Moving somatic gene editing to the clinic: routes to market access and reimbursement in Europe.

Somatic gene editing (SGE) holds great promise for making genetic therapy possible for many monogenic conditions very soon. Is our current system of European market authorization and reimbursement ready for the expected tsunami of gene therapies? At a recent workshop of the Netherlands ZonMw consortium on ethical, legal, and social implications of personalized medicine, we discussed the current possibilities for bringing new gene therapies to the clinic. In Europe, it is not yet clear whether the route via the European medicines agency as an advanced therapy medicinal product is the most appropriate for evaluation of highly personalized SGE applications, although this may optimally guarantee safety and effectiveness. Compassionate use may ensure faster access than the centralized procedure but does not stimulate the commercial development of products. Prescription to named patients may only provide adequate access for single patients. Temporary authorization of use may allow access to medication half a year before formal market authorization has been granted, but may also have large budget impacts. Magistral compounding under a hospital exemption may be an attractive solution for rare, tailor-made applications at an acceptable price. To approve local experimental use of a therapy on a case-by-case basis may be fast, but does not guarantee optimal safety, effectiveness, and broad implementation. We argue that alternative routes should be considered for products developed for a market of large groups of patients versus unique personalized treatments. A balance between scientific evidence for safety and effectiveness, affordability, and fast access may demand a range of alternative solutions.

Pharmacoepidemiology of testosterone: Impact of reimbursement policy on curbing off-label prescribing.

OBJECTIVES: To estimate the impact on testosterone prescribing over 3 years following the 2015 tightening of Pharmaceutical Benefits Scheme (PBS) criteria. DESIGN: Analysis of testosterone prescribing data from PBS and private (non-PBS) sources between 2012 and 2018 covering 2015 change in PBS prescribing criteria. MAIN OUTCOME MEASURES: New and total PBS testosterone prescriptions estimating usage by quarter analyzed by product type, patient age-group, indication and prescriber type. Total national testosterone prescriptions (private plus PBS) was verified from an independent data supplier (IQVIA). RESULTS: PBS usage peaked in 2014 declining by 30% in 2017-8 with PBS prescribing covering a fall from 97.6% by usage in 2014 to 74% in 2017-18 of all testosterone prescribing. The tighter 2015 PBS restrictions sustained the selective reduction in GP initiation of prescriptions for middle-aged men without pathological hypogonadism whereas specialist initiations and prescription for adult hypogonadism or pediatric/prepubertal indications were largely unaffected. CONCLUSIONS: The tightening of PBS criteria from 1 April 2015 to curb off-label prescribing remained effective and selective over 3 years yet total national testosterone prescribing continued with little change, reflecting a shift to private prescriptions. The continuation of off-label testosterone prescribing for unproven indications suggests that long-term androgen dependence is created in men without pathological hypogonadism who commence testosterone. This highlights the need to avoid prescribing testosterone to men without pathological hypogonadism in the absence of sound evidence of efficacy and safety, the latter including the little unrecognized risks of long-term androgen dependency when trying to quit.

Patient Length of Stay Under the Two-Midnight Rule: Assessing the Accuracy of Providers' Predictions.

EXECUTIVE SUMMARY: We sought to determine emergency medicine physicians' accuracy in designating patients' disposition status as "inpatient" or "observation" at the time of hospital admission in the context of Medicare's Two-Midnight rule and to identify characteristics that may improve the providers' predictions. We conducted a 90-day observational study of emergency department (ED) admissions involving adults aged 65 years and older and assessed the accuracy of physicians' disposition decisions. Logistic regression models were fit to explore associations and predictors of disposition. A total of 2,257 patients 65 and older were admitted through the ED. The overall error rate in physician designation of observation or inpatient was 36%. Diagnoses most strongly associated with stays lasting less than two midnights included diverticulitis, syncope, and nonspecific chest pain. Diagnoses most strongly associated with stays lasting two or more midnights included orthopedic fractures, biliary tract disease, and back pain. ED physicians inaccurately predicted patient length of stay in more than one third of all patients. Under the Two-Midnight rule, these inaccurate predictions place hospitals at risk of underpayment and patients at risk of significant financial liability. Further work is needed to increase providers' awareness of the financial repercussions of their admission designations and to identify interventions that can improve prediction accuracy.

Spillover effects of state medicaid antipsychotic prior authorization policies in US commercially insured youth.

PURPOSE: To evaluate spillover effects of Medicaid antipsychotic prior authorization (PA) policies among commercially insured youth. METHODS: Commercially insured youth residing in nine US states that implemented PA exclusively for antipsychotics in 2011 or 2012 were identified using a 10% random sample of enrollees in the IQVIA PharMetrics Plus database spanning 2007 to 2015. Youth were included if they were ≤18 years, met the age criteria of the PA at the time of dispensing, and had at least 1 month of prescription drug coverage from 2007 to 2015. The primary outcome of interest was the monthly prevalence of antipsychotics. We implemented segmented regression of interrupted time series analysis to estimate changes in the monthly prevalence of targeted medications, overall and stratified by age. Trends were compared in the 4-year period before and the 3-year period after implementation of PA policies. RESULTS: Antipsychotics prescribing significantly decreased 6.74/10 000 (95% CI, -9.04 to -4.44) enrollees per month immediately after PA implementation. However, PA was not associated with significant long-term trend changes (-0.06; 95% CI, -0.16 to 0.03). Antipsychotic prescribing in children <12 years-old significantly decreased 0.14/10 000 (95% CI, -0.21 to -0.07) enrollees per month after PA implementation, while prescribing in adolescents 12 to 18 years-old significantly increased 0.32/10 000 (95% CI, 0.16 to 0.47) enrollees per month. CONCLUSION: While Medicaid PA polices for antipsychotic oversight did not affect overall prescribing, there were spillover effects in U.S. commercially insured children <12 years-old. This suggests that state-level Medicaid policies intended to improve the quality of care and safe use of antipsychotics can have broad reach.

Impact of regulatory changes on pharmacist-delivered telehealth during the COVID-19 pandemic.

The 2020 coronavirus disease pandemic in the United States has created a dramatic need for the rapid implementation of telehealth services in areas of the country where telehealth is limited in scope. This implementation would not be possible without changes in how the Centers for Medicare and Medicaid Services provide reimbursement for these services. Reimbursement options remain open to pharmacists, but depend on local regulation or the ability to alter practice at the site. Though pharmacists provide high-quality direct patient care, they are excluded from seeking compensation for providing this care, even as the nation expands the telehealth model. This overview shows that despite changes in telehealth service compensation for health care providers, pharmacists remain unable to seek appropriate compensation for their direct patient care services.

Physician Reimbursement: Fee-for-Service, Accountable Care, and the Future of Bundled Payments.

In 1992, the use of relative value units to link a particular payments with specific services was initiated to replace traditional fee for service. The system incentivizes volume rather than quality. In 1997, initiatives were formalized to emphasize quality measures. Physicians must participate in the Merit-based Incentive Payment System (MIPS). Physicians can opt out of MIPS if they participate in an Alternative Payment Model such as Bundled Payments. Reimbursement based on an episode of care reduces perceived incentive to increase volumes, but may result in difficulty with access to care for patients with complex medical issues or significant comorbidities.

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.

Advocating for Washington state ARNP payment parity.

Workforce and reimbursement data were collected from a 2018 survey of Washington state advanced registered nurse practitioners (ARNPs). Survey results will be used to improve workforce planning and advocate for payment parity legislation requiring health plans to pay ARNPs the same as physicians for the same service.

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.