Analysis of the Gene Therapies Authorized by the United States Food and Drug Administration and the European Medicines Agency.

BACKGROUND: Gene therapy, altering the genes inside human cells, has recently emerged as an alternative for preventing and treating disease. Concerns have been expressed about the clinical value and the high cost of gene therapies. OBJECTIVE: This study assessed the characteristics of the clinical trials, authorizations, and prices of gene therapies in the United States and the European Union. RESEARCH DESIGN: We collected regulatory information from the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and manufacturer-listed prices from the United States, UK, and Germany. Descriptive statistics and t tests were conducted in the study. RESULTS: As of January 1, 2022, the FDA and EMA authorized 8 and 10 gene therapies, respectively. The FDA and EMA granted orphan designation to all gene therapies except talimogene laherparepvec. Pivotal clinical trials were nonrandomized, open level, uncontrolled, phase I-III, and included a limited number of patients. Study primary outcomes were mainly surrogate endpoints without demonstration of direct patient benefit. The price of gene therapies at market entry ranged from $200,064 to $2,125,000 million. CONCLUSIONS: Gene therapy is used to treat incurable diseases that affect only a small number of patients (orphan diseases). Based on this, they are approved by the EMA and FDA with insufficient clinical evidence to ensure safety and efficacy, in addition to the high cost.

The American Public Health Association Endorses Single-Payer Health System Reform.

Health care is a human right. Achieving universal health insurance coverage for all US residents requires significant system-wide reform. The most equitable and cost-effective health care system is a public, single-payer (SP) system. The rapid growth in national health expenditures can be addressed through a system that yields net savings over projected trends by eliminating profit and waste. With universal health insurance coverage through SP financing, providers can focus on optimizing delivery of services, rather than working within a system covered by payers who have incentives to limit costs regardless of benefit. Rather, with a SP, the people act as their own insurer through a partnership with provider organizations where tax dollars work for everyone. Consumer choice is then based on the best care to meet need with no out-of-pocket payments. SP financing is the best option to ensure equity, fairness, and public health priorities align with medical needs, providing incentives for wellness. Consumer choice will drive market forces, not provider network profits or insurer restrictions. This approach benefits public health, as everyone will have universal access to needed care, with treatment plans developed by providers based on what works best for the patient. In 2021, the American Public Health Association adopted a policy statement calling for comprehensive reforms to implement a SP system. The proposed action steps in this policy will help build a healthier nation, saving lives and reducing wasted health care expenditures while addressing inequities rooted in social, demographic, mental health, economic, and political determinants.

Opioid prescribing practices at hospital discharge for surgical patients before and after the Centers for Disease Control and Prevention's 2016 opioid prescribing guideline.

BACKGROUND: The Centers for Disease Control and Prevention's (CDC) March 2016 opioid prescribing guideline did not include prescribing recommendations for surgical pain. Although opioid over-prescription for surgical patients has been well-documented, the potential effects of the CDC guideline on providers' opioid prescribing practices for surgical patients in the United States remains unclear. METHODS: We conducted an interrupted time series analysis (ITSA) of 37,009 opioid-naïve adult patients undergoing inpatient surgery from 2013-2019 at an academic medical center. We assessed quarterly changes in the discharge opioid prescription days' supply, daily and total doses in oral morphine milligram equivalents (OME), and the proportion of patients requiring opioid refills within 30 days of discharge. RESULTS: The discharge opioid prescription declined by -0.021 (95% CI, -0.045 to 0.003) days per quarter pre-guideline versus -0.201 (95% CI, -0.223 to -0.179) days per quarter post-guideline (p < 0.0001). Likewise, the mean daily and total doses of the discharge opioid prescription declined by -0.387 (95% CI, -0.661 to -0.112) and -7.124 (95% CI, -9.287 to -4.962) OME per quarter pre-guideline versus -2.307 (95% CI, -2.560 to -2.055) and -20.68 (95% CI, -22.66 to -18.69) OME per quarter post-guideline, respectively (p < 0.0001). Opioid refill prescription rates remained unchanged from baseline. CONCLUSIONS: The release of the CDC opioid guideline was associated with a significant reduction in discharge opioid prescriptions without a concomitant increase in the proportion of surgical patients requiring refills within 30 days. The mean prescription for opioid-naïve surgical patients decreased to less than 3 days' supply and less than 50 OME per day by 2019.

