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Patent applications filed after a New Drug Application (NDA) is approved are uncommon and do not appear to substantially delay approval of generic drugs in most cases. [ABSTRACT FROM AUTHOR]

Background: Direct-to-consumer (DTC) pharmacies sell generic prescription drugs, often at lower prices than traditional retail pharmacies; however, not all drugs are available, and prices vary. Objective: To determine the availability and cost of generic drugs at DTC pharmacies. Design: Cross-sectional study. Setting: Five national DTC pharmacies in April and May 2023. Participants: Each qualifying form of 100 generic drugs with the highest cost-per-patient (expensive) and the 50 generic drugs with the highest number of patients (common) in Medicare Part D in 2020 Main Measures: Availability of these drugs and the lowest DTC pharmacy price for a standardized drug strength and supply (e.g., 30 pills), compared to GoodRx retail pharmacy prices. Key Results: Of the 118 expensive generic dosage forms, 94 (80%) were available at 1 or more DTC pharmacies; out of 52 common generic dosage forms, 51 (98%) were available (p < 0.001). Of the 88 expensive generics available in comparable quantities and strengths across pharmacies, 42 (47%) had the lowest cost at Amazon, 23 (26%) at Mark Cuban Cost Plus Drug Company, 13 (14%) at Health Warehouse, and 12 (13%) at Costco; for 51 common generic formulations, 16 (31%) had the lowest cost at Costco, 14 (27%) at Amazon, 10 (20%) at Walmart, 6 (12%) at Health Warehouse, and 5 (10%) at Mark Cuban Cost Plus Drug Company. For the 77 expensive generics with available GoodRx retail pharmacy prices, the median cost savings at DTC pharmacies were $231 (95% CI, $129–$792) or 76% (IQR, 53–91%); for 51 common generics, savings were $19 (95% CI, $10–$34) or 75% (IQR, 67–83%). Conclusions: Many of the most expensive generic drugs are unavailable at direct-to-consumer pharmacies. Meanwhile, less expensive, commonly used generics are widely available, but drug prices vary by pharmacy and savings are modest, requiring patients to shop around for the lowest cost. [ABSTRACT FROM AUTHOR]

Introduction: Lenalidomide, pomalidomide, and thalidomide are effective treatments for multiple myeloma but are teratogenic. To mitigate this risk, the US Food and Drug Administration (FDA) required risk evaluation and mitigation strategy (REMS) programs for these drugs, which include pregnancy testing among women of childbearing potential—twice before initiation, weekly in the first month on treatment, and every 2–4 weeks thereafter. Objective: We evaluated dispensing trends of lenalidomide, pomalidomide, and thalidomide and assessed adherence to REMS pregnancy testing requirements among at-risk patients taking these drugs. Methods: Using three US health insurance claims databases (Optum Clinformatics® [2004–2020], Merative Marketscan [2003–2019], and Medicaid [2000–2018]), we assessed monthly use of the drugs, patient characteristics and treatment persistence among drug initiators, and claims-based evidence for adherence to pregnancy testing requirements among initiators with child-bearing potential. Results: Lenalidomide was the most prescribed agent following its approval in 2006 and through the end of the study period. A total of 48,311 lenalidomide (mean age = 59 years [standard deviation (SD) = 16]), 17,550 thalidomide (mean age = 65 years [SD = 12]), and 6560 pomalidomide initiators (mean age = 65 years [SD = 11]) were identified; 45% of initiators of each drug were women. Among initiators under follow-up on day 90, 70% were still on therapy. Initiators of childbearing potential comprised 3% (N = 1,920) of all initiators; among this cohort, 12% had evidence in claims data of two pregnancy tests before initiation, and 9% with at least 33 days of follow-up of four tests during the first month of treatment. By contrast, 52% who received a refill had claims-based evidence of a pregnancy test within 7 days of dispensing. Conclusion: Although most patients who initiated lenalidomide, pomalidomide, and thalidomide were not of child-bearing potential, further investigation into actual non-adherence to pregnancy testing is needed. [ABSTRACT FROM AUTHOR]

Background: Originator drug manufacturers use several strategies to delay generic competition in the USA, but it remains unclear whether this results in longer market exclusivity compared to other countries. Objectives: We sought to understand how drug market exclusivity lengths vary between the USA and two comparable countries. Methods: We focused on drugs approved within 2 years of each other in the USA, France, and Australia from 1995 to 2005, and we compared the lengths of exclusivity from marketing approval through first generic competition or June 2023 using Kaplan–Meier analyses. Results: Among 165 drugs in common between the USA and France, the median length of exclusivity was slightly longer in France (15.0 years, interquartile range [IQR]: 13.0–19.6) than the USA (14.5 years, IQR: 11.7–17.6). Among 100 drugs in common between the USA and Australia, the median length of exclusivity was longer in Australia (16.3 years, IQR: 13.9–22.4) than in the USA (14.4 years, IQR: 12.0–17.1). Conclusions: Market exclusivity lengths in the USA are not longer than in France and Australia. Potential reasons include the larger US market and incentives that offer transient high generic drug prices in the USA for manufacturers that successfully challenge originator market exclusivity. [ABSTRACT FROM AUTHOR]

