Continuing trends in U.S. brand-name and generic drug competition.

OBJECTIVE: To provide updated evidence in a series of analyses of U.S. trends over the past two decades in key financial metrics for branded drugs: market exclusivity periods (MEPs, the time between launch and first generic entry) for new molecular entities (NMEs); the probability, timing and number of patent challenges under Paragraph IV of the Hatch-Waxman Act; and the intensity of generic penetration. METHODS: As previously, we used IQVIA National Sales Perspectives U.S. data to calculate MEPs for the 356 NMEs experiencing initial generic entry from 1995 through 2019, the number of generic competitors for twelve months afterward (by prior sales level), and generic shares. We calculated the probability, timing and number of Paragraph IV challengers using Abbreviated New Drug Application (ANDA) approval letters, the FDA website, public information searches, and ParagraphFour.com. RESULTS: For NMEs experiencing initial generic entry in 2017-19, the MEP was 13.0 years for drugs with sales greater than $250 million in 2008 dollars the year before generic entry (NMEs>$250 million), 14.1 years overall. One year later, brands' average unit share was 18% for NMEs>$250 million, 23% overall. Ninety-three percent of NMEs>$250 million experiencing initial generic entry faced at least one Paragraph IV challenge (2019, three-year rolling average), an average of 6.0 years after brand launch (81% and 6.3 years for all NMEs). NMEs faced an average of 6.8 and 8.9 Paragraph IV challengers per NME, for all and NMEs>$250 million, respectively (2017-19 figures). LIMITATIONS: All analyses were restricted to NMEs experiencing generic entry. CONCLUSION: The average 2017-19 MEP of 13.0 years for NMEs>$250 million has changed relatively little over the past decade and remains lower than for all NMEs (14.1 years). Paragraph IV challenges are more frequent and occur earlier for NMEs>$250 million. Generic share erosion remains high for both NME types.

Birch bark tar in early Medieval England - Continuity of tradition or technological revival?

Birch bark tar is a manufactured product with a history of production and use that reaches back to the Palaeolithic. Its sticky, water resistant and biocidal properties mean that it has a wide range of applications, for example, as a multipurpose adhesive, sealant and in medicine. Archaeological evidence for birch bark tar in the old world covers a broad geographic range from the UK to the Baltic and from the Mediterranean to Scandinavia. In the east and north of this range there is continuity of use to modern times but in western Europe and the British Isles the use of birch bark tar has generally been viewed as limited to prehistory, with gradual displacement by pine tars during the Roman period. Here, we report new finds of birch bark tar from two early Medieval sites in the east of England. Analysis by HT-GC/MS to identify the tars also revealed fatty material, possibly added to modify the tar. The different contexts of the finds point to diverse applications of the material: in one case perhaps a medicine, the other associated with a ceramic container, possibly used for processing the tar. The results present the first identification of birch bark tar from early Medieval archaeological contexts in the UK. Together they indicate a later period of use for birch bark tar in the UK than has been previously observed and raise the question of whether this indicates evidence of a longer continuity of use than hitherto recognised or a later reintroduction of the technology in the Medieval period, in which case the similarities between the find sites, both early Anglo-Saxon cemeteries with comparable assemblages of grave goods, may be significant.

Cardiac arrhythmia detection outcomes among patients monitored with the Zio patch system: a systematic literature review.