Substance use treatment services utilization and outcomes among probationers in drug courts compared to a matched cohort of probationers in traditional courts.

BACKGROUND AND OBJECTIVES: Drug courts provide an array of substance use treatments and community-based services for probationers struggling with substance use disorders. We assessed substance use treatment services utilization and related expenditures and relapse and recidivism outcomes and identified predictors of cost of provision of substance use treatment services in a matched cohort of Massachusetts probationers in drug courts and traditional courts. METHODS: This was an observational quasi-experimental study with 542 propensity-score-matched probationers initiating drug court between August 1, 2015 and February 28, 2018 and a minimum 6-month follow-up period. RESULTS: A significantly greater proportion of probationers in drug courts were female, self-reported opioids as their primary drug of choice, had a history of substance use treatment, and a high and very high risk of recidivism than their counterparts in traditional courts. We estimated that the provision of substance use treatment services was $1498 more expensive for probationers in drug courts than traditional courts (p = .054). There were no statistically significant differences in relapse or recidivism rates between court systems. DISCUSSION AND CONCLUSIONS: Probationer's age, gender, risk of recidivism at court intake, and enrollment length were strong predictors of expenditures on substance use treatment services. SCIENTIFIC SIGNIFICANCE: This was the first study to assess substance use treatment services utilization and outcomes among probationers in drug courts and traditional courts. Drug courts served the needs of probationers disproportionally impacted by nonserious drug-related offenses struggling with substance use disorders who were at a high and very high risk of recidivism at court intake.

Perioperative Prescribing Practices of Extended-Release Opioids in Noncancer Surgical Patients, 2015-2018.

BACKGROUND: Extended-release (ER) opioids are indicated for the management of persistent moderate to severe pain in patients requiring around-the-clock opioid analgesics for an extended period of time. Concerns have been raised regarding safety of ER opioids due to its potential for abuse and dependence. However, little is known about perioperative prescribing practices of ER opioids. This study assessed perioperative prescribing practices of ER opioids in noncancer surgical patients stratified by type of opioid exposure prior to admission and examined predictors of postoperative opioid administration in oral morphine equivalents (OME). METHODS: This was a retrospective cohort study using the University of California San Francisco Medical Center electronic health record data. This study included 25,396 adult noncancer patients undergoing elective surgery under general anesthesia in the period 2015-2018. The primary study outcome was predictors of postoperative administration of opioids in hospitalized surgical patients. Secondary outcomes included patients discontinued and initiated on ER opioids during their hospital stay. RESULTS: substance use disorder diagnosis and use of opioids, surgery type, and postoperative administration of nonopioid analgesics were associated with postoperative administration of opioids (P < .0001). The estimated adjusted mean (95% confidence interval [CI]) of postoperative administration of OME prior to admission in ER opioid users (170.08 mg; 147.08-196.67) was twice the amount for opioid-naïve patients (81.36 mg; 70.7-93.63; P < .0001). One in 5 prior to admission ER opioid users were weaned off ER opioids while hospitalized without adversely affecting their postoperative pain or hospital length of stay (LOS). Four of 5 patients who used ER opioids prior to admission also received ER opioids after surgery, whereas, 1 in 100 opioid-naïve patients received ER opioids during their hospital stay. CONCLUSIONS: We found significant variability in the perioperative prescribing practices of ER opioids in hospitalized noncancer surgical patients by use of opioids prior to admission and surgery type. Pain medicine practitioners and surgeons may play a significant role tackling the surgery-related risk of exposure to ER opioids and decreasing opioid-related complications.

Gender differences in mental health and substance use disorders and related healthcare services utilization.