Administrative patent review procedures are an effective way of correcting erroneously granted biologic patents and may help promote timely drug competition for the benefit of patients and the US healthcare system. [ABSTRACT FROM AUTHOR]

This document investigates the practices of the European Medicines Agency (EMA) in using independent advisors for drug approvals. The study compares the frequency and outcomes of advisory practices at the EMA to those of the US Food and Drug Administration (FDA). The findings show that the EMA consulted advisors for a minority of drug approval decisions, with a frequency and alignment similar to the FDA. The study suggests that the EMA and FDA could coordinate to identify best practices for incorporating recommendations into regulatory decision-making. [Extracted from the article]

Drug patents that are given patent term extension are important bellwether indicators for generic drug market entry. [ABSTRACT FROM AUTHOR]

Errors in the US Patent and Trademark Office’s automated program to calculate patent expiration dates could result in hundreds of millions of dollars in added costs to drug prices. [ABSTRACT FROM AUTHOR]

The USA pays more for brand-name prescription drugs than any other country and new legislation from August 2022 gives Medicare the authority to directly negotiate certain drug prices with manufacturers starting in 2026—something the federal insurer had been prohibited from doing for its prior history. As the USA prepares for negotiations, we therefore surveyed how comparable industrialized countries use statutory requirements and procedures to negotiate brand-name drug prices. Guidance documents, regulations, government and academic publications were reviewed to identify the process of negotiating drug prices in peer countries that have been cited as potential examples for US payment reform: Australia, Canada, France, Germany, and the UK. Processes for arriving at a final price for a drug generally fall under three approaches: statutory rebates, setting a maximum price, and arbitration between national (public) insurers and manufacturers. Each approach to price negotiation could be adopted by Medicare and reduce spending even if Medicare does not adopt an exclusionary or closed formulary. Much remains to be determined about how the new price negotiation authority in the USA will be implemented, and policymakers can learn from comparator countries' statutory and regulatory strategies for price negotiation. [ABSTRACT FROM AUTHOR]

Background: Drugs and high-risk medical devices are increasingly likely to receive Food and Drug Administration (FDA) approval through expedited pathways, which has implications for informed treatment consent (i.e., consent in clinical practice).Objective: To obtain expert opinion about the clinical and ethical implications of the increasing availability of new drugs and devices approved through expedited development and regulatory review pathways.Design: Qualitative study using individual semi-structured videoconference interviews.Participants: National leaders in medicine, ethics, and law (n=12) with expertise in medical product regulation, payor policymaking, bioethics, physician practice, patient advocacy, public health expertise/advocacy, clinical trials, the pharmaceutical and device industry, institutional review board oversight, and real-world evidence.Main Measures: Principal themes in 3 domains: expedited regulatory pathways, physician and patient understanding of and reliance on FDA approval, and informed treatment consent.Key Results: Respondents pointed out that more common use of expedited pathways translates to increased reliance on surrogate measures, some with uncertain clinical significance. While expedited development and review can have advantages, participants expressed worry that physicians were unaware when medical products were expedited and did not communicate about uncertainties in knowledge about new drug or device approvals effectively with patients. Many participants felt that informed treatment consent discussions about new drugs or devices should include some explanations of expedited pathways and use of surrogate measures.Conclusions: Experts identified advantages of expediting development and of FDA flexibility in applying its standards to new drugs and medical devices, but highlighted concerns that patients may not be adequately informed about the risks of shorter review times or about uncertainties in the evidence that result. There is a need to identify approaches to ensure effective clinical use of drugs and devices when approved through expedited pathways. [ABSTRACT FROM AUTHOR]

Manufacturers of brand-name nebulizer solutions have employed a variety of strategies to preserve market dominance over their products but have been less successful than manufacturers of brand-name inhalers in preventing generic competition. [ABSTRACT FROM AUTHOR]

Introduction: After the approval of a new drug, the Food and Drug Administration (FDA) may issue postmarketing requirements (PMRs), studies that the law requires manufacturers to conduct for drugs approved under certain conditions, and postmarketing commitments (PMCs), studies that the FDA and manufacturers agree should be conducted as a condition of approval. Objective: With regulators' increasing reliance on gathering important evidence after initial product approval, we sought to assess the track record of PMRs and PMCs by synthesizing information about postmarketing study completion rates, timeliness, study types, and results reporting. Methods: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Studies published in academic journals or government reports that reported original data about the characteristics of PMRs or PMCs were included. Studies of post-approval trial mandates issued by regulators outside the USA were excluded, as were those that addressed post-approval research without mentioning either PMCs or PMRs or a specific approval pathway associated with statutorily required PMRs. Two investigators independently screened and extracted data from studies and reports. Data sources included the Federal Register from 2003 to 2020, FDA backlog reviews from 2008 to 2020, PubMed from January 2006 to April 2021, and the US Government Accountability Office (GAO) database for reports from January 2006 to April 2021. PMR/PMC characteristics (e.g., completion rates, timeliness, results reporting, outcomes) were not meta-analyzed due to the heterogeneity in study designs. Results: Twenty-seven peer-reviewed articles from PubMed, five GAO reports, 17 annual Federal Register notices, and 12 annual backlog reviews were included. Among the 27 studies, 13 reviewed PMRs and PMCs, one reviewed only PMCs, and 13 reviewed only PMRs. A majority of new drugs were approved with at least one PMR or PMC. PMCs were completed at higher rates than PMRs, although delays were common and neither was found to be completed more than two-thirds of the time. Over two-thirds of PMRs and PMCs reported their findings in publications and trial registries. Over half of PMCs and PMRs produced novel information for clinical practice or leading to regulatory action, such as confirmation of benefit or a labeling change. Conclusion: PMRs and PMCs are common for new drugs and can lead to worthwhile outcomes, but are often delayed or incomplete. Greater attention is needed to timely completion, improving transparency of findings, and ensuring that PMRs and PMCs produce optimally useful information for prescribers and patients. [ABSTRACT FROM AUTHOR]

