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Applied Health Economics and Health... Sep 2022Oncology drugs are often approved for multiple indications, for which their clinical benefit varies. Aligning a single price to this differing value remains a challenge....
PURPOSE
Oncology drugs are often approved for multiple indications, for which their clinical benefit varies. Aligning a single price to this differing value remains a challenge. This study examines the clinical and economic value, price, and reimbursement of multi-indication cancer drugs across seven countries, representing different approaches to value assessment, pricing, and coverage decisions: the USA, Germany, France, England, Canada, Australia, and Scotland.
METHODS
Twenty-five multi-indication cancer drugs across 100 indications were identified with US Food and Drug Administration (FDA) approval between 2009 and 2019. For each indication data on Health Technology Assessment (HTA) recommendations, disease prevalence, and drug prices were obtained. Quality-adjusted life years (QALYs) gained, disease prevalence, list prices, and HTA outcomes were then compared across indications and regions.
RESULTS
First approved indications provide a higher clinical benefit whilst targeting a smaller patient group than indication extensions. Quality-adjusted life year gains were higher for first (0.99, 95% CI 0.05-3.25) compared to second (0.51, 95% CI 0.02-1.63, p < 0.001) and third (0.58, 95% CI 0.05-2.07, p < 0.01) approved indications. Disease prevalence per 100,000 inhabitants was 20.7 (95% CI 0.2-63.3) for first compared to 27.1 (95% CI 1.5-109.6, p = 0.907) for second and 128.3 (95% CI 3.1-720.1, p < 0.001) for third approved indications. With each approved indication drug prices declined in Germany and France, remained constant in the UK, Canada, and Australia, whilst they increased in the USA. Negative HTA outcomes, clinical restrictions, and managed entry agreements (MEAs) were more frequently observed for indication extensions.
CONCLUSIONS
Results suggest that indication development is prioritised according to clinical value and disease prevalence. Countries employ different mechanisms to account for each indication's differential benefit, e.g., weighted-average prices (Germany, France, Australia), differential discounts (England, Scotland), clinical restrictions, and MEAs (England, Scotland, Australia, Canada). Value-based indication-specific pricing can help to align the benefit and price for multi-indication cancer drugs.
Topics: Antineoplastic Agents; Canada; Drug Costs; France; Germany; Humans; Neoplasms; Pharmaceutical Preparations
PubMed: 35821360
DOI: 10.1007/s40258-022-00737-w -
Journal of Market Access & Health Policy 2016Indication value-based pricing (IBP) has been proposed in the United States as a tool to capture the differential value of drugs across indications or patient groups and... (Review)
Review
Indication value-based pricing (IBP) has been proposed in the United States as a tool to capture the differential value of drugs across indications or patient groups and is in the early phases of implementation. In Europe, no major country has experimented with IBP or is seriously discussing its use. We assessed how the reimbursement and pricing environment allows for IBP in seven European countries, evaluating both incentives and hurdles. In price setting countries such as France and Germany, the Health Technology Assessment and pricing process already accounts for differences of value across indications. In countries where differential value drives coverage decisions such as the United Kingdom and Sweden, IBP is likely to be used, at least partially, but not in the short-term. Italy is already achieving some form of differential value through managed entry agreements, whereas in Spain the electronic prescription system provides the infrastructure necessary for IBP but other hurdles exist.
PubMed: 27226845
DOI: 10.3402/jmahp.v4.30970 -
Journal of the American College of... Mar 2021The Protecting Access to Medicare Act of 2014 requires clinicians to consult Appropriate Use Criteria (AUC) when ordering advanced imaging procedures. Free-text order...
OBJECTIVE
The Protecting Access to Medicare Act of 2014 requires clinicians to consult Appropriate Use Criteria (AUC) when ordering advanced imaging procedures. Free-text order indications are available when there is no applicable structured indication but are unscored by the AUC. We determined the proportion of free-text indications among all advanced imaging orders and the proportion of free-text indications that could be mapped to a single structured indication.