BACKGROUND AND OBJECTIVES: Pathological gambling often co-occurs with other psychiatric disorders. Gender differences in treatment-seeking behaviors among patients with pathological gambling diagnosis remain poorly understood. This study assessed gender differences in healthcare services utilization in patients seeking treatment for pathological gambling, substance use, and mental health co-occurring conditions. METHODS: Study data were derived from a representative sample of the Massachusetts All Payers Claims Database for the period 2009-2013. Descriptive analyses were performed by gender using group t-tests and Pearson's chi-square tests. Bootstrap analysis was used to account for skewed distribution of healthcare services utilization data. Multiple linear regressions were used to evaluate the association between healthcare services utilization and gender while controlling for patient's age, county, and ICD-9-CM diagnosis codes. RESULTS: Over two-thirds of the patients were males. Moreover, two in five patients seeking treatment had pathological gambling as principal or primary diagnosis. Females had a significantly greater number of three or more co-occurring psychiatric conditions than males. Having a diagnosis of episodic mood disorder, neurotic disorder, or adjustment reaction significantly increased the utilization of healthcare services for both genders. Females had a greater utilization of healthcare services than males for the same psychiatric diagnosis. DISCUSSION AND CONCLUSIONS: Healthcare services utilization significantly varies by gender and type of mental health and substance use diagnosis. There are significant differences by gender in the utilization of healthcare services for the same psychiatric disorders. SCIENTIFIC SIGNIFICANCE: There is a need to address gender differences in psychiatric conditions and their related healthcare needs. (Am J Addict 2019;28:9-15).

Driving and riding under the influence of recent marijuana use: Risk factors among a racially diverse sample of young adults.

Driving (DUIM) and riding (RUIM) with a driver under the influence of marijuana increases crash risk. This study assessed risk factors for DUIM and RUIM among ethnically diverse young adults. Randomly selected individuals were surveyed. Multivariable regression was used to assess risk factors associated with DUIM and RUIM. Participants (N = 335, response rate = 34.9%) were 33.7% White non-Hispanic. Reported DUIM and RUIM was not statistically significant by race/ethnicity. Frequency of marijuana use was significantly associated with greater risk of DUIM. Peer marijuana use was associated with greater risk of RUIM. Public health efforts to target social norms around marijuana-impaired driving are warranted.

Cost-effectiveness analysis of metformin+dipeptidyl peptidase-4 inhibitors compared to metformin+sulfonylureas for treatment of type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D. METHODS: A Markov model was developed with four health states, 1 year cycle, and a 25-year time horizon. Clinical and cost data were collected from previous studies and other readily available secondary data sources. The incremental cost-effectiveness ratio (ICER) was estimated from the US third party payer perspective. Both, costs and outcomes, were discounted at a 3% annual discount rate. One way and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainty on the base-case results. RESULTS: The discounted incremental cost of metformin+DPP-4i compared to metformin+SU was $11,849 and the incremental life-years gained were 0.61, resulting in an ICER of $19,420 per life-year gained for patients in the metformin+DPP-4i treatment pathway. The ICER estimated in the probabilistic sensitivity analysis was $19,980 per life-year gained. Sensitivity analyses showed that the results of the study were not sensitive to changes in the parameters used in base-case. CONCLUSIONS: The metformin+DPP-4i treatment pathway was cost-effective compared to metformin+SU as a long-term second-line therapy in the treatment of T2D from the US health care payer perspective. Study findings have the potential to provide clinicians and third party payers valuable evidence for the prescription and utilization of cost-effective second-line therapy after metformin monotherapy failure in the treatment of T2D.

The patient-centered medical home model: healthcare services utilization and cost for non-elderly adults with mental illness.

BACKGROUND: The patient-centered medical home (PCMH) model is designed to improve health outcomes while containing the cost of care. However, the evidence is inconclusive. AIMS: The aim of this study was to examine the associations between receipt of care consistent with the PCMH and healthcare services utilization and expenditures for non-elderly adults with mental illness in the USA. METHOD: A surveillance study was conducted using self-reported data for 6908 non-elderly adults with mental illness participating in the 2007-2012 Medical Expenditure Panel Survey. Healthcare services utilization and expenditures were compared for study participants who received care consistent with the PCMH, participants with a non-PCMH usual source of care (USC), and participants without a USC. RESULTS: Differences in utilization and expenditures between participants who received care consistent with the PCMH and participants who had a non-PCMH USC were not statistically significant for any healthcare services category. CONCLUSIONS: Receipt of care consistent with the PCMH was not significantly associated with differences in healthcare services utilization or expenditures compared to having a non-PCMH USC. Research assessing whether the PCMH is cost-effective for non-elderly adults with mental illness is needed.

