Entry Of New Drugs Research Articles

Spending on and Use of Clinician-Administered Drugs in Medicare

Medicare Part B drug expenditures have increased in recent years. This trend is likely to persist given the increased use and availability of biologics. To assess the extent to which Medicare Part B spending growth was associated with changes in price vs quantity, and how these trends interacted with entry of new drugs into the marketplace. This cross-sectional study quantified the degree of spending concentration and the association between price and use of Part B drugs among fee-for-service Medicare beneficiaries. Data on use and spending for separately payable Part B drugs were included. Source data were aggregated to the drug-year level and reported from 2016 to 2020. Descriptive decomposition and index analyses quantified the relative association of price and use changes separately for existing single-source drugs, existing drugs that faced competition, and new drugs that entered the market. Data analysis was performed from June to December 2022. Part B drug spending by the fee-for-service Medicare program and beneficiaries, as well as use, defined as dosage units and beneficiaries using the drugs. The study included 535 unique Part B drug products. From 2016 to 2020, 15 or fewer products comprised half of all Part B drug expenditures. The set of 7 drugs that comprised the top 25% of spending was very consistent over time, and all were biologics. Part B drug products that cost $1.85 or less per administration accounted for more than half of the doses administered in 2020. Spending on Part B drugs increased by $15 billion from 2016 to 2020. The entry of new, nonbiosimilar drugs during this period accounted for $12 billion of this increased spending (80%), while shifts in use and price increases among existing single-source brand drugs accounted for the remaining increase in spending. Part B spending decreased among the subset of existing drugs facing generic or biosimilar competition. Among single-source drugs on the market in 2016, the index that varied dosage units exceeded the index that varied price in all years, confirming that changes in use were associated more with spending growth for those drugs. In this cross-sectional study of Medicare Part B drug expenditures, spending was found to be concentrated among a small number of drugs. The entry of new products was a key factor associated with recent increases in Part B drug spending. These findings suggest that policies targeting top-selling drugs may have greater potential to curb Part B drug spending than those targeting price growth.

EE281 Trends in Approvals and Price at Market Entry of New Drugs for Breast Cancer in the US (1980-2022)

To assess trends in approvals and cost of treatment at the market entry of new breast cancer drugs and therapeutic biologics approved by the FDA during 1980-2022.

The effect of pharmaceutical innovation on longevity: Evidence from the U.S. and 26 high-income countries

This study examines the impact that pharmaceutical innovation, which accounts for most private biomedical research expenditure, has had on longevity. We perform two types of two-way fixed-effects analyses, which control for the effects of many potentially confounding variables. First, we analyze long-run (2006–2018) changes in longevity associated with different diseases in a single country: the U.S. Then, we analyze relative longevity levels associated with different diseases in 26 high-income countries during a single time period (2006–2016). The measure of longevity we analyze, mean age at time of death, is strongly positively correlated across countries with life expectancy at birth. The measure of pharmaceutical innovation we use is the mean vintage (year of initial world launch) of the drugs used to treat each disease in each country. Changes in the vintage distribution of drugs are due to both entry of new drugs and exit of old drugs. Our analysis of U.S. data indicates that the diseases for which there were larger increases in drug vintage tended to have larger increases in the longevity of Americans of all races and both sexes. In other words, the lower the mean age of the drugs, the higher the mean age at death. We test, and are unable to reject, the “parallel trends” hypothesis. We estimate that the 2006–2018 increase in drug vintage increased the mean age at death of Americans by about 6 months (66% of the observed increase). Controlling for sex, race, and education has only a small effect on the estimate of the vintage coefficient. The estimates indicate that drug vintage did not have a significant effect on the mean age at death of decedents with less than 9 years of education. Drug vintage had a positive and significant effect on the mean age at death of decedents with at least 9 years of education, and a larger effect on the mean age at death of decedents with at least 13 years of education. The finding that pharmaceutical innovation has a larger effect on the longevity of people with more education is consistent with previous evidence that more educated people are more likely to use newer drugs. Our analysis of data on 26 high-income countries indicates that the higher the vintage of drugs available to treat a disease in a country, the higher mean age at death was, controlling for fixed disease and country effects. The increase in drug vintage is estimated to have increased mean age at death in the 26 countries by 1.23 years between 2006 and 2016—73% of the observed increase. We obtain estimates of the cost of pharmaceutical innovation—its impact on drug expenditure—as well as estimates of an important benefit of pharmaceutical innovation—the number of life-years gained from it—and of their ratio, i.e., the incremental cost-effectiveness ratio. Estimates of the cost per life-year gained for the U.S. and the 26 countries are $35,817 and $13,904, respectively. Both figures are well below per capita GDP in the respective regions, suggesting that, overall, pharmaceutical innovation was highly cost-effective.