METHODS
All outpatient advanced diagnostic imaging orders placed in a large multisite health system were recorded after initial AUC deployment (November 20, 2017, to December 19, 2017). Clinicians were prompted upon order entry to select a structured indication or enter a free-text indication. We manually reviewed the two imaging examinations with the highest rate of free-text indications: enhanced CT abdomen/pelvis and unenhanced CT head. Regression analysis examined differences in patient-, imaging-, context-, and provider-level characteristics between scored and unscored examinations.
RESULTS
Among all 39,533 orders for advanced imaging procedures, 59% (23,267 of 39,533) were unscored by the system. The regression model c-statistic (0.50-0.55) demonstrated poor model fit to evaluate for differences between scored and unscored examinations. Free-text indications were found in 71% (16,440 of 23,267) of unscored examinations and 42% (16,440 of 39,533) of all examinations. Manual review of all 1,693 CT abdomen/pelvis and 1,527 CT head examinations with free-text indications revealed that 3,132 free-text indications (97%) could be mapped to a single existing structured indication.
DISCUSSION
Of all initially placed outpatient advanced imaging procedure orders, 42% included free-text indications and 97% of manually reviewed free-text indications could be mapped to a single structured indication.
Topics: Aged; Decision Support Systems, Clinical; Epidemics; Humans; Medical Order Entry Systems; Medicare; Tomography, X-Ray Computed; United States
PubMed: 33663756
DOI: 10.1016/j.jacr.2021.01.002 -
Therapeutic Innovation & Regulatory... Mar 2022This study evaluates the association of Biopharma company valuation with the lead drug's development stage, orphan status, number of indications, and disease area. We...
OBJECTIVES
This study evaluates the association of Biopharma company valuation with the lead drug's development stage, orphan status, number of indications, and disease area. We also estimated annual returns Bioentrepreneurs and investors can expect from founding and investing in drug development ventures.
METHODS
SDC Thomson Reuter and S&P Capital IQ were screened for majority acquisitions of US and EU Biopharma companies developing new molecular entities for prescription use (SIC code: 2834). Acquisition data were complemented with drug characteristics extracted from clinicaltrials.gov, the US Food and Drug Administration (FDA), and deal announcements. Thereafter, company valuations were combined with previously published clinical development periods alongside orphan-, indication-, and disease-specific success rates to estimate annual returns for investments in drug developing companies.
RESULTS
Based on a sample of 311 Biopharma acquisitions from 2005 to 2020, companies developing orphan, multi-indication, and oncology drugs were valued significantly higher than their peers during later development stages (p < 0.05). We also estimated significantly higher returns for shareholders of companies with orphan relative to non-orphan-designated lead drugs from Phase 1 to FDA approval (46% vs. 12%, p < 0.001). Drugs developed across multiple indications also provided higher returns than single-indication agents from Pre-Clinic to FDA approval (21% vs. 11%, p < 0.001). Returns for oncology drugs exceeded other disease areas (26% vs. 8%, p < 0.001).
CONCLUSIONS
Clinical and economic conditions surrounding orphan-designated drugs translate to a favorable financial risk-return profile for Bioentrepreneurs and investors. Bioentrepreneurs must be aware of the upside real option value their multi-indication drug could offer when negotiating acquisition or licensing agreements.
Topics: Drug Development; Negotiating; Orphan Drug Production; United States; United States Food and Drug Administration
PubMed: 35018622
DOI: 10.1007/s43441-021-00364-y -
PloS One 2021The aim of this scoping review was to determine the extent of off-patent prescription medicine use beyond registered indications in various Australian clinical settings. (Review)
Review
AIM
The aim of this scoping review was to determine the extent of off-patent prescription medicine use beyond registered indications in various Australian clinical settings.
METHOD
The review followed the Joanna Briggs Institute approach and reported using PRISMA Extension for Scoping Reviews. Online databases were used to identify published literature about off-patent registered prescription medicines used for off-label indications in Australian public hospital, community and primary healthcare settings. In addition, empirical data from the Queensland and the South Australian state-wide medicine formularies were screened for the same medication/off-label indication dyads identified in the literature, and other locally approved uses.
