taking steps to implement bevacizumab into clinical practice as first choice.

New Therapeutic Uses for Existing Drugs.

Eighty percent of drugs that enter human clinical testing are never approved for use. This means that for every five drugs that make it into the clinic, there are four that failed to show effectiveness for treating the disease or condition the drug was designed to treat.This high failure rate means there are many existing, partially developed therapeutic candidates with known pharmacology, formulation, and potential toxicity. Finding new uses for existing experimental drugs or biologics "repositioning" builds upon previous research and development efforts, so new candidate therapies can be advanced to clinical trials for a new use more quickly than starting from scratch.Federal funding initiatives in the U.S. and UK started to support pre-clinical /or early stage trials for repositioning existing experimental drugs or biologics (therapies). This chapter covers some of the process issues that have been solved and the remaining challenges that are still in need of solutions. The chapter is primarily written from a U.S. federal funding perspective. The general concepts could be applied more globally to benefit rare and neglected disease populations. The drug development and process bottlenecks are the same for both rare and common disease.

[Iron substitution in outpatients in Switzerland: Increase of costs associated with intravenous administration]. / Ambulante Eisensubstitution in der Schweiz - Kostensteigerung infolge venöser Applikation.

Iron anaemia and iron-deficient erythropoiesis are treated with oral iron supplements. For chronic haemodialysis or in the case of therapy failure or intolerance to oral iron therapy, intravenous supplements are administered. The costs of iron supplements borne by statutory health care insurance had strongly increased during the observation period from 2006 to 2010. Based on the invoice data of a large health insurance company with a market share of around 18 %, prescription data of iron preparations and laboratory tests were analysed and extrapolated to the Swiss population. During the 5-year observation period, costs of intravenous iron substitution increased by 16.5 m EUR (340.3 %) and the number of individuals treated by 243.5 %. A sharp rise was observed in women of menstruating age, which was mainly due to prescriptions issued by primary care physicians. More than 8 % of intravenous iron substitutions were administered without prior laboratory analysis,and must therefore be regarded as off-label use. A cost-benefit analysis is needed to demonstrate the additional value of intravenous over oral iron supplementation, and intravenous iron supplementation should be administered only to patients with proven iron deficiency.

Prevalence of off-label use and spending in 2010 among patent-protected chemotherapies in a population-based cohort of medical oncologists.

PURPOSE: The prevalence of off-label anticancer drug use is not well characterized. The extent of off-label use is a policy concern because the clinical benefits of such use to patients may not outweigh costs or adverse health outcomes. METHODS: Prescribing data from IntrinsiQ Intellidose data systems, a pharmacy software provider maintaining a population-based cohort database of medical oncologists, was analyzed. Use of the most commonly prescribed anticancer drugs ("chemotherapies") that were patent protected and administered intravenously to patients in 2010 was examined. Use was classified as "on-label" if the cancer site, stage, and therapy line met the US Food and Drug Administration (FDA)-approved indication. All other use was "off-label." Off-label use was divided by whether it conformed to National Comprehensive Care Network (NCCN) Compendium recommendations, a basis of insurer coverage policies. IMS Health National Sales Perspectives was used to estimate national spending by use category. RESULTS: Ten chemotherapies met inclusion criteria. On-label use amounted to 70%, and off-label use amounted to 30%. Fourteen percent of use conformed to an NCCN-supported off-label indication, and 10% of off-label use was associated with an FDA-approved cancer site, but an NCCN-unsupported cancer stage and/or line of therapy. Total national spending on these chemotherapies amounted to $12 billion (B; $7.3B on-label, $2B off-label and NCCN supported; $2.5B off-label and NCCN unsupported). CONCLUSION: Commonly used, novel chemotherapies are more often used on-label than off-label in contemporary practice. Off-label use is composed of a roughly equal mix of chemotherapy applied in clinical settings supported by the NCCN and those that are not.

Unsupported off-label chemotherapy in metastatic colon cancer.

