Comorbid pathological gambling, mental health, and substance use disorders: Health-care services provision by clinician specialty

Background and aims Pathological gambling (PG) is an impulse control disorder. This study assessed the burden of co-occurring behavioral addictions and mental health disorders in treatment-seeking patients and estimated the likelihood of receiving care for these disorders by clinician specialty. Methods Study data were derived from the Massachusetts All-Payer Claims Database, a representative database, for the period 2009–2013. The sample included commercially insured adult residents of Massachusetts. Univariate and multivariate logistic regressions were used to estimate the likelihood of provision of care by clinician specialty adjusting for patient’s demographic characteristics and level of care. Bonferroni correction was applied to adjust for multiple testing. Results The study sample included 869 patients. Treatment-seeking patients who had a diagnosis of PG were mostly males (71%), aged 45–54 years (26.7%) and enrolled in a health maintenance organization (47%). The most prevalent co-occurring disorders among patients with PG as principal diagnosis were anxiety disorders (28%), mood disorders (26%), and substance use disorders (18%). PG was associated with a more than twofold likelihood of receiving care from social workers and psychologists (p  Discussion and conclusions Psychiatric and substance use disorders are prevalent among treatment-seeking pathological gamblers. The likelihood of receiving care from specialty clinicians significantly varies by clinical diagnosis and patient clinical complexity

Innovation and Competition in Advanced Therapy Medicinal Products

Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There are already ATMPs under development to address these and many other unmet medical needs (FDA, 2013; MIT NEWDIGS FoCUS Project, 2017) and for the treatment of prevalent conditions, such as cardiovascular, neurologic, and metabolic diseases

Predictors of Shortages of Opioid Analgesics in the US: Are the Characteristics of the Drug Company the Missing Puzzle Piece?

Background Shortages of opioid analgesics are increasingly common, interfere with patient care and increase healthcare cost. This study characterized the incidence of shortages of opioid analgesics in the period 2015–2019 and evaluated potential predictors to forecast the risk of shortages. Methods This was an observational retrospective study using the US Food and Drug Administration (FDA) drug shortages data. All FDA approved opioids were included in the study. Opioid analgesics were identified using the FDA National Drug Codes (NDC) and classified according to the Drug Enforcement Administration (DEA) schedule. We conducted Least Absolute Shrinkage and Selection Operator logistic regression analysis to assess direction of the association between risk of shortage and potential predictors. We used multivariable penalized logistic regression analysis to model predictors of shortages. We split the dataset into training and validation sets to evaluate the performance of the model. Findings The FDA approved 8,207 unique NDCs for opioid analgesics; 3,017 (36.8%) were in the market as of April 30, 2019 and 91(3.0%) of them were listed as in shortage by the FDA. All NDCs in shortage were schedule II opioids; 86 (94.5%) were injectable and 84 (92.3%) generics. There were 418 companies with at least one opioid NDC listed by the FDA. Three companies accounted for more than 4 in 5 of the schedule II active injectable opioids. For each unit increase in the number of prior instances of shortages of a company, the likelihood of an NDC shortage for that company increased by 3.4%. For each unit increase in number of NDCs marketed by a company, the odds of an NDC shortage for that company decreased by 1%. Conclusions In the period 2015–2019, shortages of opioid analgesics disproportionally impacted schedule II and injectable opioids. The risk of shortage of opioid analgesics significantly increased with the incidence of previous instances of shortages of a manufacturing company and decreased with the number of NDCs marketed by a company. The characteristics of the manufacturing company, rather than the number of companies, might be the missing piece to the complex puzzle of drug shortages in the US

Ethical Imperatives of Timely Access to Orphan Drugs: Is Possible to Reconcile Economic Incentives and Patients’ Health Needs?

Background More than 6,800 rare diseases and conditions have been identified in the US, which affect 25–30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the effectiveness of incentives for the development of treatments for rare diseases, and reflected on the ethical imperatives for timely access to orphan drugs. Methods Study data were derived from the Food and Drug Administration (FDA) Orange Book and the Office of Orphan Drugs Development. A search was conducted to assess literature on the ethical principles and economic incentives for the development of orphan drugs. Results In the period 1983–2015, the FDA granted 3,647 orphan drug designations and 554 orphan drug approvals. The orphan drug approvals corresponded to 438 different brand names. Cancer was the therapeutic area with the highest number of approvals. The increased number of patients with rare diseases and the growth in the cost of orphan drugs pose a significant economic burden for patients, public programs and private third party payers. Regulatory differences to qualify for orphan designation and various population thresholds employed by the FDA and the European Medicines Agency lead to further unmet health needs for patients with rare diseases and aggravate health inequities. There is no societal consensus on the population and economic thresholds, the drug effectiveness indicator(s), or the societal value to be placed for the approval and reimbursement of orphan drugs. Conclusion Orphan drug development and marketing in the US concentrate in few therapeutic areas. Despite the increase in the number of FDA approved orphan drugs, the unmet needs of patients with rare diseases evidence that the current incentives are not efficiently stimulating orphan drug development. There is need to balance economic incentives to stimulate the development and marketing of orphan drugs without jeopardizing patients’ access to treatment. Thus, aligning pharmaceutical companies’ incentives with societal budgetary constraints is necessary and the ethical imperatives of timely access to orphan drugs need to be agreed upon