RESULTS
Overall, fourteen studies were included, conducted in public hospitals (n = 11), palliative care units (n = 2) and the community setting (n = 1). There were 213 reports extracted from the literature describing off-patent registered prescription medicines used for off-label indications, representing 128 unique medication/off-label indication dyads and 32 different medicines. Of these, just five medication/off-label indication dyads were approved for use on both the Queensland and South Australian state-wide medicine formularies, with 12 others only approved for use in Queensland and 16 others only approved for use in South Australia. Further examination of these state-wide formularies demonstrated that the use of off-patent registered prescription medicines beyond registered indications is more extensive than has been reported to date in the literature. There were 28 additional medication/off-label indication dyads approved on the Queensland state-wide medicine formulary and 14 such examples approved for use in South Australia. Of these, just two medication/off-label indication dyads were approved for use on both formularies.
CONCLUSION
The extent to which off-patent registered prescription medicines have been repurposed in clinical settings for off-label indications in Australia is greater than previously reported in the literature. Usage and funded availability of certain medication/off-label indication dyads, varies across Australia. These results further expose the two tiered system of medicines regulation in Australia, and its impact on equity of access to medicines. Further research is required to support policy change to encourage submission of registration updates for off-patent prescription medicines.
Topics: Australia; Humans; Off-Label Use; Patents as Topic; Prescription Drugs
PubMed: 34860857
DOI: 10.1371/journal.pone.0261022 -
Biologics : Targets & Therapy 2017Extrapolation is the approval of a biosimilar for use in an indication held by the originator biologic not directly studied in a comparative clinical trial with the... (Review)
Review
Extrapolation is the approval of a biosimilar for use in an indication held by the originator biologic not directly studied in a comparative clinical trial with the biosimilar. Extrapolation is a scientific rationale that bridges all the data collected (ie, totality of the evidence) from one indication for the biosimilar product to all the indications originally approved for the originator. Regulatory approval and marketing authorization of biosimilars in inflammatory indications are made on a case-by-case and agency-by-agency basis after evaluating the totality of evidence from the entire development program. This totality of the evidence comprises extensive comparative analytical, functional, nonclinical, and clinical pharmacokinetic/pharmacodynamic, efficacy, safety, and immunogenicity studies used by regulators when evaluating whether a product can be considered a biosimilar. Extrapolation reduces or eliminates the need for duplicative clinical studies of the biosimilar but must be justified scientifically with appropriate data. Understanding the concept, application, and regulatory decisions based on the extrapolation of data is important since biosimilars have the potential to significantly impact patient care in inflammatory diseases.
PubMed: 28255229
DOI: 10.2147/BTT.S124476 -
BMC Pediatrics Jan 2021Upper endoscopy is an essential tool for diagnosing pediatric gastrointestinal issues. This study aimed to assess the indications, diagnostic yields, concordance between...
BACKGROUND
Upper endoscopy is an essential tool for diagnosing pediatric gastrointestinal issues. This study aimed to assess the indications, diagnostic yields, concordance between histopathological and endoscopic findings and suitability of upper endoscopies performed at a tertiary university hospital in Jordan.
METHODS
Hospital records of children who underwent upper endoscopy were retrospectively reviewed. Demographics, endoscopic details (e.g., indications, findings and any complications), and histopathological findings were collected. The relationship between endoscopic findings and histopathological abnormalities was reported.
RESULTS
The study included 778 patients (age, 92.5 ± 54.5 months; 380 girls, 48.8%). The most common age group was children younger than 60 months (273 patients, 34.3%). The most common indication for endoscopy was abdominal pain, followed by vomiting and failure to thrive or weight loss. Normal upper endoscopy was reported in 411 patients (52.8%). Age below 60 months, abdominal pain, dysphagia/odynophagia, and heartburn were predictive of abnormal endoscopy in multivariate analysis with p-value 0.000, 0.048, 0.001 and 0.01 respectively. Abnormal endoscopy showed 67.3% sensitivity and 69.9% specificity to predict histopathological abnormalities. Of those performed, 13.6% endoscopies were described as inappropriate indication. The suitability of the procedure was a sensitive predictor for abnormal endoscopic and histopathological findings.
