Publicly accessible evidence of health-related quality of life benefits associated with cancer drugs approved by the European Medicines Agency between 2009 and 2015.

OBJECTIVE: Health-related quality of life (HRQoL) is one of the most important patient-relevant study end-points for the direct measurement of the benefit of cancer drugs. Therefore, our aim is to detect cancer indications with no published information on HRQoL at the time of European Medicines Agency (EMA) approval and monitor any reported HRQoL evidence updates after at least three years of follow-up. METHODS: We included all cancer indications that were approved by the EMA between January 2009 and October 2015. Our main sources of information were the EMA website, clinicaltrials.gov and a systematic literature search in PubMed. Information on HRQoL outcomes was extracted alongside evidence on median overall survival. RESULTS: In total, we identified 110 indications, of which more than half (n = 58, 53%) were lacking available information on HRQoL assessments at the time of EMA approval. After a monitoring period of at least three years, 24 updates were identified, resulting in 34 (31%) therapies where information on HRQoL was still not available. For the 76 therapies with reported information on HRQoL, cancer-specific instruments were mostly used (n = 49/76). Regarding cumulative evidence on median overall survival and HRQoL, 33 (n = 33/110, 30%) as well as 15 (n = 15/110, 14%) cancer drugs were lacking information on both study end-points at the time of approval and after monitoring, respectively. CONCLUSION: Our results demonstrate that there is an urgent need of routine re-evaluation of reimbursed cancer drugs with initially missing information on major outcomes. Standardisation of the typology and quality of HRQoL assessments need to be improved to allow better comparability of results.

Contributions to the Neurosurgery Political Action Committee (NeurosurgeryPAC): A Historical Perspective.

BACKGROUND: The political action committee (PAC) of the American Association of Neurological Surgeons, known as NeurosurgeryPAC, was formed in August 2005 to strengthen neurosurgical advocacy efforts. Since its establishment, NeurosurgeryPAC has made nonpartisan, direct campaign contributions to hundreds of candidates for the U.S. Senate and U.S. House of Representatives. METHODS: Historical contribution data for 2005-2018 was obtained from NeurosurgeryPAC. Data analyzed by year, and a 2-year election cycle included total amount raised, number of contributors, average donation, and percent participation. NeurosurgeryPAC contribution amounts for election cycles were also compared with those of other physician PACs. RESULTS: NeurosurgeryPAC has raised $2,953,870 since its inception in 2005, for an average of $210,991 per year. For this fundraising, the average annual donation amount is $796 per donor. The number of unique contributors per cycle has varied from 316-504, with an average of 389 individuals per annum and a participation rate of 7.8%. To date, the total amount raised in election years ($1,605,940) is 16.1% higher than that raised in nonelection years ($1,347,930). Among 28 physician PACs, NeurosurgeryPAC has ranked as high as 13 and as low as 17 in total hard money contributions. The orthopedic, neurology and general surgery PACs have consistently ranked higher than NeurosurgeryPAC, whereas the otolaryngology, spine, and plastic surgery PACs have ranked lower. CONCLUSIONS: Since its creation, NeurosurgeryPAC has collected a steady stream of donations to support political candidates. These donations have helped lawmakers who are supportive of policy issues important to neurosurgery, particularly physician reimbursement, medical liability reform, and graduate medical education. However, there remains a significant opportunity to increase the neurosurgeon participation rate in this vital organization. It is truly through advocacy that we will be able to positively affect the future of neurologic surgery in the United States.

Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project.

Background: Off-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based healthcare, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here, we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence. Methods/ design: We will extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We will systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer. Discussion: Our study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse western healthcare system.

Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed. OBJECTIVE: The aim was to investigate the comparative effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens and compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC, through an updated systematic review and meta-analysis of concurrent or non-concurrent observational cohort studies, to guide authorities and the judiciary. METHOD: A systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures included OS, PFS, post-progression survival (PPS), Response Evaluation Criteria In Solid Tumors (RECIST), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated. RESULTS: A total of 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities and concerns with the heterogeneity of the studies. CONCLUSION: The results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation, that need to be considered.

[Innovative medicinal products: the new criteria of the Italian Medicines Agency.] / Farmaci innovativi: i nuovi criteri dell'Agenzia Italiana del Farmaco.