Provision of Health Care Services in Canada: Challenges and Opportunities

The Canadian health care system provides comprehensive coverage of hospital and outpatient care, including therapeutic, diagnostic and preventive services. The level of coverage of services varies across the country. This study examines the key characteristics of the Canadian health and long-term care systems; presents a structured analysis of the insurance, financing and provision of health and long-term care services in Canada; describes the main challenges of the Canadian health and long-term care systems; and concludes with feasible opportunities for the Canadian health policy. Main challenges to the Canadian system are related to population ageing; prevalence of avoidable diseases caused by poor health habits; coverage and financing of long-term care services; financing of expensive new technologies and pharmaceuticals; and the shortage and unbalanced geographic distribution of health care professionals. Opportunities for the Canadian health policy are: strengthening public health policy, continuing shifting care to the ambulatory level; improving the coordination between primary care and specialist services; implementing a system-wide national human resources planning; and integrating home-based care as part of overall primary health care

Exploring the Potential for Using Drug Indications to Prevent Look-Alike and Sound-Alike Drug Errors

Background: Look-alike, sound-alike (LASA) drug names are a cause of medication errors with resulting patient harm and healthcare costs. This study assessed to which extent the use of the generic drug name, therapeutic class, health problem, and the U.S. Food and Drug Administration (FDA)-approved indications might be used to differentiate LASA drug pairs. Research design and methods: We collected information about LASA drug pairs reported by the FDA to have look-alike sound-alike similarities. To assess potential for differentiating LASA drug pairs, we compared the following drug characteristics: generic name, therapeutic class, health problem, and FDA-approved indication. Results: For the 33 FDA reported LASA drug pairs we identified a total of 432 FDA-approved indications. Using the generic name, therapeutic class, health problem and drug indication we were able to differentiate 8 (24.2%), 24 (72.7%), 25 (75.8%) and 26 (78.8%), respectively of the 33 LASA drug pairs. Using the generic name, therapeutic class, and health problem we were able to distinguish 31 (7.2%), 212 (49.1%), and 269 (62.3%), respectively of the 432 FDA-approved indications for the LASA drug pairs. Conclusions: Including the FDA-approved indication in the drug prescription may be used to differentiate LASA drug pairs and thus, prevent wrong drug medication errors

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

Postoperative Respiratory Events in Surgical Patients Exposed to Opioid Analgesic Shortages Compared to Fully Matched Patients Non-exposed to Shortages

Introduction Shortages of opioid analgesics critically disrupt clinical practice and are detrimental to patient safety. There is a dearth of studies assessing the safety implications of drug shortages. Objective We aimed to assess perioperative opioid analgesic use and related postoperative hypoxemia (oxygen saturation less than 90%) in surgical patients exposed to prescription opioid shortages compared to propensity score-matched patients non-exposed to opioid shortages. Methods We conducted a retrospective study including adult patients who underwent elective surgery at The University of California San Francisco in the period August 2018–December 2019. We conducted a Gamma log-link generalized linear model to assess the effect of shortages on perioperative use of opioids and a weighted logistic regression to assess the likelihood of experiencing postoperative hypoxemia. Results There were 1119 patients exposed to opioid shortages and 2787 matched non-exposed patients. After full matching, patients exposed to shortages used a greater mean of morphine milligram equivalents/day (146.94; 95% confidence interval 123.96–174.16) than non-exposed patients (117.92; 95% confidence interval 100.48–138.38; p = 0.0001). The estimated effect was a 1.25 (95% confidence interval 1.12–1.40; p = 0.0001) times greater use of opioids in patients exposed to opioid shortages than non-exposed patients. After full matching, a greater proportion of patients exposed to shortages (19.06%) experienced hypoxemia compared with non-exposed patients (16.91%). In addition, a greater proportion of patients exposed to opioid shortages (1.20%) experienced hypoxemia reversed by intravenous naloxone administration compared with non-exposed patients (0.44%). Conclusions Given the shortage prevalence, reliance on opioid medications, and related risk of respiratory depression, harm prevention measures remain critical to prevent postoperative complications that may compromise patients’ safety