Are drug prices subject to creative destruction? Evidence from the US, 1997-2017.

There are several types of pharmaceutical competition. In addition to competition among producers of the same chemical substance ("within-substance competition"), there may be competition among producers of different chemical substances in the same chemical subgroup ("between-substance competition"). There have been numerous econometric studies of the effect of within-substance competition on drug prices, but empirical evidence about the effect of between-substance competition is far more limited. The primary objective of this study is to assess the impact of the entry of new drugs in a drug's therapeutic class on branded drug prices, generic drug prices, and the generic market share, using publicly-available US data for the period 1997-2017. Two methods are used to estimate the effects of between-substance and within-substance competition on those variables. The first method is standard 2-way fixed effects estimation based on aggregate data. The second method, based on micro data, is estimation using the DID_MULTIPLEGT procedure developed by de Chaisemartin etal.(2021), which does not rely on, and allows us to test for, "parallel trends." Between-substance competition does not appear to have any effect on brand-name drug prices, although our inability to fully account for rebates may bias the estimates towards zero. (There is also little evidence for an effect of within-substance competition on brand-name drug prices.) However, between-substance competition has a significant negative effect on generic drug prices. We estimate that the 1985-2005 increase in the number of substances ever registered in a drug's ATC4 chemical subgroup reduced the 2017 price of generic drugs by 42%. (The ratio of the generic-price reduction attributable to rising between-substance competition to the generic-price reduction attributable to rising within-substance competition also happens to be 42%.) A striking finding is that the entry of imitators has no effect on the prices of brand-name drugs, but the entry of innovators has a significant negative effect on the prices of generic drugs in the same ATC4 chemical subgroup. In addition, between-substance competition has a significant positive effect on the generic market share: the 1985-2005 increase in the number of substances ever registered in a drug's ATC4 chemical subgroup increased the 2017 generic market share by 15.0 percentage points. Due to its effects on generic drug prices and the generic market share, the 1985-2005 increase in between-substance competition reduced the average 2017 price of drugs that were already sold in 1997 by 35%. We estimate that 36% of 2017 expenditure on drugs that were first registered during 1986-2005 was offset by reduced 2017 expenditure on drugs that were sold in both 1997 and 2017.

Anesthetic and Analgesic Drug Products Advisory Committee Activity and Decisions in the Opioid-crisis Era.

The United States Food and Drug Administration is tasked with ensuring the efficacy and safety of medications marketed in the United States. One of their primary responsibilities is to approve the entry of new drugs into the marketplace, based on the drug's perceived benefit-risk relationship. The Anesthetic and Analgesic Drug Product Advisory Committee is composed of experts in anesthesiology, pain management, and biostatistics, as well as consumer and industry representatives, who meet several times annually to review new anesthetic-related drugs, those seeking new indications, and nearly every opioid-related application for approval. The following report describes noteworthy activities of this committee since 2017, as it has grappled, along with the Food and Drug Administration, to balance the benefit-risk relationships for individual patients along with the overarching public health implications of bringing additional opioids to market. All anesthesia advisory committee meetings since 2017 will be described, and six will be highlighted, each with representative considerations for potential new opioid formulations or local anesthetics.

PHP30 - THE CONTRIBUTION OF NEW PRODUCT ENTRY VS EXISTING PRODUCT INFLATION IN THE RISING COSTS OF PRESCRIPTION DRUGS IN THE UNITED STATES

To quantify the contribution of existing drug inflation versus the market entry of new drug products in the rising costs of prescription drugs in the United States. We obtained monthly wholesale acquisition costs (WACs) for all national drug codes (NDCs) available in 2005-2016 for oral (n=24,877) and injectable drugs (n= 3,049) and annual counts of pharmacy claims from UPMC Health Plan. We categorized NDC codes into new and existing products; oral and injectable drugs; and brand-name, specialty, and generic drugs. Each year, new drug products were defined as those becoming available within the last 3 calendar years, existing drugs were those available before then. We calculated the average costs of drugs each year, weighting each NDC by counts of pharmacy claims. We calculated annual changes in average weighted costs of all drugs available every year and quantified the contribution of existing versus new drug products in such changes. Increases in average weighted costs exceeded general inflation across all drug classes. Average weighted costs of oral brand-name drugs increased annually by 6.8% on average, with 72.4% of this increase being attributed to existing drugs, and 27.6% to new drugs. Average weighted costs of injectable brand-name drugs increased annually by 14.8% on average, also driven by existing drug inflation. For oral and injectable specialty drugs, average weighted costs increased annually 27.4% and 13.1%, respectively, largely attributed to entry of new drugs (88.8% and 74.5%, respectively). Average weighted costs of oral and injectable generics increased by 3.9% and 7.3%, respectively, and were also driven by the entry of new drug products. Drug costs increased considerably faster than inflation across all classes. Rising costs of generic and specialty drugs were driven by the entry of new drug products, whereas rising costs of brand-name drugs were due to existing drug inflation

