PARC report: a perspective on the state of clinical pharmacogenomics testing.

In this Perspective, the authors discuss the state of pharmacogenomics testing addressing a number of advances, challenges and barriers, including legal ramifications, changes to the regulatory landscape, coverage of testing and the implications of direct-to-consumer genetic testing on the provision of care to patients. Patient attitudes toward pharmacogenomics testing and associated costs will play an increasingly important role in test acquisition and subsequent utilization in a clinical setting. Additional key steps needed include: further research trials demonstrating clinical utility and cost-effectiveness of pharmacogenetic testing, evidence review to better integrate genomic information into clinical practice guidelines in target therapeutic areas to help providers identify patients that may benefit from pharmacogenetic testing and engagement with payers to create a path to reimbursement for pharmacogenetic tests that currently have sufficient evidence of clinical utility. Increased adoption of testing by payers and improved reimbursement practices will be needed to overcome barriers, especially as the healthcare landscape continues to shift toward a system of value-based care.

Efficacy and Effectiveness Too Trials: Clinical Trial Designs to Generate Evidence on Efficacy and on Effectiveness in Wide Practice.

Efficacy trials, designed to gain regulatory marketing approval, evaluate drugs in optimally selected patients under advantageous conditions for relatively short time periods. Effectiveness trials, designed to evaluate use in usual practice, assess treatments among more typical patients in real-world conditions with longer follow-up periods. In "efficacy-to-effectiveness (E2E) trials," if the initial efficacy trial component is positive, the trial seamlessly transitions to an effectiveness trial component to efficiently yield both types of evidence. Yet more time could be saved by simultaneously addressing efficacy and effectiveness in an "efficacy and effectiveness too (EE2) trial." Additionally, hybrids of the E2E and EE2 approaches with differing degrees of overlap of the two components could allow flexibility for specific drug development needs. In planning EE2 trials, each stakeholder's current and future needs, incentives, and perspective must be considered. Although challenging, the ultimate benefits to stakeholders, the health system, and the public should justify this effort.

Association Between Medicare's Mandatory Hospital Value-Based Purchasing Program and Cost Inefficiency.

BACKGROUND: The Patient Protection and Affordable Care Act instituted pay-for-performance programs, including Hospital Value-Based Purchasing (HVBP), designed to encourage hospital quality and efficiency. OBJECTIVE AND METHOD: While these programs have been evaluated with respect to their implications for care quality and financial viability, this is the first study to assess the relationship between hospitals' cost inefficiency and their participation in the programs. We estimate a translog specification of a stochastic cost frontier with controls for participation in the HVBP program and clinical and outcome quality for California hospitals for 2012-2015. RESULTS: The program-participation indicators' parameters imply that participants were more cost inefficient than their peers. Further, the estimated coefficients for summary process of care quality indexes for three health conditions (acute myocardial infarction, pneumonia, and heart failure) suggest that higher quality scores are associated with increased operating costs. CONCLUSION: The estimated coefficients for the outcome quality variables suggest that future determination of HVBP payment adjustments, which will depend solely on mortality rates as measures of clinical care quality, may not only be aligned with increasing healthcare quality but also reducing healthcare costs.

[Biosimilars and the efficiency principle]. / Biosimilars und das Wirtschaftlichkeitsgebot.

Biosimilars are subject to the efficiency evaluation according to section 106 Social Code Book Five (SGB V). The specific evaluation method influences the physician's prescription behaviour. In the case of an individual prescription limit evaluation (Richtgrößenprüfung), the prescription of biosimilars would usually not result in recourse but, as a start, in the initiation of the evaluation proceedings. Starting from 2017, the individual prescription limit evaluation will be cancelled. The active ingredient evaluation (Wirkstoffprüfung) expected instead at a regional level may provide for biosimilar to original drug ratios and result in recourses if these ratios are missed. First agreements on specific evaluation proceedings at a regional level are expected for this year.

[Termination of Reimbursement of Arthroscopy in Osteoarthritis of the Knee: Is This Decision Based on Scientific Grounds?] / Ausschluss der Arthroskopie bei Gonarthrose aus dem GKV-Leistungskatolog: Beruht diese Entscheidung auf wissenschaftlichen Kriterien?