The large number of biologic drug patents in the United States has contributed to delays in biosimilar availability. [ABSTRACT FROM AUTHOR]

Medicaid Program; Establishing Minimum Standards in Medicaid State Drug Utilization Review (DUR) and Supporting Value-Based Purchasing (VBP) for Drugs Covered in Medicaid, Revising Medicaid Drug Rebate and Third Party Liability (TPL) Requirements. Under the Medicaid Drug Rebate Program, drug manufacturers ordinarily pay a rebate to Medicaid for price increases exceeding inflation. Medicaid Program; Establishing Minimum Standards in Medicaid State Drug Utilization Review (DUR) and Supporting Value-Based Purchasing (VBP) for Drugs Covered in Medicaid, Revising Medicaid Drug Rebate and Third Party Liability (TPL) Requirements. [Extracted from the article]

Introduction: Since 2007, the US Food and Drug Administration has had the authority to require risk evaluation and mitigation strategy (REMS) programs for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Such programs can include requirements for patient monitoring, restrictions on dispensing or administration, and physician and pharmacy training and certification. However, there has been only scattered evidence on the impact of REMS programs on informed decision making, medication access, or patient outcomes. Objective: The objective of this article was to describe a study that researchers at Brigham and Women's Hospital and Harvard Medical School will conduct in partnership with the Food and Drug Administration's Office of Surveillance and Epidemiology to investigate systematically how REMS programs have operated in practice. Methods: Investigations include health insurance claims-based analyses to understand patterns of drug use, adherence to safety requirements, and patient outcomes under REMS programs; surveys and interviews to understand physician and patient experiences with REMS; and REMS program material-based and interview-based analyses to understand the effectiveness of risk communication in REMS programs. Conclusions: These research activities will evaluate the performance of REMS programs, provide information on the benefits and burdens to patients and healthcare providers, and generate recommendations for actionable steps to improve REMS programs overall. [ABSTRACT FROM AUTHOR]

Modified versions of existing drugs can substantially increase costs for patients and the health care system if the new version does not offer meaningful clinical improvement. [ABSTRACT FROM AUTHOR]

Introduction: Risk evaluation and mitigation strategy (REMS) programs are intended to improve safe use of US Food and Drug Administration-approved drugs. However, controversy exists over whether they consistently accomplish this goal.Objective: We aimed to assess how initiation of the erythropoiesis stimulating agents (ESAs) darbepoetin alfa and epoetin alfa changed following implementation and enforcement (following a 1-year post-implementation grace period) of a prominent REMS program warning physicians against use in cancer patients with hemoglobin above 10 g/dL.Methods: Using claims data from a large US commercial insurance company, we conducted interrupted time-series analyses of darbepoetin alfa and epoetin alfa initiation among adult cancer patients in the 12 months before REMS program implementation, after REMS program implementation, and after REMS program enforcement. We also evaluated differences in inappropriate initiation (hemoglobin tests all above 10 g/dL in the prior month) between the periods.Results: In total, we identified 3456 darbepoetin alfa initiators and 2632 epoetin alfa initiators. Over the study period, the monthly number of initiators per 100,000 patients with cancer fell from 119 to 32 for darbepoetin alfa and from 82 to 34 for epoetin alfa. However, non-significant post-REMS program implementation level and slope changes per 100,000 adult patients with cancer were observed for darbepoetin alfa (level 0.03 [95% confidence interval (CI) -14.98 to 15.05]; slope 1.94 [95% CI -0.22 to 4.10]) and epoetin alfa (level -4.10 [95% CI -16.85 to 8.65]; slope -0.52 [95% CI -2.35 to 1.32]). Non-significant post-REMS program enforcement level and slope changes were also seen for both drugs (darbepoetin alfa level 1.58 [95% CI -0.58 to 3.74, slope -0.28 [95% CI -15.29 to 14.73]; epoetin alfa level 1.58 (95% CI -0.26 to 3.42], slope 5.74 [95% CI -7.01 to 18.49]). Finally, non-significant changes in inappropriate darbepoetin alfa (60% vs. 53% vs. 57%, p = 0.68) and epoetin alfa (53% vs. 53% vs. 46%, p = 0.41) initiation were observed between the three study periods.Conclusion: REMS program implementation and enforcement were not associated with significant changes in ESA initiation, adding to concerns over the degree to which certain REMS programs enhance patient safety. [ABSTRACT FROM AUTHOR]