BACKGROUND: Newer systemic therapies have the potential to decrease morbidity and mortality from metastatic colorectal cancer, yet such therapies are costly and have side effects. Little is known about their non-evidence-based use. METHODS: We conducted a retrospective cohort study using commercial insurance claims from UnitedHealthcare, and identified incident cases of metastatic colon cancer (mCC) from July 2007 through April 2010. We evaluated the use of three regimens with recommendations against their use in the National Comprehensive Cancer Center Network Guidelines, a commonly used standard of care: 1) bevacizumab beyond progression; 2) single agent capecitabine as a salvage therapy after failure on a fluoropyridimidine-containing regimen; 3) panitumumab or cetuximab after progression on a prior epidermal growth factor receptor antibody. We performed sensitivity analyses of key assumptions regarding cohort selection. Costs from a payer perspective were estimated using the average sales price for the entire duration and based on the number of claims. RESULTS: A total of 7642 patients with incident colon cancer were identified, of which 1041 (14%) had mCC. Of those, 139 (13%) potentially received at least one of the three unsupported off-label (UOL) therapies; capecitabine was administered to 121 patients and 49 (40%) likely received it outside of clinical guidelines, at an estimated cost of $718,000 for 218 claims. Thirty-eight patients received panitumumab and six patients (16%) received it after being on cetuximab at least two months, at an estimated cost of $69,500 for 19 claims. Bevacizumab was administered to 884 patients. Of those, 90 (10%) patients received it outside of clinical guidelines, at an estimated costs of $1.34 million for 636 claims. CONCLUSIONS: In a large privately insured mCC cohort, a substantial number of patients potentially received UOL treatment. The economic costs and treatment toxicities of these therapies warrant increased efforts to stem their use in settings lacking sufficient scientific evidence.

[Public financing for off-label use of drugs].

Off-label use of drugs is common in all areas of medicine, but is specifically prevalent in pediatrics, oncology and in treating rare diseases. Such use may benefit patients, but on the other hand, there is concern about the safety aspects of these treatments. Besides the legal, ethical and safety issues associated with off-label use, arises the issue of whether such prescribing should be reimbursed by public funds. According to Ministry of Health (MoH) guidelines, the committee in charge of updating the National List of Health Services (NLHS) did not discuss, from its inception and until its deliberations at the end of 2008, off-label indications. This policy was to protect the Israeli pharmaceutical registration mechanism, prevent registration bypass mechanisms and not grant use of public funds for reimbursing treatments for which there were insufficient evidence on safety and efficacy. The patients most affected by this policy were the ones that could not benefit from a drug that was not in the NLHS for their medical condition and had to pay for it out of pocket. Occasionally, health plans agreed to subsidize critically needed off-label treatments, although they did not receive public funding for off-label indications. In this article we review the problems associated with off-label prescribing, the reasons why the MoH changed its policy at the beginning of 2009 to permit, in very special circumstances, reimbursement of off-label treatment. We also provide a brief summary of off-label policies in a few western countries.

[Off-label use of acetazolamide in a patient with familial hemiplegic migraine and concomitant psychotic episodes]. / Off-label-Behandlung eines Patienten mit rezidivierender familiärer hemiplegischer Migräne und begleitenden vorübergehenden psychotischen Episoden.

A 42-year-old patient with cognitive deficits due to childhood meningitis suffered from recurrent episodes of familial hemiplegic migraine. Additionally, he developed concomitant psychotic episodes requiring subsequent in-patient psychiatric treatment. Following combined neurological and psychiatric treatment he always recovered from the episodes within a few weeks time. Prophylactic treatment of migraine using topiramate and acetazolamide (off-label) prevented attacks for several months. When off-label compensation was refused and, as a consequence, the drug discontinued, hemiplegia relapsed within a few days. Hence, acetazolamide was prescribed again and the family paid for the medication. Since that time, the patient did not show severe attacks for at least 8 months apart from a transient attack induced by acute flu-like illness.