Information on new drugs at market entry: retrospective analysis of health technology assessment reports versus regulatory reports, journal publications, and registry reports

Background When a new drug becomes available, patients and doctors require information on its benefits and harms. In 2011, Germany introduced the early benefit assessment of new drugs through the...

Provincial Entry of New Drugs In China.

To improve health care provision whilst containing cost at the same time, Chinese authorities allow the entry of new drugs at provincial level. Whilst different provinces have different economic situation and needs, it is essential for pharmaceutical companies to strategize provincial drug entry. The purpose of this research is to explore province (s) that may provide the best chance for new drug entry. To capture all the drugs that were newly included in the 2012 National Drug List (NDL) but not the 2009 NDL, multiple databases including the two NDLs, Adis Insight and the Chinese database Yao-zhi Shu-ju were used. Provincial reimbursement status of these drugs was identified using the Chinese database. Provincial population and economic data (including gross domestic product (GDP), health expenditure and consumer price index (CPI) ) in 2011 were captured on the National Statistical Database. The correlation between the numbers of provincially reimbursed drugs (with/without restrictions) and GDP per capita, and between the numbers of provincially reimbursed drugs (with/ without restrictions) and regional health expenditure, were investigated. All databases were accessed in September 2013. 245 new formulations were identified, among which 35 of them are alternative formulations of 26 new drugs. Among the 23 provinces and 4 municipalities provinces, Anhui (48%) followed by Jiangsu (20%) approved most new drugs without restrictions. Guangxi (21%) was the autonomous region approved most new drugs without restrictions. Among the provincially reimbursed drugs, Jilin (62%) was the province approved most drugs associated with restrictions. The number of approved drugs was not correlated to regional GDP per capita (p=0.18, r2=0.06) nor with regional health expenditure (p=0.78, r2=0.003). There is a substantial variation in the number of approved new drugs between provinces in China. The economic status of the provinces is not likely to be the sole factor causing such differentiation.

Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs.

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction.Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities.Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies.Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice.Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

PP084—A European score predicts better south american cardiovascular risk than framingham risk equations

e44 Volume 35 Number 8S to optimize the managed entry of new drugs in the future through an iterative process. This includes guidance for all key groups on future activities to achieve this. Results: There have been multiple demand-side activities among countries to manage the utilization of dabigatran. This included extensive prelaunch activities, risk-sharing arrangements, prescribing restrictions, and monitoring of prescribing postlaunch against agreed guidance. Clinical pharmacologists played a key role in a number of countries. Reimbursement was denied in some countries due to concerns with its budget impact and/or issues with excessive bleeding. Development of a new model and future guidance was proposed to better manage the entry of new drugs in the future, centring on 3 pillars of pre-, peri-, and postlaunch activities. This was accompanied by guidance to all key stakeholder groups, including health authorities, physicians, patients, and pharmaceutical companies on suggested activities preto postlaunch to reduce the likelihood of new drugs being withdrawn as well as enhance their chances of funding. This included guidance on key considerations that authorities should consider when evaluating risk-sharing arrangements or developing patient registries. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. As a result, promote high prescribing standards postlaunch. Without such models, new drugs may be withdrawn prematurely and/ or struggle for funding. Financial Source: The project was funded by a grant from the Karolinska Institutet. Most of the co-authors are either employed by health authorities or are advisers to them. Disclosure of Interest: None declared.

PP083—Dabigatran– demonstrates the need for comprehensive approaches to optimise the use of new drugs

There are potential conflicts between authorities and companies to fund new premium-priced drugs, especially where there are safety and/ or budget concerns. Dabigatran exemplifies these issues due to variable drug concentrations, no known antidote, dependence on renal elimination, and considerably more expensive than warfarin. The latter is a concern with the growing prevalence of atrial fibrillation (AF). There are also issues with potentially re-designing anticoagulant services. As a result, there is a need to review authority activities regarding dabigatran and use the findings to develop new models to better manage the entry of new drugs in the future.