Objective: Cardiac arrhythmias can be serious and life threatening, and can impose a significant burden on healthcare systems. Recent technological advances in ambulatory electrocardiogram recorders have led to the development of unobtrusive wearable biosensors which allow physicians to study patients' continuous cardiac rhythm data collected over multiple weeks. The objective of this systematic literature review was to summarize evidence on the clinical effectiveness of the Zio 1 patch, a long-term, continuous, uninterrupted cardiac monitoring system. Methods: Findings from searches of MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, as well as grey literature, were screened by two reviewers to identify studies reporting cardiac arrhythmia detection outcomes among patients monitored with Zio for an intended duration ≥7 days. Results: Twenty-three publications (22 unique studies) were identified. The unweighted mean wear time was 10.4 days (median ranging from 5 to 14 days). The rate of arrhythmia detection increased with monitoring durations >48 h and continued to increase beyond 7 days of monitoring. Across the 22 studies, unweighted mean detection rates for atrial fibrillation (AF; n = 15), supraventricular tachycardia or supraventricular ectopy (n = 15), and ventricular tachycardia (n = 15) were 12.2%, 45.5% and 17.3%, respectively. Unweighted mean detection rates for chronic/sustained AF (n = 5) and paroxysmal AF (n = 5) were 5.6% and 23.3%, respectively. Conclusion: Findings from the review suggest that long-term, continuous, uninterrupted monitoring with Zio results in longer patient wear times and higher cardiac arrhythmia detection rates compared with outcomes reported in previous reviews of short-duration (24-48 h) cardiac rhythm recording studies.

Updated trends in US brand-name and generic drug competition.

OBJECTIVE: To provide updated evidence on US trends in: market exclusivity periods (MEPs, time between brand-name drug launch and first generic competitors) for new molecular entities (NMEs); likelihood, timing and number of Hatch-Waxman Act Paragraph IV patent challenges; and generic drug penetration. METHODS: This study used IMS Health National Sales Perspectives(TM) US data to calculate MEPs for the 288 NMEs experiencing initial generic entry between January 1995 and December 2014, the number of generic competitors for 12 months afterward (by level of annual sales prior to generic entry), and generic penetration rates. The likelihood, timing and number of Paragraph IV challengers were calculated using data from Abbreviated New Drug Approval (ANDA) letters, the FDA website, public information searches, and ParagraphFour.com. RESULTS: For drugs experiencing initial generic entry in 2013-2014, the MEP was 12.5 years for drugs with sales greater than $250 million (in 2008 dollars) in the year prior to generic entry ($250 million + NMEs), 13.6 years overall. After generic entry, brands rapidly lost sales, with their average unit share being 7% at 1 year for $250 million + NMEs, 12% overall. Ninety-four percent of $250 million + NMEs experiencing initial generic entry in 2013-2014 had faced at least one Paragraph IV challenge, an average of 5.2 years after brand launch (76% and 5.9 years for all NMEs). NMEs faced an average of 5.1 and 6.2 Paragraph IV challenges per NME, for all and $250 million + NMEs, respectively. LIMITATIONS: Analyses, including Paragraph IV calculations, were restricted to NMEs where generic entry had occurred. CONCLUSION: The average 2013-2014 MEP of 12.5 years for $250 million + NMEs, 13.6 overall remains consistent with prior research. MEPs are lower, and Paragraph IV challenges are more frequent and occur earlier for $250 million + drugs. Generic share erosion is also greater, and continues to intensify for both NME types.

Iron Age and Anglo-Saxon genomes from East England reveal British migration history.

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain.

Evolving provider payment models and patient access to innovative medical technology.

UNLABELLED: Abstract Objective: To investigate the evolving use and expected impact of pay-for-performance (P4P) and risk-based provider reimbursement on patient access to innovative medical technology. METHODS: Structured interviews with leading private payers representing over 110 million commercially-insured lives exploring current and planned use of P4P provider payment models, evidence requirements for technology assessment and new technology coverage, and the evolving relationship between the two topics. RESULTS: Respondents reported rapid increases in the use of P4P and risk-sharing programs, with roughly half of commercial lives affected 3 years ago, just under two-thirds today, and an expected three-quarters in 3 years. All reported well-established systems for evaluating new technology coverage. Five of nine reported becoming more selective in the past 3 years in approving new technologies; four anticipated that in the next 3 years there will be a higher evidence requirement for new technology access. Similarly, four expected it will become more difficult for clinically appropriate but costly technologies to gain coverage. All reported planning to rely more on these types of provider payment incentives to control costs, but didn't see them as a substitute for payer technology reviews and coverage limitations; they each have a role to play. LIMITATIONS: Interviews limited to nine leading payers with models in place; self-reported data. CONCLUSION: Likely implications include a more uncertain payment environment for providers, and indirectly for innovative medical technology and future investment, greater reliance on quality and financial metrics, and increased evidence requirements for favorable coverage and utilization decisions. Increasing provider financial risk may challenge the traditional technology adoption paradigm, where payers assumed a 'gatekeeping' role and providers a countervailing patient advocacy role with regard to access to new technology. Increased provider financial risk may result in an additional hurdle to the adoption of new technology, rather than substitution of provider- for payer-based gatekeeping.