Additional changes could make the registries of drug patents published by the FDA, called the Orange and Purple Books, more useful and reduce barriers to effective competition from generic and biosimilar drugs. [ABSTRACT FROM AUTHOR]

Abbreviated regulatory approval pathways for biosimilars were created to accommodate intellectual property protection, foster competition and lower drug prices, but their success in achieving these goals has been mixed. [ABSTRACT FROM AUTHOR]

Yet, we found that brand-name Percocet (9% of all brand-name oxycodone-acetaminophen prescriptions) and Vicodin (28% of all brand-name hydrocodone-acetaminophen prescriptions) continued to be widely dispensed despite the existence of interchangeable generic versions. Graph: Figure 1 State-level variation in generic proportions of oxycodone-acetaminophen tablet and capsule opioid formulations and hydrocodone-acetaminophen tablet and capsule opioid formulations, 1991 to 2018. RESULTS Ten brand-name formulations containing oxycodone-acetaminophen and 19 containing hydrocodone-acetaminophen were prescribed in Medicaid during the study period. [Extracted from the article]

Introduction: Clinical practice guidelines recommend co-prescribing naloxone to patients at high risk of opioid overdose, but few such patients receive naloxone. High costs of naloxone may contribute to limited dispensing.Objective: The aim of this study was to evaluate rates and costs of dispensing naloxone to patients receiving opioid prescriptions and at high risk for opioid overdose.Methods: Using claims data from a large US commercial insurance company, we conducted a retrospective cohort study of new opioid initiators between January 2014 and December 2018. We identified patients at high risk for overdose defined as a diagnosis of opioid use disorder, prior overdose, an opioid prescription of ≥ 50 mg morphine equivalents/day for ≥ 90 days, and/or concurrent benzodiazepine prescriptions.Results: Among 5,292,098 new opioid initiators, 616,444 (12%) met criteria for high risk of overdose during follow-up, and, of those, 3096 (0.5%) were dispensed naloxone. The average copayment was US$24.83 for naloxone (standard deviation [SD] 67.66) versus US$9.74 for the index opioid (SD 19.75). The average deductible was US$6.18 for naloxone (SD 27.32) versus US$3.74 for the index opioid (SD 25.56), with 94% and 88% having deductibles of US$0 for their naloxone and opioid prescriptions, respectively. The average out-of-pocket cost was US$31.01 for naloxone (SD 73.64) versus US$13.48 for the index opioid (SD 34.95).Conclusions: Rates of dispensing naloxone to high risk patients were extremely low, and prescription costs varied greatly. Since improving naloxone's affordability may increase access, whether naloxone's high cost is associated with low dispensing rates should be evaluated. [ABSTRACT FROM AUTHOR]

Because clinical trials conducted for US Food and Drug Administration (FDA) approval occur in carefully monitored settings and often have strict inclusion criteria for participation, new information about drug safety is commonly discovered once a medication is FDA approved and used by larger numbers of patients. The FDA issues Drug Safety Communications when new information arises about the safety of marketed drugs that may change decision making by healthcare providers and patients. Since their inception, over 250 Drug Safety Communications have been issued alerting consumers and prescribers in the USA about safety risks related to prescription and over-the-counter medications. Researchers at the Brigham and Women's Hospital in Boston in conjunction with officials from the FDA undertook a multi-modal study of the content, dissemination, and uptake of FDA messaging, focusing on two 2013 Drug Safety Communications related to zolpidem (Ambien; Sanofi, Paris, France). Traditional and social media analyses note incomplete dissemination of key DSC messages. Surveys of patients and interviews of physicians and patients suggest important limitations in patient-provider communication that have hindered sharing of safety information with patients. Finally, pharmacoepidemiologic analyses of zolpidem dispensing patterns after the Drug Safety Communications were released suggest possible opportunities for enhancing uptake of new safety knowledge that may lead to changes in clinical practice, where appropriate. [ABSTRACT FROM AUTHOR]

Background: Generic versions of a drug can vary in appearance, which can impact adherence.Objective: To assess the preferences, perceptions, and responses of patients who experienced a change in the appearance of a generic medication.Design: Cross-sectional survey of patients from a large commercial health plan.Participants: Adults receiving generic versions of lisinopril, fluoxetine, lamotrigine, or simvastatin who experienced a change in the color or shape of their pills between March 2014 and November 2015.Main Measures: Likert-scale responses to questions concerning perceptions of generic drug safety and effectiveness, reliance on and preferences for pill appearance, and responses to pill appearance changes. Multivariable logistic regression-modeled predictors of seeking advice and adjusting use following a pill appearance change.Key Results: Of 814 respondents (response rate = 41%), 72% relied on pill appearance to ensure they took the correct medication. A similar percentage wanted their pills to remain the same color (72%), shape (71%), and size (75%) upon refill, but 58% would not have paid a $1 premium on a $5 co-pay to ensure such consistency. Most respondents (86%) wanted their pharmacists to notify them about pill appearance changes, but only 37% recalled such notification; 21% thought they received the wrong medication, and 8% adjusted medication use. Younger respondents (18-33 vs. 50-57 years) were more likely to seek advice (odds ratio [OR] = 1.91; 95% confidence interval [CI],1.02-3.59), and respondents with lower household income (< $30,000 vs. > $100,000) were more likely to adjust medication use (OR = 3.40; 95% CI,1.09-10.67).Conclusions: Requiring uniform pill appearance may help increase adherence but presents challenges. Standardized pharmacy notification and education policies may be a more feasible short-term solution. [ABSTRACT FROM AUTHOR]

