scholarly journals Ethical and human subject burdens of trials conducted to evaluate biosimilars

2021 ◽  
Author(s):  
Jennifer A. Ohn ◽  
Preston J. Atteberry ◽  
Mark R. Trusheim ◽  
Peter B. Bach
Keyword(s):  
Price Competition ◽  
Human Subject ◽  
Generic Drugs ◽  
Human Subjects ◽  
Drug Approval ◽  
Current Approach ◽  
Cancer Center ◽  
Biologic Drugs ◽  
The Us ◽  
Clinical Benefits

ABSTRACTBackground/AimsWith a policy goal of introducing price competition into the market for biologic drugs after their period of market monopoly is over (called ‘loss of exclusivity’), policymakers created a pathway for companies to make copies of those treatments and termed them ‘biosimilars’. But unlike generic drugs, biosimilar drug copies must be studied in human trials to assure they have the same clinical effect as the original biologic products. The burden that this places on human subject participants, and the opportunity cost on the clinical trial system generally, have not been considered in detail.MethodsFor all biosimilar drugs in development, approved, or that failed to obtain approval in the US, we abstracted from clinicaltrials.gov registry the number of subjects enrolled at each phase of development.ResultsWe identified 105 clinical trials for approved or withdrawn biosimilars and another 20 studies that are either planned, ongoing or completed for biosimilars in development. These studies collectively enrolled (or plan to enroll) 38,169 human subjects. Most (28,130) are enrolled in phase 3 studies. The mean number of human subject participants per approval is 1,045, about 25% of the number required for a new drug approval on average.ConclusionsA consequential number of human subjects are required for the testing of biosimilar drugs prior to approval. The explicit and sole purpose of biosimilars is to induce competition in order to lower prices of biologic drugs after loss of exclusivity. The burden the biosimilar approval trials place on human subjects with no direct clinical benefits but definite risks, and the possibility that they rob subjects from trials that are of more scientific importance, are ones policymakers might consider. Price regulation of biologic drugs after loss of exclusivity could achieve lower prices as well, without the burdens of the current approach.Funding SourceArnold Ventures (Grant to support Drug Pricing Lab at Memorial Sloan Kettering Cancer Center)

Recent developments in US law: Remedies and damages for improper patent listings in the FDA's Orange Book

10.5912/jcb29 ◽  
1969 ◽  
Vol 9 (3) ◽  
Author(s):  
Daniel G Brown
Keyword(s):  
Price Competition ◽  
Generic Drugs ◽  
Pharmaceutical Product ◽  
Pharmaceutical Companies ◽  
White House ◽  
Drug Products ◽  
The Us ◽  
Recent Developments ◽  
The Usa ◽  
Orange Book

The Drug Price Competition and Patent Term Restoration Act (Publ. No. 98-417, 98 Stat. 1585 (1984)), commonly known as the Hatch–Waxman Act (the Act) provides the statutory framework by which most generic drugs are approved for marketing in the USA. Most provisions in the Act concern the standards and procedures the US Food and Drug Administration (FDA) must follow to approve generic drugs. A relatively small number of the provisions, however, create a framework for resolving patent disputes between the brand and generic pharmaceutical companies. These provisions have been the subject of much recent activity, in the US Courts, in Congress, in the FDA itself and in the White House. Much of the activity revolves around a publication by FDA entitled Approved Drug Products with Therapeutic Equivalence Evaluations, known colloquially as the Orange Book.Under present FDA practice, the mere listing of a patent in the Orange Book corresponding to a brand pharmaceutical product invokes a number of statutory provisions that confer valuable exclusivity rights on the brand company, and also possibly on one or more generic companies. This situation creates a strong incentive for patentees and brand pharmaceutical companies to list patents in the Orange Book. A number of recent court cases have addressed the remedies and damages available when the listing is found to be improper. Thus far, the most successful means to challenge or prevent improper listings has been through private and governmental enforcement of the antitrust laws.

scholarly journals Regulatory Prototype for Biological Products in the United States