Dabigatran – a case history demonstrating the need for comprehensive approaches to optimize the use of new drugs

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies have shown dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. There are also issues with potentially re-designing anticoagulant services. This has resulted in activities across countries to better manage its use.Objective: To (i) review authority activities in over 30 countries and regions, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications for all major stakeholder groups.Methodology: Descriptive review and appraisal of activities regarding dabigatran and the development of guidance for groups through an iterative process.Results: There has been a plethora of activities among authorities to manage the prescribing of dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions, and monitoring of prescribing post-launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities.Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where there are concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

Improving the managed entry of new medicines: sharing experiences across Europe

The Managed Introduction of New MedicinesLjubljana, Slovenia, 19–21 March 2012The 3-day course on the managed entry of new medicines was run by the Piperska group, which is a pan-European group striving to enhance the health of the public as a whole and the individual patient through exchanging ideas and research around the rational use of drugs. Participants included health authority and health insurance personnel, academics and those from commercial organizations. The principal aim of the conference was to bring together people to discuss ways to improve the managed entry of new drugs.

Diffusion of innovations in social interaction systems. An agent-based model for the introduction of new drugs in markets

The existence of imitative behavior among consumers is a well-known phenomenon in the field of Economics. This behavior is especially common in markets determined by a high degree of innovation, asymmetric information and/or price-inelastic demand, features that exist in the pharmaceutical market. This paper presents evidence of the existence of imitative behavior among primary care physicians in Galicia (Spain) when choosing treatments for their patients. From this and other evidence, we propose a dynamic model for determining the entry of new drugs into the market. To do this, we introduce the structure of the organization of primary health care centers and the presence of groups of doctors who are specially interrelated, as well as the existence of commercial pressure on doctors. For modeling purposes, physicians are treated as spins connected in an exponentially distributed complex network of the Watts-Strogatz type. The proposed model provides an explanation for the differences observed in the patterns of the introduction of technological innovations in different regions. The main cause of these differences is the different structure of relationships among consumers, where the existence of small groups that show a higher degree of coordination over the average is particularly influential. The evidence presented, together with the proposed model, might be useful for the design of optimal strategies for the introduction of new drugs, as well as for planning policies to manage pharmaceutical expenditure.

The Impact of Public Basic Research on Industrial Innovation: Evidence from the Pharmaceutical Industry

While most economists believe that public scientific research fuels industry innovation and economic growth, systematic evidence supporting this relationship is surprisingly limited. In a recent study, Acemoglu and Linn (2004) identified market size as a significant driver of drug innovation in the pharmaceutical industry, but they did not find any evidence supporting science-driven innovation from publicly funded research. This paper uses new data on biomedical research investments by the U.S. National Institutes of Health (NIH) to examine the contribution of public research to pharmaceutical innovation. The empirical analysis finds that both market size and NIH funded basic research have economically and statistically significant effects on the entry of new drugs with the contribution of public basic research coming in the earliest stage of pharmaceutical drug discovery. The analysis also finds a positive return to public investment in basic biomedical research.

Mathematical Modeling in Immunotherapy of Cancer: Personalizing Clinical Trials

Despite the massive resources currently invested in medical research and development, the rate of entry of new drugs into the market is decreasing. The present system of clinical trials may put too many hurdles in the way of drug development—particularly those targeting cancer, for which the prevalent format of clinical trials was developed long ago mostly to test small molecules. Although the format has been adapted to some protein therapeutics, it is clearly inadequate for the recent, more complex biological treatments. Hence, for these new approaches to help patients, clinical trials must become more innovative and substantially streamlined. This concern has brought up the idea of information technology–mediated trials (“e-trials”) that could broaden the patient base.1 Another idea is that of virtual research and development, using computer simulations of the human body intended to replace the laborious efficacy testing in real humans and reduce the likelihood of drug failure.2

The impact of public basic research on industrial innovation: Evidence from the pharmaceutical industry

While most economists believe that public scientific research fuels industry innovation and economic growth, systematic evidence supporting this relationship is surprisingly limited. In a recent study, Acemoglu and Linn (2004) identified market size as a significant driver of drug innovation in the pharmaceutical industry, but they did not find any evidence supporting science-driven innovation from publicly funded research. This paper uses new data on biomedical research investments by the U.S. National Institutes of Health (NIH) to examine the contribution of public research to pharmaceutical innovation. The empirical analysis finds that both market size and NIH funded basic research have economically and statistically significant effects on the entry of new drugs with the contribution of public basic research coming in the earliest stage of pharmaceutical drug discovery. The analysis also finds a positive return to public investment in basic biomedical research.