CONCLUSIONS
Abdominal pain is the most common indication for upper endoscopy in our population. It is associated with a higher chance of abnormal endoscopy. Concordance between endoscopic and histopathological findings is not high. Normal endoscopic findings shouldn`t discourage the endoscopist from obtaining tissue biopsies. Considering more biopsies may improve pathological detection rates. Compliance with established endoscopy guidelines may reduce unnecessary procedures.
Topics: Abdominal Pain; Child; Child, Preschool; Deglutition Disorders; Female; Gastrointestinal Diseases; Gastroscopy; Humans; Jordan; Retrospective Studies
PubMed: 33402143
DOI: 10.1186/s12887-020-02470-6 -
Journal of Clinical Medicine Research Sep 2019To understand possible medication overprescribing, it would be important to know which classes are the most prescribed, for which indications, for what duration, and for... (Review)
Review
To understand possible medication overprescribing, it would be important to know which classes are the most prescribed, for which indications, for what duration, and for which age groups. Among the 10 most frequently prescribed medication classes for US adults, four were evaluated for overprescribing, and systematically assessed in relation to their primary indication. The assessment included usage patterns, trends, age of recipients, treatment duration, and benefits versus adverse consequences. The findings in this selective review are supported by an extensive search of the medical literature. The four selected medication categories and their most common indication included opioids for chronic pain, proton pump inhibitors for indigestion, levothyroxine for subclinical hypothyroidism, and antidepressants for subsyndromal levels of depression. These medications, grouped by their most frequent indication along with polypharmacy, have experienced major prescription increases in recent years, particularly among older patients. Most concerning is that they have been frequently prescribed for extended periods, usually with inadequate evidence of benefit. High drug usage patterns can aid in quantifying overprescribing within polypharmacy by age group.
PubMed: 31523334
DOI: 10.14740/jocmr3906 -
California Medicine Feb 1960A synthetic oxytocin, Syntocinon(R), was used in 3,342 obstetrical patients for a wide variety of indications. It was concluded that the preparation is as effective as...
A synthetic oxytocin, Syntocinon(R), was used in 3,342 obstetrical patients for a wide variety of indications. It was concluded that the preparation is as effective as natural oxytocin.(1) There were no side effects observed, particularly vasospasm or anaphylactic reaction. Its use in clinical obstetrics can be recommended provided there is a proper indication for its use and the need for close supervision and individual adjustment of dosage is recognized.
Topics: Oxytocin
PubMed: 14401672
DOI: No ID Found -
Open Forum Infectious Diseases Oct 2022Individuals with hepatitis C (HCV) represent a population that may benefit from pre-exposure prophylaxis (PrEP), given the overlapping risk factors and transmission...
BACKGROUND
Individuals with hepatitis C (HCV) represent a population that may benefit from pre-exposure prophylaxis (PrEP), given the overlapping risk factors and transmission networks of HCV and HIV. This analysis assesses the prevalence of PrEP indications among individuals with HCV monoinfection and PrEP awareness, interest, and access in this population.
METHODS
GRAVITY was an observational study for the collection of epidemiologic data from individuals with HCV and/or HIV in Washington DC and Baltimore, with the present analysis limited to HCV-monoinfected patients. The prevalence of PrEP indications was determined using epidemiologic survey responses. Bivariate and multivariable analyses assessed for associations between PrEP indications and PrEP awareness, access, and interest.
RESULTS
Among 314 HCV-monoinfected participants, 109 (35%) had an indication for PrEP. Forty-eight (44%) had a drug use indication alone, 40 (37%) had a sexual indication alone, and 21 (19%) had both drug use and sexual indications. Eighty-five (27%) participants had heard of PrEP, 32 (10%) had been offered PrEP by a provider, 114 (38%) were interested or maybe interested in PrEP, and 6 (2%) were currently taking PrEP. On bivariate analysis, PrEP awareness was significantly associated with study site ( < .0001), race ( = .0003), age ( < .0001), and sexual PrEP indication ( = .04). However, only study site remained significant ( = .0002) on regression analysis.
CONCLUSIONS
Though indications for PrEP were prevalent among individuals with HCV in this cohort, most patients were unaware of PrEP, had never been offered PrEP, and were not using PrEP. These data support the need for improved PrEP implementation among people with HCV.
PubMed: 36225745
DOI: 10.1093/ofid/ofac476