The Italian Medicines Agency (AIFA), which has the dual function of a regulatory and a reimbursement authority, has recently established new criteria to define innovative medicinal products. Indeed, the decision making process to grant the innovative status is based on the evaluation of the unmet medical need, the added therapeutic value compared to existing therapeutic options and the overall quality of clinical evidence, which is assessed based on the GRADE system. Following this evaluation, if a medicinal product is granted the status of "full innovativeness" for a specific therapeutic indication, its manufacturer can access dedicated yearly funds amounting to 500 million Euros each, depending on the type of medicine (one fund for oncology, the other for all other innovative medicinal products). Alternatively, the product can be granted the status of "conditional innovativeness" which allows immediate access to all Regional formularies, with no additional re-assessments at the local level. The third possible outcome is that no innovativeness is recognized. Starting from January 2018, a full report explaining the rationale for the Agency Committee's decision is made publicly available on the AIFA's website.

Chance of reimbursement for ADD-ON therapies in Poland and in the world - review of the reimbursement recommendations

INTRODUCTION: Oncology drugs combined with standard therapies (so-called add-on therapies, e.g. bevacizumab, palbociclib) often receive negative recommendations regarding the legitimacy of public financing, issued by government agencies responsible for their assessment, i.e. health technology assessment agencies. The aim of the study was to estimate the scale of the problem related to the reimbursement of add-on therapies used in the treatment of breast and genitourinary cancers in Poland and in the world. MATERIAL AND METHODS: A multimodal approach was used to select add-on therapies. The reimbursement routes were analysed in 8 reference countries (Poland, Canada, England, Wales, France, Scotland, Australia, New Zealand). Based on a systematic search, data for breast and urogenital cancers were included. RESULTS: A total of 68 reimbursement documents for add-on therapies were identified. The analysis showed that in Poland, 20% of innovative schemes including add-on therapies should be reimbursed, while in the world the percentage of positive recommendations reaches 56%. It was observed that globally (including data for Poland) the chance for a favorable reimbursement recommendation for add-on therapies is 53%, with 29% being positive recommendations with limitations. In Poland, the majority of negative recommendations concern genitourinary cancers in comparison to breast cancer (83% vs 75%). CONCLUSIONS: Poland is at the head of the countries in terms of the number of negative reimbursement recommendations. Bearing in mind the world's need of modifying the criteria for the evaluation of oncological therapies in the context of the possibility of their reimbursement, one should expect a change in the approach to the assessment of the legitimacy of financing innovative add-on therapies in Poland.

Maximize Reimbursement and Minimize Risk Under the Medicare Access and Children's Health Insurance Program Reauthorization Act (MACRA) and the Quality Payment Program (QPP).

The Congress recently passed legislation to repeal the Sustainable Growth Rate Formula and replace it with the Medicare Access and Children Health Plan Reauthorization Act's Quality Payment Program. The Quality Payment Program is designed to move physician payment from a volume-based to a value-based methodology. There are two pathways of payment that diverge and are differentiated by managing risks or managing rewards. The Merit-based Incentive Payment System (MIPS) is a competitive payment system that is budget neutral and results in defined winners and losers with potential losses/gains in payments from 4% in 2019 to 9% in 2022. Characteristically, this is not dissimilar to the Sustainable Growth Rate Formula of days past but with quality measures applied. The second pathway is that toward Alternative Payment Models (APMs) that allow clinicians to participate in payment models that that provide rewards for higher-quality, lower-cost care with entry bonuses as high as 5%. The Virginia Cardiac Services Quality Initiative, a well-known regional quality collaborative, was awarded a federal grant as a Support and Alignment Network 2.0 in September 2016. As an awardee, the Virginia Cardiac Services Quality Initiative is offering, free of charge, educational support to clinicians to understand the Medicare Access and Children Health Plan Reauthorization Act, MIPS, and APMs. These support services will include on-site education, continual evaluation, and guided transformation of practices to move from MIPS, a very competitive and possibly very difficult system for Society of Thoracic Surgeons members, toward Advanced APMs, where they can self-direct their measurement and rewards, allowing success financially under the Medicare Access and Children Health Plan Reauthorization Act.