Introduction: Lawyer-submitted reports may have unintended consequences on safety signal detection in spontaneous adverse event reporting systems.Objective: Our objective was to assess the impact of lawyer-submitted reports primarily for one adverse event (AE) on the ability to detect a signal of disproportional reporting for another AE for the same drug in the US FDA Adverse Event Reporting System (FAERS).Methods: FAERS reports from January 2004 to September 2015 were used to estimate yearly cumulative proportional reporting ratios (PRRs) for three known drug-AE pairs—isotretinoin-birth defects, atorvastatin-rhabdomyolysis, and rosuvastatin-rhabdomyolysis—with and without lawyer-submitted reports. Isotretinoin and atorvastatin have been the subject of high-profile tort litigation regarding other AEs. A lower bound of the 95% confidence interval (CI) of one or more based on three or more reports defined a signal.Results: Cumulative PRRs met signaling criteria in all analyses. For isotretinoin, lawyer-submitted reports increased PRRs for birth defects before 2008, with the largest increase in 2006 (2.9 [95% CI 2.4-3.5] to 3.3 [95% CI 2.8-3.9]); lawyer-submitted reports decreased PRRs for birth defects after 2011, with the largest decrease in 2013 (2.2 [95% CI 2.0-2.5] to 1.9 [95% CI 1.7-2.1]). For atorvastatin, lawyer-submitted reports reduced PRRs for rhabdomyolysis after 2013, with the largest decrease in 2015 (18.0 [95% CI 17.1-19.1] to 15.4 [95% CI 14.5-16.2]). Lawyer-submitted reports had little impact on PRRs for rosuvastatin and rhabdomyolysis.Conclusions: Inclusion of lawyer-submitted reports in FAERS did not meaningfully distort known safety signals for two drugs subject to high-profile tort litigation for other AEs. [ABSTRACT FROM AUTHOR]

Introduction: Numerous initiatives over the past decade have targeted the problem of antibiotic overuse in the US; however, the cumulative impact of such initiatives upon recent patterns of use is not known.Objectives: The aims of this study were to (1) describe general trends in outpatient antibiotic use among adults over the period 2006-2015; and (2) identify rapid shifts in use during this time period as potential indicators for key events.Methods: This was an observational study set in the ambulatory setting. Patients ≥ 18 years of age were selected from the Optum Clinformatics Datamart™, a commercial insurance claims database. The outcome measures of interest were prescriptions filled/1000 enrolled individuals, by year or quarter. We used linear regression to identify trends in use over multiple years, and change-point regression to identify rapid shifts in use within individual years.Results: From 2006 to 2015, antibiotic use declined significantly, decreasing by 12% for adults younger than 65 years of age (913-807 prescriptions/1000 individuals, p = 0.0001) and by 5% for adults ≥ 65 years of age (991-943 prescriptions/1000 individuals, p = 0.018). With change-point regression, we identified a number of rapid shifts in the use of specific antibiotic classes, such as downward shifts in the use of quinolones and macrolides during the second quarter of 2008 and 2013, respectively.Conclusions: Over the period 2006-2015 outpatient use of antibiotics decreased substantially among adults. Rapid shifts in use occurring in 2008 and 2013 may reflect the presence of key drivers of change, such as abrupt changes in access to care or perceived antibiotic safety. [ABSTRACT FROM AUTHOR]

Additionally, many drugs have at least one generic competitor but fewer than the 3 or more needed to generate major price reductions.[5] Policies to address limited generic competition could possibly extend to drugs with 3 or fewer competitors as well. In recent years, several older, off-patent drugs have not attracted generic competition, allowing their manufacturers to implement substantial price increases.[1], [2] Since 2017, the Food and Drug Administration (FDA) has taken steps to encourage generic competition for these "single-source" drugs. Because Spending Dashboard data aggregate costs for drugs with multiple formulations, we excluded drugs if only one of several formulations lacked generic competition. [Extracted from the article]

In 2017, prescription drugs accounted for about one-fifth of Medicare spending, with expenditures for the Part D outpatient drug insurance program totaling $94 billion.[1] In 2016, 84% of Part D spending came from brand-name drugs, which made up 14% of prescriptions overall.[2], [3] Since a common justification for the high prices of brand-name products is that they are needed to sustain new drug development, we examined the novelty of active ingredients in the 25 brand-name drugs with the highest Medicare Part D spending in 2017, which accounted for 30% of total Part D spending that year. RESULTS Among the 27 active ingredients identified - 22 single active ingredient products, 3 combination products, and 2 products containing the same active ingredient - 11 (41%) had previously been approved by the FDA in other formulations or products (Table 1). Budesonide was first approved in the product Rhinocort and formoterol was first approved in the product Symbicort SP ‡ sp Approved on 8/24/2000, Advair Diskus was the first drug containing the combination of both fluticasone and salmeterol. [Extracted from the article]