2021 ◽  
pp. 60-72
Author(s):  
G. M. Pavithra ◽  
N. Venugopal
Keyword(s):  
Price Competition ◽  
Generic Drugs ◽  
The United States ◽  
Biological Application ◽  
Biological Products ◽  
License Application ◽  
The Us ◽  
High Degree ◽  
Degree Of Similarity ◽  
Improve Access

Biological products are used for the treatment of many disease, so the biological application submitted for the approval of products are also increasing. The progress of a biosimilarproduct is more difficult and expensive than a small molecule generic product. Biosimilars are not true generic drugs, but demonstrate a high degree of similarity to the reference biological product. In order to improve access to costly biological treatments, a biosimilar pathway in the US was established under the Biologics Price Competition and Innovation Act of 2009. The study highlighted the “Regulatory prospective for the registration of Biological products in US” and a brief description about the development, Manufacturing and approval process of biosimilar products. This article is also focused on the regulatory framework, Biological License Application, Purple book, and Pharmacovigilance of biological products.

scholarly journals High prices for generics in Australia — more competition might help

2009 ◽  
Vol 33 (2) ◽  
pp. 200 ◽  
Author(s):  
Liliana Bulfone
Keyword(s):  
Price Competition ◽  
Generic Drugs ◽  
Developed Countries ◽  
Dominant Strategy ◽  
Generic Product ◽  
The Us ◽  
Generic Products ◽  
The Government ◽  
The Individual ◽  
Pharmaceutical Benefits Scheme

It is commonly believed that dispensed prices of medicines in Australia are substantially lower than those in other developed countries, particularly the US. This article reports the results of an analysis comparing dispensed prices for the most commonly prescribed and the highest cost items in Australia with dispensed prices in the US. Although a large majority of items are less expensive in Australia than in the US, Australian prices are higher for a substantial number of products, particularly generic drugs. This article examines various policies affecting the pricing of generics in Australia. It is postulated that the main cause for higher prices for a substantial number of generic products is the lack of price competition. This results from government policy which ensures that a price reduction by one company is communicated immediately to all competitors in that market along with an invitation to match the reduced price. The dominant strategy for all suppliers is to only reduce their price in response to a reduction in price by a competitor. The result is a lack of differentiation in pricing across brands of a medicine on the Schedule of Pharmaceutical Benefits. The government could improve the structure of the generics market and encourage greater competition by ceasing to disclose competitor firms? offers to other competitors. The government could conduct pricing reviews of each generic product relatively infrequently (eg, only once annually or every 18 months). At the time of the pricing review, the government would request confidential offers on price for a generic from all players in the market. Brands should then all be listed under the Pharmaceutical Benefits Scheme (PBS) at the offered price. Prices offered by the individual supplier would apply until the next pricing review. The PBS would continue to subsidise up to the price of the lowest priced brand, with brand premiums applying to all brands priced higher than the benchmark price. Such an approach would provide opportunity for players in the market to capture market share by being the lowest priced brand.

Regulatory requirements and comparison in approval of new and generic drugs in United States of America and Japan:-Implication for Future strategies

2020 ◽  
Vol 07 ◽  
Author(s):  
Paramjeet Malik ◽  
Neelam Pawar ◽  
Kavita Bahmani
Keyword(s):  
Generic Drugs ◽  
Drug Product ◽  
Drug Approval ◽  
Approval Process ◽  
Regulatory Requirements ◽  
Team Members ◽  
Regulatory Authorities ◽  
Effective Manner ◽  
Review Team

: Safety, efficacy and quality of a therapeutic product is the major concern for the pharmaceutical companies. FDA and PMDA are the main regulatory authorities in USA & JAPAN respectively that ensures the maintenance of these required parameters by forming standard guidelines and process for drug approval. These regulatory authorities’ reviews each step of a pharmaceutical drug product from its discovery phase to marketed product. Dossier plays an important role during the approval process of a drug product, as it allows both applicant and review team members to evaluate the data in an effective manner. A dossier consists of five modules containing informative data of various stages of a drug product but in a brief pattern with folders and subfolders. In the present paper, the authors focus on in-depth review of approval process for new and generic drugs in USA and Japan.