Background In Germany, arthroscopy of the knee used to be an accepted procedure in the treatment of osteoarthritis of the knee. However, as of April 1, 2016 reimbursement for this procedure has been discontinued. This was a decision of the Joint Federal Committee (Gemeinsamer Bundesausschuss, G-BA). That decision was based on a report of the German Institute for Quality and Efficiency in Health Care (IQWiG). This report is essentially based on a few studies, three of which have been published in the renowned New England Journal of Medicine. According to the IQWiG, there is "no hint, indication or proof of a benefit of therapeutic arthroscopy" in osteoarthritis of the knee. Since this statement does not coincide with clinical observations commonly made by orthopaedic surgeons, the aim of this analysis was to evaluate the aforementioned studies according to criteria of evidence-based medicine. Material and Methods The three studies on which the IQWiG report is essentially based (Moseley et al. 2002, Kirkley et al. 2008 and Katz et al. 2013), all published in the New England Journal of Medicine, were analyzed according to the standards of evidence-based medicine. Results Although all of the evaluated studies were randomized controlled studies, there were considerable and serious deficiencies. These deficiencies include, among others, sampling bias that affects external validity and selection bias that affects internal validity. While a sham operation was performed in one study, resulting in an ideal blinding of study participants, that study used a non-validated primary outcome measure. That outcome score has not been used in subsequent publications and the algorithm presented for the calculation of the outcome score was incorrect. Although the other studies used validated main outcome measures, patients in those studies were not blinded. A number of further deficiencies were identified as well. Conclusion The studies on which the decision of the Joint Federal Committee is based do have several significant and at times severe methodological deficiencies. For instance, the results of these studies cannot be generalized to all patients suffering from osteoarthritis of the knee, solely on the basis of patient selection. Many of these deficiencies have not been mentioned till now, neither in the literature nor in the final report authored by the IQWiG. Therefore, it seems unlikely that the Joint Federal Committee was aware of these deficiencies when it decided to discontinue reimbursement for arthroscopy in patients with osteoarthritis of the knee. Unfortunately, not all patients suffering from osteoarthritis of the knee respond to conservative therapy. By discontinuing reimbursement for arthroscopy in this patient group, a commonly used treatment option has been withdrawn. The proportion of such patients was 30% after 6 months and 35% after 12 months in one of the studies considered by the IQWiG. It is hence conceivable that the indication for joint replacement surgery could become more generous after the withdrawal of arthroscopy as an alternative treatment option. In summary, it became clear that, given the variety and severity of the deficiencies of the underlying studies, the decision of the Joint Federal Committee could not have been based on scientific criteria. To this extent, it seems appropriate to revive the discussion about the exclusion of arthroscopy from the performance catalogue of the German Health Insurance System.

The Use of Economic Evaluation to Inform Newborn Screening Policy Decisions: The Washington State Experience.

POLICY POINTS: Newborn screening not only saves lives but can also yield net societal economic benefit, in addition to benefits such as improved quality of life to affected individuals and families. Calculations of net economic benefit from newborn screening include the monetary equivalent of avoided deaths and reductions in costs of care for complications associated with late-diagnosed individuals minus the additional costs of screening, diagnosis, and treatment associated with prompt diagnosis. Since 2001 the Washington State Department of Health has successfully implemented an approach to conducting evidence-based economic evaluations of disorders proposed for addition to the state-mandated newborn screening panel. CONTEXT: Economic evaluations can inform policy decisions on the expansion of newborn screening panels. This article documents the use of cost-benefit models in Washington State as part of the rule-making process that resulted in the implementation of screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and 4 other metabolic disorders in 2004, cystic fibrosis (CF) in 2006, 15 other metabolic disorders in 2008, and severe combined immune deficiency (SCID) in 2014. METHODS: We reviewed Washington State Department of Health internal reports and spreadsheet models of expected net societal benefit of adding disorders to the state newborn screening panel. We summarize the assumptions and findings for 2 models (MCAD and CF) and discuss them in relation to findings in the peer-reviewed literature. FINDINGS: The MCAD model projected a benefit-cost ratio of 3.4 to 1 based on assumptions of a 20.0 percentage point reduction in infant mortality and a 13.9 percentage point reduction in serious developmental disability. The CF model projected a benefit-cost ratio of 4.0-5.4 to 1 for a discount rate of 3%-4% and a plausible range of 1-2 percentage point reductions in deaths up to age 10 years. CONCLUSIONS: The Washington State cost-benefit models of newborn screening were broadly consistent with peer-reviewed literature, and their findings of net benefit appear to be robust to uncertainty in parameters. Public health newborn screening programs can develop their own capacity to project expected costs and benefits of expansion of newborn screening panels, although it would be most efficient if this capacity were shared among programs.

