Right to Experimental Treatment: FDA New Drug Approval, Constitutional Rights, and the Public's Health

2009 ◽  
Vol 37 (2) ◽  
pp. 269-279 ◽  
Author(s):  
Elizabeth Weeks Leonard
Keyword(s):  
Treatment Options ◽  
Terminally Ill ◽  
Experimental Treatment ◽  
Drug Approval ◽  
New Drugs ◽  
Constitutional Rights ◽  
Court Of Appeals ◽  
Fda Approval ◽  
Life Saving ◽  
Constitutional Right

Do terminally ill patients who have exhausted all other available, government-approved treatment options have a constitutional right to experimental treatment that may prolong their lives? On May 2, 2006, a divided panel of the U.S. Court of Appeals for the District of Columbia, in a startling opinion, Abigail Alliance for Better Access to Developmental Drugs v. Von Eschenbach, held “Yes.” The plaintiffs, Abigail Alliance for Better Access to Developmental Drugs (Abigail Alliance) and Washington Legal Foundation, sought to enjoin the Food and Drug Administration (FDA) from refusing to allow the sale of investigational new drugs that had not yet received FDA approval. The terminally ill plaintiffs contended that they quite literally could not wait that long for the drugs. With no other treatment options available, the plaintiffs urged the court to recognize a fundamental, constitutional right to take potentially life-saving or life-prolonging drugs, even though the treatment had not been fully tested through human trials for safety and effectiveness and could not be legally marketed to the public.

New Drugs of 2012: A Concise Overview of the NMEs and Trends for Innovative Brand Market in the United States

2013 ◽  
Vol 6 (2) ◽  
pp. 2009-2013
Author(s):  
D Samba Reddy
Keyword(s):  
Drug Approval ◽  
The United States ◽  
New Drugs ◽  
New Combination ◽  
Drug Status ◽  
Combination Drug ◽  
Human Cord Blood ◽  
Life Saving ◽  
Genomics And Proteomics ◽  
The Face

Thirty-nine (39) new drugs have been approved by the U.S. FDA in 2012, a record highest number of approvals since 1996. The record is a sign that pharma companies are poised to tap recent advances from genomics and proteomics. This list includes novel new drugs, known as new molecular entities (NMEs), biologics and new products. Many life-saving drugs are approved for marketing. The list includes a total of 10 drugs for cancer treatment, and nearly a quarter of those approved in 2012 had orphan drug status.  Among the breakthrough drugs approved in 2012 were ivacaftor (cystic fibrosis), vasmodegib (skin cancer), HPC-C (human cord blood product), ruxolitinib (myelofibrosis) and a new combination drug to treat HIV. In addition,  several unique products were approved for the treatment of macular degeneration, chronic weight management, overactive bladder, actinic keratosis, erectile dysfunction, glaucoma, respiratory distress syndrome, and COPD. The approval of 39 drugs in 2012 underscores a robust success rate and confirms that innovation is once again beginning to pay off. In the existing climate of reduced revenues in the face of generic competitions, the future and survival of big companies rests heavily on their unique niche products. It is apparent that big Pharma and a growing number of emerging Biotechs alike have focused their attention on developing new NMEs for rare diseases. In 2012, the length of the FDA’s review is shorter than agencies in other countries. Innovative models adopted for R&D strategies, communications, and new regulatory changes appear to shorten development timelines. Despite record drug approvals, there is bleak scope for blockbusters because most of these drugs have a limited market. The pipeline for blockbusters appears very low. However, there is unmet medical need for new drugs in autism, Alzheimer’s disease and epilepsy. Overall, the new drug approval list unveils unique and reemerging trends indicating that the pharma companies are poised for big growth from new brands approved for marketing for narrow-spectrum indications.    

scholarly journals Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e017917 ◽  
Author(s):  
Jennifer E Miller ◽  
Marc Wilenzick ◽  
Nolan Ritcey ◽  
Joseph S Ross ◽  
Michelle M Mello
Keyword(s):  
Clinical Trial ◽  
Descriptive Analysis ◽  
Drug Level ◽  
Drug Approval ◽  
Securities And Exchange Commission ◽  
New Drugs ◽  
Pharmaceutical Companies ◽  
Cross Sectional ◽  
Fda Approval ◽  
Approved Drugs

ObjectivesTo define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs.DesignCross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies.Data sourcesData from over 45 sources, including [email protected], ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers.Outcome measuresTrial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level.ResultsThe FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries.ConclusionsAmong large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress.