Role of Topical Oxymetazoline for Management of Erythematotelangiectatic Rosacea

2017 ◽  
Vol 52 (3) ◽  
pp. 263-267 ◽  
Author(s):  
Rebecca M. Hoover ◽  
John Erramouspe
Keyword(s):  
English Language ◽  
Human Subjects ◽  
Data Extraction ◽  
Drug Approval ◽  
Current Data ◽  
Patient Response ◽  
Study Selection ◽  
Cochrane Database ◽  
Drug Approval Process ◽  
Individual Patient Response

Objective: To review and summarize topical oxymetazoline’s pharmacology, pharmacokinetics, efficacy, safety, cost, and place in therapy for persistent redness associated with erythematotelangiectatic rosacea. Data Sources: Literature searches of MEDLINE (1975 to September 2017), International Pharmaceutical Abstracts (1975 to September 2017), and Cochrane Database (publications through September 2017) using the terms rosacea, persistent redness, α -agonist, and oxymetazoline. Study Selection and Data Extraction: Results were limited to studies of human subjects, English-language publications, and topical use of oxymetazoline. Relevant materials from government sources, industry, and reviews were also included. Data Synthesis: Data support the efficacy of oxymetazoline for persistent facial redness. Little study beyond clinical trials cited in the drug approval process has been conducted. Current data suggest that oxymetazoline is similar in safety and efficacy to brimonidine. Head-to-head comparisons of topical α-agonists for erythema caused by rosacea are needed. Conclusion: The topical α-agonist, oxymetazoline, is safe and effective for reducing persistent facial redness associated with erythematotelangiectatic subtype of rosacea. Health care practitioners selecting among treatments should consider not only the subtype of rosacea but also individual patient response, preference, and cost.

scholarly journals Mifepristone as Bridge or Adjunct Therapy in the Management of Challenging Cushing Disease Cases

2021 ◽  
Vol 14 ◽  
pp. 117955142199410
Author(s):  
Alice Y Chang ◽  
Sasan Mirfakhraee ◽  
Elizabeth E King ◽  
Jennifer U Mercado ◽  
Diane M Donegan ◽  
...  
Keyword(s):  
Cushing Syndrome ◽  
Severe Disease ◽  
Disease Recurrence ◽  
Adjunctive Treatment ◽  
Therapeutic Trial ◽  
Cushing Disease ◽  
The Us ◽  
Clinical Benefits ◽  
Effects Of Radiation ◽  
Bridge Therapy

Establishing a definitive diagnosis of Cushing disease (CD), given its clinical and biochemical heterogeneity, initiating effective treatment to control the effects of hypercortisolism, and managing recurrence are challenging disease aspects to address. Mifepristone is a competitive glucocorticoid receptor antagonist that is approved in the US by the Food and Drug Administration to control hyperglycemia secondary to endogenous hypercortisolism (Cushing syndrome) in patients who have glucose intolerance or type 2 diabetes mellitus and have failed surgery or are not candidates for surgery. Herein, we describe 6 patients with CD who received mifepristone as adjunct/bridge therapy in the following clinical settings: to assess clinical benefits of treatment for suspected recurrent disease, to control hypercortisolism preoperatively for severe disease, to control hypercortisolism during the COVID-19 pandemic, and to provide adjunctive treatment to radiation therapy. The patients were treated at multiple medical practice settings. Mifepristone treatment in each of the described cases was associated with clinical improvements, including improvements in overall glycemia, hypertension, and weight loss. In addition, in one case where biochemical and radiological evidence of disease recurrence was uncertain, clinical improvement with mifepristone pointed toward likely disease recurrence. Adverse events associated with mifepristone reported in the 6 cases were consistent with those previously reported in the pivotal trial and included cortisol withdrawal symptoms, antiprogesterone effects (vaginal bleeding), hypothyroidism (treated with levothyroxine), and hypokalemia (treated with spironolactone). These cases show how mifepristone can potentially be utilized as a therapeutic trial in equivocal cases of CD recurrence; as a presurgical treatment strategy, particularly during the COVID-19 pandemic; and as bridge therapy, while awaiting the effects of radiation.