Recent trends in brand-name and generic drug competition.

OBJECTIVE: To provide evidence on recent trends in: (1) market exclusivity periods (MEPs, the time between launch of a brand-name drug and its first generic competitor) for new molecular entities (NMEs); (2) the likelihood and timing of patent challenges under Paragraph IV of the Hatch-Waxman Act; and (3) generic drug penetration. METHODS: IMS Health National Sales Perspectives data were used to calculate MEPs for the 257 NMEs experiencing initial generic entry between January 1995 and September 2012 and the number of generic competitors for 12 months afterwards, by level of annual sales prior to generic entry and time period. The likelihood and timing of Paragraph IV challenge were calculated using data from Abbreviated New Drug Approval (ANDA) approval letters, the FDA website, and public information searches to identify drugs experiencing Paragraph IV filings, and the first filing date. RESULTS: For drugs experiencing initial generic entry in 2011-2012, the MEP was 12.6 years for drugs with sales greater than $100 million (in 2008 dollars) in the year prior to generic entry, 12.9 years overall. After generic entry, the brand rapidly lost sales, with average brand unit share of 16% at 1 year; 11% for NMEs with pre-generic entry sales of at least $250 million (in 2008 dollars). Over 80% of NMEs experiencing 2011-2012 initial generic entry had faced at least one Paragraph IV challenge from a generic manufacturer. These challenges were filed relatively early in the brand-name drug life cycle: within 7 years after brand launch, on average. LIMITATIONS: Analyses, including Paragraph IV calculations, were restricted to NMEs where generic entry had occurred. CONCLUSION: Pharmaceutical competition continues to evolve; while the average MEP below 13 years for 2011-2012 remains consistent with prior research, Paragraph IV challenges are increasingly frequent and occur earlier, and generic share erosion has intensified.

Evolving brand-name and generic drug competition may warrant a revision of the Hatch-Waxman Act.

The evolution of pharmaceutical competition since Congress passed the Hatch-Waxman Act in 1984 raises questions about whether the act's intended balance of incentives for cost savings and continued innovation has been achieved. Generic drug usage and challenges to brand-name drugs' patents have increased markedly, resulting in greatly increased cost savings but also potentially reduced incentives for innovators. Congress should review whether Hatch-Waxman is achieving its intended purpose of balancing incentives for generics and innovation. It also should consider whether the law should be amended so that some of its provisions are brought more in line with recently enacted legislation governing approval of so-called biosimilars, or the corollary for biologics of generic competition for small-molecule drugs.

Authorized generic drugs, price competition, and consumers' welfare.

The growing frequency of authorized generics has important implications for the welfare of prescription drug consumers. Authorized generic entry could affect the timing of generic entry, brand-name and generic prices, and generic penetration. We reviewed 1999-2003 data and found that generic entry in the absence of short-run exclusivity restrictions benefits consumers through lower short-run prices. We suggest that these benefits likely also result from authorized generics. We posit that long-run prices and shares are likely essentially unaffected by authorized generics and that potential costs to consumers from any delayed generic entry are likely small.

Up, up and away. Malpractice insurance costs continue to soar.

An overview of the malpractice insurance market in the United States today: which insurers remain, what clients they're willing to cover, and what may lie ahead for the troubled industry.