A Cost-Effectiveness Tool for Informing Policies on Zika Virus Control.

BACKGROUND: As Zika virus continues to spread, decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert. For example, to combat the current Zika outbreak the US President requested the allocation of $1.8 billion from Congress in February 2016. METHODOLOGY/PRINCIPAL FINDINGS: Illustrated through an interactive tool, we evaluated how the number of Zika cases averted, the period during pregnancy in which Zika infection poses a risk of microcephaly, and probabilities of microcephaly and Guillain-Barré Syndrome (GBS) impact the cost at which an intervention is cost-effective. From Northeast Brazilian microcephaly incidence data, we estimated the probability of microcephaly in infants born to Zika-infected women (0.49% to 2.10%). We also estimated the probability of GBS arising from Zika infections in Brazil (0.02% to 0.06%) and Colombia (0.08%). We calculated that each microcephaly and GBS case incurs the loss of 29.95 DALYs and 1.25 DALYs per case, as well as direct medical costs for Latin America and the Caribbean of $91,102 and $28,818, respectively. We demonstrated the utility of our cost-effectiveness tool with examples evaluating funding commitments by Costa Rica and Brazil, the US presidential proposal, and the novel approach of genetically modified mosquitoes. Our analyses indicate that the commitments and the proposal are likely to be cost-effective, whereas the cost-effectiveness of genetically modified mosquitoes depends on the country of implementation. CONCLUSIONS/SIGNIFICANCE: Current estimates from our tool suggest that the health burden from microcephaly and GBS warrants substantial expenditures focused on Zika virus control. Our results justify the funding committed in Costa Rica and Brazil and many aspects of the budget outlined in the US president's proposal. As data continue to be collected, new parameter estimates can be customized in real-time within our user-friendly tool to provide updated estimates on cost-effectiveness of interventions and inform policy decisions in country-specific settings.

[Requirements for drug approval and additional benefits assessment: Regulatory aspects and experiences]. / Anforderungen an Zulassung und Zusatznutzenbewertung von Arzneimitteln : Regulatorische Aspekte und Erfahrungen.

The early assessment of benefits of newly approved drugs with novel active substances or new applications, which came into force on 1 January 2011 still represents a challenge to all parties involved. This article highlights the definitions, regulatory requirements and interaction between drug marketing approval and early assessment of benefits in Germany. The constellation of an extensively harmonized European and even international drug authorization process with a predominantly national regulation of drug reimbursement situation inevitably causes friction, which could be markedly reduced through early joint advisory discussions during the planning phase for pivotal clinical trials. During the year 2015 the Federal Institute for Drugs and Medical Devices (BfArM) carried out 300 scientific advice procedures of which 34 were concerned with applications in the field of indications for the central nervous system (CNS). In comparison 98 advisory meetings were held by the Federal Joint Committee (G-BA) of which the BfArM provided advice in 12 instances and in 2 cases on CNS indications. Study design, endpoints and appropriate comparative therapies are the key issues in exchanges and discussions between the BfArM, the G­BA and applicants. Under these aspects the BfArM and G­BA promote an early and consistent involvement in early advice procedures regarding the prerequisites for drug approval and assessment of additional benefits.

Internal Controlling of a Radiology Department.

Caused by legal reform initiatives there is a continuous need to increase effectiveness and efficiency in hospitals and surgeries, and thus to improve processes.Consequently the successful management of radiological departments and surgeries requires suitable structures and optimization processes to make optimization in the fields of medical quality, service quality and efficiency possible.In future in the DRG System it is necessary that the organisation of processes must focus on the whole clinical treatment of the patients (Clinical Pathways). Therefore the functions of controlling must be more established and adjusted. On the basis of select Controlling instruments like budgeting, performance indicators, process optimization, staff controlling and benchmarking the target-based and efficient control of radiological surgeries and departments is shown.