Enrollment disparities in cancer clinical trials leading to FDA approvals between 2008 and 2020.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18501-e18501
Author(s):  
Ryan Huu-Tuan Nguyen ◽  
Yomaira Silva ◽  
Vijayakrishna K. Gadi
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Clinical Trials ◽  
Drug Approval ◽  
The United States ◽  
Cancer Clinical Trials ◽  
Cancer Prevalence ◽  
Fda Approval ◽  
The Us ◽  
Enrollment Data

e18501 Background: Cancer clinical trials based in the United States (US) have lacked adequate representation of racial and ethnic minorities, the elderly, and women. Pivotal clinical trials leading to United States Food and Drug Administration (FDA) approval are often multi-national trials and may also lack generalizability to underrepresented populations in the United States. We determined the racial, ethnic, age, and sex enrollment in pivotal trials relative to the US cancer population. Methods: We reviewed the FDA’s Drug Approvals and Databases for novel and new use drug approvals for breast, colorectal, lung, and prostate cancer indications from 2008 through 2020. Drugs@FDA was searched for drug approval summaries and FDA labels to identify clinical trials used to justify clinical efficacy that led to FDA approval. For eligible trials, enrollment data were obtained from FDA approval summaries, FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. Enrollment Fraction (EF) was calculated as enrollment in identified clinical trials divided by 2017 SEER cancer prevalence. All data sources were publicly available. Results: From 2008 through 2020, 60 drugs received novel or new use drug approval for breast, colorectal, lung, or prostate cancer indications based on 66 clinical trials with a total enrollment of 36,830. North America accounted for 9,259 (31%) enrollees of the 73% of trials reporting location of enrollment. Racial demographics were reported in 78% of manuscripts, 66% of ClinicalTrials.gov pages, and 98% of FDA labels or approval summaries. Compared with a 0.4% enrollment fraction among White patients, lower enrollment fractions were noted in Hispanic (0.2%, odds ratio [OR] vs White, 0.46; 95% confidence interval [CI], 0.43 to 0.49, P< 0.001) and Black (0.1%, OR 0.29; 95% CI 0.28 to 0.31, P< 0.001) patients. Elderly patients (age ≥ 65 years) were less likely than younger patients to be enrollees (EF 0.3% vs 0.9%, OR 0.27; 95% CI 0.26 to 0.27, P< 0.001) despite accounting for 61.3% of cancer prevalence. For colorectal and lung cancer trials, females were less likely than males (EF 0.7% vs 1.1%, OR 0.66; 95% CI 0.63 to 0.68, P< 0.001) to be enrolled. Conclusions: Black, Hispanic, elderly, and female patients were less likely to enroll in cancer clinical trials leading to FDA approvals from 2008 to 2020. Race and geographic enrollment data were inconsistently reported in journal manuscripts and ClinicalTrials.gov. The lack of appropriate representation of specific patient populations in these key clinical trials limits their generalizability. Future efforts must be made to ensure equitable access, representation, and reporting of enrollees that adequately represent the US population of patients with cancer.

Together Forward?

The Last Card ◽  
2019 ◽  
pp. 74-88
Keyword(s):  
National Security ◽  
Armed Forces ◽  
Current Approach ◽  
Military Operations ◽  
Joint Chiefs Of Staff ◽  
Sectarian Violence ◽  
The Us