Changes in the utilization of osteoporosis drugs after the 2010 FDA bisphosphonate drug safety communication.

INTRODUCTION: In October 2010, the US Food and Drug Administration (FDA) issued a safety communication regarding the risks of atypical fractures of the femur, with bisphosphonates drugs. This study evaluated the impact of the bisphosphonates FDA safety communication on the utilization of osteoporosis medications in Medicaid programs. METHODS: Osteoporosis drugs utilization data from the July 2006 to June 2014 were extracted from the national Summary Files from the Medicaid State Drug Utilization Data maintained by the Centers for Medicare & Medicaid Services (CMS). We performed an interrupted time series analyses to evaluate trends in utilization of osteoporosis drugs before and after the 2010 FDA safety commination. RESULTS: Time-series analyses of osteoporosis drug utilization in Medicaid program revealed a significant downward trend associated with the 2010 FDA bisphosphonates safety communication. Before the FDA safety communication was issued, the utilization rate was slightly decreased between 2006 and 2010. In the year following the FDA safety communication the bisphosphonate DDDs per 1000 beneficiaries of fell 22% yearly until the end of study period. CONCLUSIONS: The 2010 FDA bisphosphonates safety communication appeared to have influenced Osteoporosis utilization in Medicaid recipients. The 2010 FDA bisphosphonates safety communication was associated with a significant reduction in the utilization of bisphosphonates in the Medicaid program.

Gambling involvement indicative of underlying behavioral and mental health disorders.

BACKGROUND AND OBJECTIVES: In spite of increased gambling opportunities, risk factors associated with recreational gambling remain poorly understood. This study assessed behavioral risk factors associated with frequency of recreational gambling. METHODS: Data were derived from the 2013 Massachusetts Behavioral Risk Factor Surveillance System. Gambling frequency was divided into two or more times per week, 1-4 times a month, less than 10 times in total, and not at all. Health risk behaviors included smoking, drinking, obesity, seat belt use, and sleep patterns. Multivariate logistic regression was used to assess relationships between overall gambling participation and gambling frequency and behavioral risk behaviors. Final analytical sample included 3,988 survey respondents. Statistical analyses were performed using STATA. RESULTS: Significant differences exist in the socio-demographic characteristics of recreational gamblers. Highest gambling frequency is associated with increased odds of alcohol consumption (ie, having at least one alcohol drink during the past 30 days) (OR 1.9; p < .05), binge drinking (ie, having five or more alcohol drinks at least once during the past 30 days) (OR 3.7; p < .001), and tobacco use (ie, having smoked at least 100 cigarettes in a lifetime) (OR 3.4; p < .001). The odds of having fourteen days of poor mental health are twofold for recreational gamblers who gamble two or more times per week (OR 2.2; p < .05). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Differing behavioral and mental health risk factors emerge among recreational gamblers by gambling frequency. Gambling frequency may be a better proxy for assessing the risk of developing gambling related behavioral disorders than overall endorsement of gambling participation.

Associations between the patient-centered medical home and preventive care and healthcare quality for non-elderly adults with mental illness: A surveillance study analysis.

BACKGROUND: Patient-centered medical homes (PCMHs) may improve outcomes for non-elderly adults with mental illness, but the extent to which PCMHs are associated with preventive care and healthcare quality for this population is largely unknown. Our study addresses this gap by assessing the associations between receipt of care consistent with the PCMH and preventive care and healthcare quality for non-elderly adults with mental illness. METHODS: This surveillance study used self-reported data for 6,908 non-elderly adults with mental illness participating in the 2007-2012 Medical Expenditure Panel Survey. Preventive care and healthcare quality measures included: participant rating of all healthcare; cervical, breast, and colorectal cancer screening; current smoking; smoking cessation advice; flu shot; foot exam and eye exam for people with diabetes; and follow-up after emergency room visit for mental illness. Multiple logistic regression models were developed to compare the odds of meeting preventive care and healthcare quality measures for participants without a usual source of care, participants with a non-PCMH usual source of care, and participants who received care consistent with the PCMH. RESULTS: Compared to participants without a usual source of care, those with a non-PCMH usual source of care had better odds of meeting almost all measures examined, while those who received care consistent with the PCMH had better odds of meeting most measures. Participants who received care consistent with the PCMH had better odds of meeting only one measure compared to participants with a non-PCMH usual source of care. CONCLUSIONS: Compared with having a non-PCMH usual source of care, receipt of care consistent with the PCMH does not appear to be associated with most preventive care or healthcare quality measures. These findings raise concerns about the potential value of the PCMH for non-elderly adults with mental illness and suggest that alternative models of primary care are needed to improve outcomes and address disparities for this population.