The Landscape of Cellular and Gene Therapy Products: Cost, Approvals, and Discontinuations

Background The past 10 years witnessed a significant increase in the approval of cellular and gene therapy products worldwide. The US Food and Drug Administration (FDA) approved 3 gene therapy products within the last 4 months of 2017. The objective of this study was to examine the approval characteristics, discontinuations and cost of all cellular and gene therapy products approved worldwide. Data and Methods We conducted an electronic search of approved cell and gene therapy products from the databases of the main drug regulatory agencies including the US Food and Drug Administration, the European Medicines Agency (EMA), the Korea Ministry of Food and Drug Safety (MFDS), and Japan’s Pharmaceuticals and Medical Devices Agency, China Food and Drug Administration, Ministry of Health and Social Development-Russia, Health Canada, and the Food and Drug Administration of the Philippines. We also searched the literature using MEDLINE/PubMed, Cochrane Library, Google Scholar and EMBASE databases. Cost information from the US was derived from the Reb Book (Truven Health Analytics). Costs from Europe were derived from Health Technology Assessments and from public sector, financial news and company’s web pages. Where available, we also obtained cost for products approved in other countries from public sector, financial news and company’s web pages. All cost data were converted to USD. Results There were 52 cell and gene therapy products marketed in the world as of September 2018. Of these, 39 (75.0%) were cell therapy medicinal products and 13 (25.0%) were gene therapy medicinal products. Of the approved products, 29 (74.3%) cell and 8 (61.5%) gene therapy products were first approved in the past 10 years (2008-present). Korea had the greatest number of approved cellular therapy-19 followed by US-12, Japan -4, Europe -3 and Canada -1. While Europe had the highest number of approved gene therapies - 5 followed by US - 3, China -2 and Korea, Russia and Philippines one each. Overall, 8 (66.7%) of the approved gene therapy products were granted orphan designation. Three products approved by the EMA were withdrawn or discontinued from the market. Of them, 2 remain currently marketed in the US. Cost of treatment from Gene therapy in US ranged from $447600 to$1,020,000 while in Europe the range was $370000 to$962890. Gene therapies outside US and Europe were relatively cheaper. Cell therapies in North America had a price range from $30,370-$200,000, European cell therapies ranged from $17,658-$105,000. Conclusion In the study period, more autologous cell therapy products were approved than allogenic agents. The cost of gene and cell therapy drugs is much higher in the EU and North America in comparison to Asia. Majority of the gene therapies received orphan designation by the regulatory authorities and had conditional approvals while less than a quarter of cellular therapies received the orphan designation. Most of the gene therapies are approved for rare diseases with smaller patient population, companies find it difficult to make profits which results in market withdrawal of the therapies

Efficacy and Safety of Ciltacabtagene Autoleucel and Idecabtagene Vicleucel in Multiple Myeloma Patients

Background: Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are chimeric antigen receptor (CAR) T-cell therapies used to treat adult patients with relapsed or refractory multiple myeloma (rrMM) after at least four lines of therapy. However, no head-to-head clinical trials to compare them have been conducted. Objective: To compare between CARTITUDE-1 and KarMMa clinical trials in terms of efficacy, safety, and patient characteristics. Method: Overall response rate (ORR) and safety signals were compared using reporting odds ratios (RORs) with 95% confidence intervals (CIs) at p \u3c 0.05. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan–Meier method with a log-rank test. Patient characteristics were compared using the chi-square test. Statistical analyses were conducted using Microsoft Excel and R version 4.0.5. Results: Statistically significant differences were observed between cilta-cel and ide-cel in terms of ORR, complete response (CR), OS, and PFS (p \u3c 0.05). Partial response (PR) showed no statistically significant difference (p \u3e 0.05). Ide-cel was significantly associated with higher incidences of any Grade ≥ 3 adverse events than cilta-cel. Cilta-cel on the other hand, was significantly associated with higher incidences of leukopenia, lymphopenia, and CRS Grade 1 & 2 than ide-cel (RORs \u3e 1, p \u3c 0.05). Penta-drug refractory showed a statistically significant difference between cilta-cel and ide-cel clinical trials. Conclusion: This study found that cilta-cel is a superior treatment over ide-cel with better efficacy and less incidence of serious adverse events