Abstract IA-12: Oncology drug discovery and development in the 21st century

Abstract Oncology drug discovery and development is poised to enter an era of unparalleled growth. Based on an increasingly detailed understanding of human genetics and cancer biology, new targets have emerged that go beyond nucleic acids and microtubules to members of signal transduction pathways that are upstream of these fundamental cellular structures. In addition, an appreciation of the effects of the tumor microenvironment on cancer cell pathophysiology and metabolism has focused increasing attention on targets in these areas. With more than 200 compounds in the Pharmaceutical Industry's pipeline, substantial improvements in the lives of cancer patients are anticipated. Yet major hurdles exist. Despite the increased knowledge and investment in drug development, the entry of new drugs into the clinic has not kept pace. Key barriers include but are not limited to: 1. Understanding the role of a drug target in the context of an individual's malignancy; 2. Predicting characteristics of a patient and his or her cancer that is most likely to benefit from a specific therapy; 3. Predicting the toxicity of new agents; 4. Outmoded clinical trial designs; 5. Developing rational drug combinations; 6. Accrual to clinical trials; 7. Appropriate resourcing of regulatory agencies and; 8. the price of developing cancer drugs. This presentation will address each of these challenges and suggest ways in which progress can be made. Citation Information: Cancer Res 2009;69(23 Suppl):IA-12.

Patent life of antiretroviral drugs approved in the US from 1987 to 2007

This study analyzes the effective patent life of antiretroviral (ARV) new molecular entities (NMEs) approved for marketing in the United States (US) between 1987 and 2007. The study includes all NMEs approved during the study period with at least one patent listed in the Orange Book (OB). Drugs discontinued from the market were excluded from the analysis. Data sources are the US Food and Drug Administration (FDA) and the US Patent and Trademark Office. A comparison between the effective patent life of ARV NMEs and NMEs from other therapeutic classes was performed. The first and last patents were used to estimate the minimum and maximum effective patent life of NMEs. Group differences were assessed using group comparison t-tests, Chi-Square and Fishers’ exact tests. The FDA approved 547 NMEs during the study period; 153 NMEs did not have a patent listed in the OB or were discontinued from the US market. The patent analysis included 22 ARV NMEs and 372 other NMEs. ARV MNEs had a range from 1 to 15 patents listed in the OB. The FDA new drug application (NDA) review time was shorter for ARVs (5.8±2.3 months) than for other NMEs (23.6±18.7 months). ARV NMEs had an average of 13.2±3.8 years of effective patent life for the first patent versus 11.0±4.2 years for other NMEs. ARV NMEs had an average of 17.5±3.6 years of effective patent life for the last patent versus the 14.8±4.8 years for other NMEs. The effective patent life listed for the last patent of seven ARV NMEs (31.8%) exceeded 20 years. Shortening the drug approval process increased the effective patent life of ARVs and facilitated faster entry of new drugs into the market. ARVs had an average of 2–3 more years of effective patent life than other therapeutic classes and, therefore, a longer period without generic competition.

Should we really worry about “launch delays” of new drugs in OECD countries?

In the last few years, the role of pharmaceutical price controls has been frequently questioned by economists on the grounds that they lower investments in research and development (R&D), due to reduced profitability [1]. A recent article by Danzon, Wang and Wang (hereafter, DWW [2]), although related to this general topic, somehow shifts the perspective, focusing on the effects of price regulation on strategic decisions to launch new chemical entities (NCEs) and finding that low prices in a therapeutic class are significantly related to launch delays of NCEs. DWW claim that these de lays might be mainly a consequence of companies' decisions to avoid price spillovers due to parallel trade and external referencing. After DWW, further "launch delay" literature appeared. Lanjow [3] and Kyle [4] reached similar conclusions to DWW, although using different data and techniques. The issue of launch delays becomes even more important in relation to the economic literature. For example, in different analyses Lichtenberg [5, 6] found that, compared to old products, NCEs are better at "keeping people out of the hospital" and improving life expectancy. A generalization of Lichtenberg's re sults would imply that lower prices may negatively affect overall social welfare by creating barriers to the entry of new drugs [7]. We think the question is