OSTEOPOROSIS DRUGS MARKETED IN THE UNITED STATES: GENERIC COMPETITION, PRICING STRUCTURE, AND DISPERSION AMONG PAYERS.

BACKGROUND: Despite the cost of pharmaceuticals, studies assessing prices of osteoporosis drugs are lacking. This study examined trends in prices of osteoporosis drugs in the United States in the period 1988-2014, assessed pricing structure of osteoporosis drugs, and evaluated price trends before and after generic drugs market entry. METHODS: Data were derived from the U.S. Food and Drug Administration, the RedBook, the Centers for Medicare & Medicaid Services, and the Federal Supply Schedule (FSS). Descriptive statistics and segmented linear regression analyses were performed. RESULTS: In the period 1988-2014, osteoporosis drug prices increased faster than the inflation. The average wholesale price (AWP) of generic products at market entry represented 90 percent of the AWP for the corresponding brand. Prices of brand products continued to increase after generic entry. Drug prices showed a significant variation when compared with the brand AWP. The brand wholesale acquisition cost (WAC) was typically set at 83.3 percent of the AWP. Community pharmacies acquired osteoporosis brand drugs at a median of 80.5 percent of the brand AWP. Significant reductions in brand AWP were observed for Medicare Part B (78.5 percent of the brand AWP), generic National Average Drug Acquisition Cost (33.7 percent), and FSS (22.5 percent). CONCLUSIONS: There are significant differences in the manufacturer prices, pharmacy acquisition costs and reimbursement rates of osteoporosis drugs. Pharmaceutical companies listed prices are higher than the pharmacy actual estimated acquisitions costs, and the prices used for reimbursement to providers. Generic drugs entry significantly drives down prices; still, prices of branded drugs facing generic competition continued to increase after generic market entry.

Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals?

INTRODUCTION: The US Food and Drug Administration (FDA) priority review process applies to a drug that is considered a significant improvement over the available alternatives. The European Medicines Agency (EMA) accelerated approval applies to a product that is of major public health interest. This study assessed differences in the characteristics of priority review new molecular entities and new therapeutic biologic products approved by the FDA and the EMA. METHODS: This study includes regulatory information on drug applications, approvals, indications, and orphan designations of all priority review drugs approved by the FDA and the EMA in the period 1999-2011. Descriptive statistics, t-tests, and chi-squared and Wilcoxon tests were performed. RESULTS: Overall, 100 FDA priority review new molecular entities and new therapeutic biologics were approved by both agencies; 87.0% of the products were first approved by the FDA. The average FDA review time (9.2 ± 8.4 months) was significantly lower than the EMA average review time (14.6 ± 4.0 months) (p < 0.0001). The FDA and the EMA granted orphan designation to 43.0% and 33.0%, respectively, of the applications. There were differences in the administration route (1.0% of all products), dosage (8.0%), strength (23%), posology (51.0%), indications (30.0%), restrictions of use (52.0%), limitations of use (19.0%), and outcomes limitations (28.0%) approved by both regulatory agencies. CONCLUSION: Significant differences exist in the characteristics of the priority review drugs approved by the FDA and the EMA. Harmonization of the US and European regulatory frameworks may facilitate timely approval of pharmaceutical products.

The US healthcare workforce and the labor market effect on healthcare spending and health outcomes.