METHODS Sixteen biosimilars of 9 originator biologics had been approved by both the FDA and the EMA by February 2019 (the infliximab biosimilar Ifixi was FDA- but not EMA-approved). FDA and EMA approvals were based on 20 and 22 clinical trials, respectively, about two-thirds of which (FDA, 65%; EMA, 64%) were phase I trials. Two were approved without a phase II or III trial: the filgrastim biosimilar Nivestym (FDA) and the pegfilgrastim biosimilar Udenyca (FDA/EMA). [Extracted from the article]

With opioid-related overdose deaths in the USA reaching 50,000 in 2017,[1] federal and state governments have struggled to respond to this growing crisis. Poisson (for relative-risks), inverse Gaussian, and Gamma distributions were used to model the relative risk of initiating a > seven-day opioid prescription, opioid duration, and MED respectively. [Extracted from the article]

Background: A run-in phase is often employed prior to randomization in a clinical trial to exclude non-adherent patients, placebo responders, active drug non-responders, or patients who do not tolerate the active drug. This may impact the generalizability of trial results.Objective: To determine if clinical outcomes differed between randomized controlled trials with run-in phases compared with randomized controlled trials of the same medication without run-in phases.Design, Participants: From 2006 to 2014, the Food and Drug Administration approved 258 new medications. Sitaglitpin, saxagliptin, linagliptin, and alogliptin were among the only drugs with a common mechanism of action that each had multiple clinical trials, some of which had run-in phases and some of which did not. We identified all published randomized controlled trials for these four medications from MEDLINE and EMBASE as well as prior systematic reviews.Main Measures: We extracted key measures of medication efficacy (reduction in hemoglobin A1C) and safety (serious adverse events) from qualifying trials. Study results were pooled for each medication using random effects meta-analysis.Key Results: We identified 106 qualifying trials for DPP4 inhibitors, of which 88 had run-in phases and 18 did not. The average run-in phase duration was 4.0 weeks (range 1-21), and 73% of run-in phases administered placebo rather than active drug. The reduction in hemoglobin A1C compared to baseline was similar for trials with and without run-in phases (0.70%, 95% confidence interval [CI] 0.65-0.75 vs 0.76%, 95% CI 0.69-0.84, p = 0.27). The proportion of patients with serious adverse events was also similar for trials with and without run-in phases (4%, 95% CI: 3-5% vs 3%, 95% CI: 1-4%, p = 0.35).Conclusion: Trials with run-in phases provided similar estimates for medication efficacy and safety compared to trials without run-in phases. Because run-in phases are costly and time-consuming, these results call their utility into question for clinical trials of short duration. [ABSTRACT FROM AUTHOR]

Introduction: The US Food and Drug Administration uses drug safety communications (DSCs) to release emerging information regarding post-market safety issues, but it is unclear the extent of awareness by patients and providers of these communications and their specific recommendations.Objective: We conducted semi-structured interviews with patients and physicians to evaluate their awareness and understanding of emerging drug safety information related to two sleep aids: zolpidem or eszopiclone.Methods: We conducted interviews with 40 patients and ten physicians recruited from a combination of insurer claims databases and online sources. We evaluated (1) sources of drug safety information; (2) discussions between patients and physicians about the two medications; (3) their knowledge of the DSC; and (4) preferences for learning about future drug safety information. Interviews were transcribed and analyzed thematically.Results: Patients cited their physicians, pharmacy inserts, and the Internet as sources of drug safety information. Physicians often referred to medical journals and online medical sources. Most patients reported being aware of information contained in the DSC summaries they were read. Almost all patients and physicians reported discussing side effects during patient-provider conversations, but almost no patients mentioned that physicians had communicated with them key messaging from the DSCs at issue: the risk of next-morning impairment with zolpidem and the lower recommended initial dose for women.Conclusions: Some risks of medications are effectively communicated to patients and physicians; however, there is still a noticeable gap between information issued by the Food and Drug Administration and patient and physician awareness of this knowledge, as well as patients' decisions to act on this information. Disseminators of emerging drug safety information should explore ways of providing user-friendly resources to patients and healthcare professionals that can update them on new risks in a timely manner. [ABSTRACT FROM AUTHOR]

As lower-cost versions of original biologic drugs made by different manufacturers, follow-on biologics offer the promise of meaningful savings for the US health care system and improved patient health outcomes through greater medication adherence. Fulfillment of this promise, however, is predicated on the prescribing of such products. Under state drug product selection laws, pharmacists may substitute prescriptions for brand name, small-molecule drugs with their generic equivalents, but will be indefinitely prohibited from substituting prescriptions for original biologics with their follow-on biologic counterparts given a lack of product-specific guidance on demonstrating interchangeability. Even when interchangeable follow-on biologics become available, they will face heightened barriers to substitution following the enactment of so-called carve-outs in several states. Data collected to date suggest that a substantial proportion of US physicians remain skeptical of follow-on biologics despite their long record of safe and effective use in Europe. Active surveillance of follow-on biologics within the US market using insurance claims databases can help address this skepticism and help answer key questions concerning the safety of switching between original and follow-on products or between different follow-on products, and of extrapolating to broader indications. Funding is needed to support such surveillance activities and to disseminate the findings to key stakeholders. [ABSTRACT FROM AUTHOR]