This chapter examines debates over US policy in the summer of 2006, focusing particularly on the unhappy results of military efforts to tamp down violence in Baghdad. Two major military operations—Operations Together Forward I and II—were launched, intended, as the chairman of the Joint Chiefs of Staff, Peter Pace, recalled, to “begin the process of turning over the battlefield responsibilities to the Iraqi armed forces.” Both were clear disappointments, however, revealing how unprepared Iraqi forces were to assume responsibility for their country's security. Iraqi forces themselves were, in the words of the National Security Council's Meghan O'Sullivan, “perpetuating acts of sectarian violence” and were “as much part of the problem as they are a solution to the problem.” Throughout the summer, NSC staff thus sought to press the Iraq country team for a review of Iraq strategy, and pushed the president to ask General George Casey, commander of Multi-National Force Iraq (MNF-I), harder questions about where the current approach was leading. However, MNF-I and the US Embassy in Iraq continued to champion existing plans, believing that the existing strategy merely required more time.

scholarly journals ONCOLYTIC VIRAL THERAPY IN CANCER THERAPEUTICS

2017 ◽  
Vol 10 (10) ◽  
pp. 96
Author(s):  
Krishnan Vengadaragava Chary ◽  
Anish Bharatwaj
Keyword(s):  
Clinical Trial ◽  
Meta Analysis ◽  
Cancer Therapeutics ◽  
Drug Approval ◽  
Clinical Trial Registry ◽  
Oncolytic Viral Therapy ◽  
Medical College ◽  
Comprehensive Information ◽  
Viral Therapy ◽  
The Us

Objective: The aim of this study is to provide comprehensive information of oncolytic viral therapy, from the origin to present scenario.Methods: This observational study was conducted by the Department of Pharmacology, Saveetha Medical College, Chennai between July and December 2016. Date regarding ongoing oncolytic virotherapy trials was retrieved from clinical trial database, United States and Clinical trial registry forum, India. Tamilnogene approval details were obtained from the US-Food and Drug Administration approval new drug approval information.Results: Eleven ongoing trials in Phase I and Ia are being carried out, of which 4 viral strains such as herpes, adenovirus, measles, and reovirus are used for intracerebral malignancies. Four trials have shown superior effects and seven trial results are yet to be completed.Conclusion: Oncolytic viral therapy can be as effective as targeted therapy in battling against cancer; however, long-term efficacy and safety should be established from more studies and meta-analysis.

scholarly journals Human response to the thermal indoor environment created by a radiant, and a combined radiant and convective cooling system

2019 ◽  
Vol 111 ◽  
pp. 02060
Author(s):  
Ongun B. Kazanci ◽  
Dolaana Khovalyg ◽  
Takayoshi Iida ◽  
Yoshitaka Uno ◽  
Tomo-oki Ukiana ◽  
...  
Keyword(s):  
Human Subject ◽  
Indoor Environment ◽  
Cooling System ◽  
Human Subjects ◽  
Whole Body ◽  
Indoor Environments ◽  
Climate Chamber ◽  
Convective Cooling ◽  
Physical Measurements ◽  
Two Systems

This study reports the main findings from a series of human subject experiments, where the subjects were exposed to the different indoor environments created by different cooling systems. The studied systems were a radiant cooling system (chilled ceiling and mixing ventilation, CCMV), and a combined radiant and convective cooling system (radiant diffuse ceiling ventilation, RDCV). The experiments were conducted in a climate chamber under controlled conditions. The climate chamber was configured as a two-person office room. 24 human subjects (12 female and 12 male) were chosen. The exposure lasted three hours and the participants were allowed to work on their own tasks (normal office work) during the exposure. The cooling load was 54 W/m2 and the room temperature at a reference location was kept constant at 26°C (summer conditions). The results show that under both systems, whole body thermal sensation was between slightly warm and neutral (closer to neutral with the RDCV system), and the overall thermal acceptability was almost the same for both systems (close to clearly acceptable). The satisfaction of the human subjects with the thermal environment was very close under the two systems; between satisfactory and slightly satisfactory (closer to satisfactory). Air movement acceptability (slightly higher and closer to clearly acceptable with the RDCV system) was also very close with the two systems. The results of the human subject experiments agree well with the physical measurements of the thermal indoor environment and confirm that the studied systems created very similar thermal indoor environments.

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