The healthcare sector was one of the few sectors of the US economy that created new positions in spite of the recent economic downturn. Economic contractions are associated with worsening morbidity and mortality, declining private health insurance coverage, and budgetary pressure on public health programs. This study examines the causes of healthcare employment growth and workforce composition in the US and evaluates the labor market's impact on healthcare spending and health outcomes. Data are collected for 50 states and the District of Columbia from 1999-2009. Labor market and healthcare workforce data are obtained from the Bureau of Labor Statistics. Mortality and health status data are collected from the Centers for Disease Control and Prevention's Vital Statistics program and Behavioral Risk Factor Surveillance System. Healthcare spending data are derived from the Centers for Medicare and Medicaid Services. Dynamic panel data regression models, with instrumental variables, are used to examine the effect of the labor market on healthcare spending, morbidity, and mortality. Regression analysis is also performed to model the effects of healthcare spending on the healthcare workforce composition. All statistical tests are based on a two-sided [Formula: see text] significance of [Formula: see text] .05. Analyses are performed with STATA and SAS. The labor force participation rate shows a more robust effect on healthcare spending, morbidity, and mortality than the unemployment rate. Study results also show that declining labor force participation negatively impacts overall health status ([Formula: see text] .01), and mortality for males ([Formula: see text] .05) and females ([Formula: see text] .001), aged 16-64. Further, the Medicaid and Medicare spending share increases as labor force participation declines ([Formula: see text] .001); whereas, the private healthcare spending share decreases ([Formula: see text] .001). Public and private healthcare spending also has a differing effect on healthcare occupational employment per 100,000 people. Private healthcare spending positively impacts primary care physician employment ([Formula: see text] .001); whereas, Medicare spending drives up employment of physician assistants, registered nurses, and personal care attendants ([Formula: see text] .001). Medicaid and Medicare spending has a negative effect on surgeon employment ([Formula: see text] .05); the effect of private healthcare spending is positive but not statistically significant. Labor force participation, as opposed to unemployment, is a better proxy for measuring the effect of the economic environment on healthcare spending and health outcomes. Further, during economic contractions, Medicaid and Medicare's share of overall healthcare spending increases with meaningful effects on the configuration of state healthcare workforces and subsequently, provision of care for populations at-risk for worsening morbidity and mortality.

Medicaid provisions and the US mental health industry composition.

BACKGROUND: Medicaid is the largest payer for mental health (MH) services. AIMS: This study examines associations between Medicaid provisions and the MH industry composition. METHODS: Medicaid data derived from the Centers for Medicare and Medicaid Services. MH facility gross payroll and occupational employment data derived from the Bureau of Labor Statistics. State fixed-effects regression models are performed to examine associations. RESULTS: In the 1999-2009 period, per-capita gross payroll gains are largest for residential MH and substance abuse (SA) facilities and MH practitioner offices, followed by MH clinics and physician offices. Likewise, occupational employment gains per 100 000 people are largest for MH and SA social workers and MH counselors, followed by psychiatrists and psychologists. The Medicaid beneficiary rate is related with gross payroll gains at residential MH and SA facilities (p < 0.001) and MH clinics (p < 0.001), and with employment gains for MH and SA social workers (p < 0.001) and MH counselors (p < 0.001). Smaller effect sizes exist with MH physician offices (p < 0.05) and psychiatric hospitals' (p < 0.01) gross payroll. No statistically significant relationship exists between the Medicaid beneficiary rate and psychiatrist and psychologist employment. CONCLUSION: Medicaid provisions are related with the MH industry composition. An imbalanced MH industry may lead to inadequate management of MH disorders.

Analysis of US Food and Drug Administration new drug and biologic approvals, regulatory pathways, and review times, 1980-2022.

U.S. laws enacted since 1983 have aimed to enhance the development and marketing of new pharmaceutical products. We thoroughly characterized all new molecular entities, therapeutic biologics, and gene and cell therapies approved by the US Food and Drug Administration (FDA) during the period 1980-2022 in the context of these laws and regulations. Throughout the study period, the FDA approved 1355 new pharmaceutical products. The median FDA review time decreased from 26.6 months prior to the Prescription Drug User Fee Act (1992), which authorized the FDA to collect fees from drug companies to 9.9 months after the Food and Drug Administration Safety and Innovation Act (2012), which created new designations that eliminated the requirement for evidence of added therapeutic benefit for FDA expedited drug review. The greatest increase in approvals occurred in antineoplastic and immunomodulating drugs, biologics, and orphan drugs. More than half of new drug approvals benefited from regulatory designations and pathways that did not require addressing unmet medical needs or demonstrating therapeutic benefit over available alternatives. The legislative goal of bringing more drugs to the market faster has been achieved. Further studies are needed to determine the therapeutic value to patients of new drugs approved using expedited approval pathways.