However, some generic drug prices have risen due to insufficient competition levels,[1], [2] and drug shortages,[3] which threatens to undermine these benefits.[4] To characterize the recent trends in the US generic-drug marketplace, we sought to examine price changes for generic drugs between 2008 and 2016. Percentage changes in drug prices from their baseline were estimated for the study-drugs in every period; categories of price change ratios were calculated by dividing the price in each period by the baseline value. Between 2008 and 2016 in a cohort of 1099 generic drugs, prices for 189 (17.2%) drugs more than doubled, while 668 (60.8%) drugs experienced a price decrease (Table 1). [Extracted from the article]

The article offers information on the financial relationships between physicians and prescription drug or medical device manufacturers remain controversial. It mentions such relationships are associated with prescription of brand-name drugs, especially those sold by the sponsoring manufacturer, over equally effective lower-cost generics; and also mentions free samples of drug are used as a marketing tool and have been linked to prescribing of high-cost brand-name drugs.

Boxed warnings-also known as "black box" warnings-can be a powerful tool in communicating drug risks to physicians and patients. The overall number of boxed warnings has grown in recent years as the US Food and Drug Administration (FDA) has approved more drugs on the basis of limited pre-marketing information and as new safety issues for marketed drugs have been identified. Two recent manufacturers' petitions to remove boxed warnings on the drugs rosiglitazone (Avandia) and varenicline (Chantix) have led to divergent FDA decisions and revealed different considerations involved in boxed warning imposition and removal. For ethical and practical reasons, the FDA is justified in applying a higher standard for boxed warning removal than for imposition, as removal of a boxed warning may have unintended effects on physician and patient behavior. However, no guidelines on boxed warning removal currently exist. To promote safe use of approved prescription drugs, the FDA should adopt a uniform and transparent process governing decisions to impose or remove boxed warnings. [ABSTRACT FROM AUTHOR]

Background: Over 84 % of all prescriptions in the US are filled as generic drugs, though in prior surveys, patients reported concerns about their quality.Objective: We aimed to survey patients' perceptions and use of generic drugs.Design: Our survey (administered August 2014) assessed patients' skepticism about generic drug safety and effectiveness and how often they requested brand-name drugs. Chi-square tests and two-sample t-tests assessed associations between patient demographics and the outcomes.Participants: Our sample frame was the CVS Advisor Panel, a national database of 124,621 CVS customers. We randomly selected 1450 patients with self-reported chronic conditions who filled at least one prescription in the prior 3 months.Main Measures: We assessed how often patients reported asking their physicians to prescribe a brand-name over a generic drug in the last year, and "generic skepticism," defined as not believing generic drugs were as safe, effective, had the same side effects, and contained the same active ingredients as brand-name drugs.Key Results: Of the 1,442 patients with valid addresses, 933 responded (65 % response rate) and 753 took the full survey. A vast majority (83 %) agreed that physicians should prescribe generic drugs when available, and 54 % said they had not asked their physicians to prescribe a brand-name drug over a generic in the past year. Most respondents considered generic drugs to be as effective (87 %) and safe (88 %) as their brand-name counterparts, and to have the same side effects (80 %) and active ingredients (84 %). Non-Caucasians were more likely than Caucasians to request a brand-name drug over a generic (56 % vs. 43 %, p < 0.01), and were also more skeptical of generic drugs' clinical equivalence (43 % vs. 29 %, p < 0.01).Conclusions: We found a substantial shift towards more patients having positive views of generic drugs, but lingering negative perceptions will have to be overcome to ensure continued cost-savings and improved patient outcomes from generic drugs. [ABSTRACT FROM AUTHOR]

Background: A brand-name version of colchicine (Colcrys) was introduced after its manufacturer conducted a clinical trial in acute gout patients, leading to higher prices for this drug.Objective: We analyzed the impact of the new single-source colchicine product on prescribing and patient health spending as well as incidence rates of potentially dangerous concomitant use of clarithromycin and cyclosporine after formal FDA approval.Design/participants: We conducted a retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed with gout or FMF.Main Measures: Among gout and FMF patients separately, we assessed linear trends in colchicine prescriptions, prescription drug costs, and total health care costs from 2009 to September 2010 (market exclusivity announced) compared to January 2011 (market exclusivity enforced) through 2012. Next, we estimated trends in co-prescription within 15 days of clarithromycin, azithromycin (indicated on the Colcrys label for use in place of clarithromycin), and cyclosporine.Key Results: Among gout patients, before Colcrys' market exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011-1.018). Following FDA action, the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992-0.999) (p < 0.001). Similarly, among FMF patients, odds of initiating colchicine changed from an increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients receiving colchicine experienced increases in average monthly prescription drug costs ($418 vs. $651, p < 0.001) and health care costs ($3,406 vs. $3,534, p < 0.001). Incidence rates of colchicine/clarithromycin co-prescription before and after FDA action did not change, while co-prescription of colchicine/cyclosporine increased after introduction of Colcrys [-0.75 monthly change in patients (95 % CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p < 0.001].Conclusions: The FDA's actions were associated with a reduction in colchicine initiation and an increase in patient spending. By contrast, we did not observe any association with improvements in avoidance of potentially dangerous co-prescriptions. [ABSTRACT FROM AUTHOR]

Generic drugs possessing the same active ingredients, dosage form, strength, route of administration, and labeling can be approved by the US Food and Drug Administration (FDA) as interchangeable with a brand-name drug without needing to repeat the formal Phase I, II, and III clinical trials conducted by the original manufacturers. In recent years, the FDA has approved several generic drugs using product-specific testing to determine therapeutic equivalence in accordance with the unique features of the particular drug. These have been used in two primary situations: (1) cases for which certain bioequivalence studies were not relevant; and (2) cases of complex molecules that may require specially tailored pharmaceutical equivalence studies. Examples include venlafaxine extended release, acarbose, vancomycin capsules, sodium ferric gluconate, salmon calcitonin nasal spray, and enoxaparin. Product-specific approaches to demonstrating therapeutic equivalence are essential to avoid delays in low-cost generic drug availability but can have important clinical implications; yet, currently, there is no formal process in place to monitor the safety and effectiveness of generic drugs approved using modified regulatory pathways. Several strategies can be used to monitor the safety and effectiveness of generic drugs approved via product-specific determinations of therapeutic equivalence. [ABSTRACT FROM AUTHOR]

Background: When the US FDA approves a new prescription drug there is still a great deal remaining to be learned about the safe and proper use of that product. When new information addressing these topics emerges post-approval, the FDA may issue a Drug Safety Communication (DSC) to alert patients and physicians. The effectiveness of the communication-how drug safety messaging conveyed in FDA DSCs changes patient or prescriber behavior-may depend on multiple factors, including the way physicians and patients learn about the information, their understanding of the issues conveyed, and their perception of the importance of the information. In 2013, the FDA issued two DSCs addressing critical new warnings related to products containing the sedative/hypnotic zolpidem.Objective: In this article, we describe a core set of research initiatives that can be used to study how zolpidem-related DSCs affected subsequent physician and patient decision making.Methods: These research initiatives include analyzing drug utilization patterns and related health outcomes; comparing zolpidem-containing products against a comparator with similar indications [eszopiclone (Lunesta)] not covered by the 2013 DSCs; and surveying patients and qualitatively evaluating the dissemination of information regarding these drugs in traditional and social-media channels.Conclusions: Using an integrated, multidisciplinary approach, we can obtain information that can be used to optimize regulatory communications by seeking to understand the impact of the information contained in FDA risk communications. [ABSTRACT FROM AUTHOR]

Strategic and legislative efforts to catalyse pharmaceutical innovation may be hampered by a lack of consensus over what characterizes an innovative drug. To help clarify this issue, we conducted an extensive survey on transformative drug development, involving ∼180 expert physicians based at 30 leading US academic medical centres, covering 15 medical specialties. In an iterative Delphi process, the survey participants narrowed a list of all new drugs approved in their fields in the past 25 years and reached consensus over those that they considered to be most transformative, which are presented in this article. Participants were also asked how various factors affected their opinion; they most often invoked the effectiveness and superiority of the drugs over existing alternatives when identifying transformative drug innovation. [ABSTRACT FROM AUTHOR]

Background: The automatic substitution of bioequivalent generics for brand-name antiepileptic drugs (AEDs) has been linked by anecdotal reports to loss of seizure control. Objective: To evaluate studies comparing brand-name and generic AEDs, and determine whether evidence exists of superiority of the brand-name version in maintaining seizure control. Data Sources: English-language human studies identified in searches of MEDLINE, EMBASE and International Pharmaceutical Abstracts (1984 to 2009). Study Selection: Randomized controlled trials (RCTs) and observational studies comparing seizure events or seizure-related outcomes between one brand-name AED and at least one alternative version produced by a distinct manufacturer. Data Extraction: We identified 16 articles (9 RCTs, 1 prospective nonrandomized trial, 6 observational studies). We assessed characteristics of the studies and, for RCTs, extracted counts for patients whose seizures were characterized as 'controlled' and 'uncontrolled'. Data Synthesis: Seven RCTs were included in the meta-analysis. The aggregate odds ratio (n?=?204) was 1.1 (95% CI 0.9, 1.2), indicating no difference in the odds of uncontrolled seizure for patients on generic medications compared with patients on brand-name medications. In contrast, the observational studies identified trends in drug or health services utilization that the authors attributed to changes in seizure control. Conclusions: Although most RCTs were short-term evaluations, the available evidence does not suggest an association between loss of seizure control and generic substitution of at least three types of AEDs. The observational study data may be explained by factors such as undue concern from patients or physicians about the effectiveness of generic AEDs after a recent switch. In the absence of better data, physicians may want to consider more intensive monitoring of high-risk patients taking AEDs when any switch occurs. [ABSTRACT FROM AUTHOR]

The article discusses a draft guidance issued by the U.S. Food and Drug Administration (FDA) to regulate in vitro diagnostic tests conducted outside of a living body to diagnose diseases. Topics include safety issues associated with laboratory-developed tests for rare diseases, developed by individual laboratories, the Clinical Laboratory Improvement Amendments Act, and the analytical and clinical validity required for premarket approval of in vitro diagnostics by the FDA.