Healthcare cost of type 1 diabetes mellitus in new-onset children in a hospital compared to an outpatient setting.

BACKGROUND: Type 1 diabetes is among the most prevalent chronic childhood diseases in the US. Initial type 1 diabetes management education and care can take place in different clinical settings. This study assessed metabolic outcomes (i.e. hemoglobin A1C), healthcare utilization and costs among new-onset type 1 diabetic children who received initial diabetes education and care in a hospital compared to those children in an outpatient pediatric endocrinology clinic. METHODS: A retrospective cross-sectional study was conducted from the payer's perspective. New-onset type 1 diabetic children, aged 1-18, presented at Baystate Children's Hospital (Massachusetts) from 2008-2009 were included in the study if lab test confirmed diagnosis and there was one year of follow-up. Inpatients spent at least one night in the hospital during a 10-day diagnosis period and received all or part of diabetes education there. Outpatients were diagnosed and received all diabetes education in a pediatric endocrinology clinic. Metabolic outcomes were measured at diagnosis and at one year post-diagnosis. Healthcare charges and electronic medical records data were reviewed from 2008-2010. Healthcare costs components included diagnostic test, pediatric, endocrinology and hospitalists care, critical and emergency care, type 1 diabetes related supplies, prescription drugs, and IV products. RESULTS: Study sample included 84 patients (33 inpatient and 51 outpatients). No statistically significant differences in patient demographic characteristics were found between groups. There were no statistically significant differences in metabolic outcomes between groups. Total cost at one year post-diagnosis per new-onset type 1 diabetic child was $12,332 and $5,053 in the inpatient and outpatient groups, respectively. The average healthcare cost for pediatric endocrinology care was $4,080 and $3,904 per child in the inpatient and outpatient groups, respectively. CONCLUSION: Provision of initial type 1 diabetes education and care to new-onset non-critically ill children in a hospital setting increases healthcare costs without improving patient's glycemic control in the first year post-diagnosis.

Changes in FDA enforcement activities following changes in federal administration: the case of regulatory letters released to pharmaceutical companies.

BACKGROUND: The United States (US) Food and Drug Administration (FDA) is responsible for the protection of the public health by assuring the safety, effectiveness and security of human drugs and biological products through the enforcement of the Federal Food, Drug and Cosmetic Act (FDCA) and related regulations. These enforcement activities include regulatory letters (i.e. warning letters and notice of violation) to pharmaceutical companies. A regulatory letter represents the FDA's first official notification to a pharmaceutical company that the FDA has discovered a product or activity in violation of the FDCA.This study analyzed trends in the pharmaceutical-related regulatory letters released by the FDA during the period 1997-2011 and assessed differences in the average number and type of regulatory letters released during the last four federal administrations. METHODS: Data derived from the FDA webpage. Information about the FDA office releasing the letter, date, company, and drug-related violation was collected. Regulatory letters were classified by federal administration. Descriptive statistics were performed for the analysis. RESULTS: Between 1997 and 2011 the FDA released 2,467 regulatory letters related to pharmaceuticals. FDA headquarters offices released 50.6% and district offices 49.4% of the regulatory letters. The Office of Prescription Drug Promotion released the largest number of regulatory letters (850; 34.5% of the total), followed by the Office of Scientific Investigations (131; 5.3%), and the Office of Compliance (105; 4.3%). During the 2nd Clinton Administration (1997-2000) the average number of regulatory letters per year was 242.8 ± 45.6, during the Bush Administration (2001-2008) it was 120.4 ± 33.7, and during the first three years of the Obama administration (2009-2011) it was 177.7.0 ± 17.0. The average number of regulatory letters released by the Office of Prescription Drug Promotion also varied by administration: Clinton (122.3 ± 36.4), Bush (29.5 ± 16.2) and Obama (41.7 ± 11.1). CONCLUSIONS: Most regulatory letters released by FDA headquarters were related to marketing and advertising activities of pharmaceutical companies. The number of regulatory letters was highest during the second Clinton administration, diminished during the Bush administrations, and increased again during the Obama administration. A further assessment of the impact of changes in federal administration on the enforcement activities of the FDA is required.