The FDA’s Accelerated Approval Process: Does the Pharmaceutical Industry Have Adequate Incentives for Self-Regulation?

1999 ◽  
Vol 25 (4) ◽  
pp. 543-568
Author(s):  
Vivian I. Orlando
Keyword(s):  
Self Regulation ◽  
Immune Deficiency Syndrome ◽  
Drug Approval ◽  
Deficiency Syndrome ◽  
New Drugs ◽  
Approval Process ◽  
Advocacy Organizations ◽  
Fda Approval ◽  
Primary Responsibility ◽  
Drug Approval Process

Prompted by criticisms of long delays in its drug approval processes, the Food and Drug Administration (FDA or the Administration) took a number of measures in recent years to expedite access and increase availability of new drugs for terminally ill patients. These reforms began in the late 1980s, as acquired immune deficiency syndrome (AIDS) advocacy organizations openly criticized the FDA, noting that its policies were insufficient to address the prevalence of AIDS and the lag time for FDA approval of new AIDS treatments. The FDA's primary responsibility is to promote efficacy and ensure safety of new drugs. Consequently, the FDA must balance patients' desires to obtain new medications to treat serious and lifethreatening illnesses against government's desires to protect patients from abuses of the new drug approval process. The structure of the FDA's regulatory procedures is, therefore, essential to providing safe, effective medical treatments to patients. FDA regulations and guidelines set forth standards and practices that pharmaceutical companies must follow to gain approval of newly developed drugs.

scholarly journals Repurposing existing drugs for new uses: a cohort study of the frequency of FDA-granted new indication exclusivities since 1997

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Babak Sahragardjoonegani ◽  
Reed F. Beall ◽  
Aaron S. Kesselheim ◽  
Aidan Hollis
Keyword(s):  
Therapeutic Potential ◽  
Drug Repurposing ◽  
Status Quo ◽  
New Drugs ◽  
Generic Entry ◽  
Small Molecule Drugs ◽  
Clinical Investigations ◽  
Fda Approval ◽  
Limited Duration ◽  
Observation Period

Abstract Background Drug repurposing (i.e., finding novel uses for existing drugs) is essential for maximizing medicines’ therapeutic utility, but obtaining regulatory approval for new indications is costly. Policymakers have therefore created temporary indication-specific market exclusivities to incentivize drug innovators to run new clinical investigations. The effectiveness of these exclusivities is poorly understood. Objective To determine whether generic entry impacts the probability of new indication additions. Methods For a cohort of all new small-molecule drugs approved by the FDA between July 1997 and May 2020, we tracked new indications added for the subset of drugs that experienced generic entry during the observation period and then analyzed how the probability of a new indication changed with the number of years since/to generic entry. Results Of the 197 new drugs that subsequently experienced generic entry, only 64 (32%) had at least one new indication added. The probability of a new indication addition peaked above 4% between 7 and 8 years prior to generic entry and then to dropped to near zero 15 years after FDA approval. We show that the limited duration of exclusivity reduces the number of secondary indications significantly. Conclusion Status quo for most drug innovators is creating novel one-indication products. Despite indication-specific exclusivities, the imminence of generic entry still has a detectable impact on reducing the chances of new indication additions. There is much room for improvement when it comes to incentivizing clinical investigations for new uses and unlocking existing medicines’ full therapeutic potential.

scholarly journals The Challenging but Imperative Path to Monoclonal Antibody Use Against COVID-19 for a Small Overseas Military Hospital

2021 ◽  
Author(s):  
Spencer Shirk ◽  
Danielle Kerr ◽  
Crystal Saraceni ◽  
Garret Hand ◽  
Michael Terrenzi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hospital Admissions ◽  
Adverse Outcomes ◽  
Lessons Learned ◽  
Military Hospital ◽  
Clinical Criteria ◽  
Fda Approval ◽  
Life Saving ◽  
Set Up ◽  
Naval Hospital

ABSTRACT Upon the U.S. FDA approval in early November for a monoclonal antibody proven to potentially mitigate adverse outcomes from coronavirus disease 2019 (COVID-19) infections, our small overseas community hospital U.S. Naval Hospital Rota, Spain (USNH Rota) requested and received a limited number of doses. Concurrently, our host nation, which previously had reported the highest number of daily deaths from COVID-19, was deep within a second wave of infections, increasing hospital admissions, near intensive care unit capacity, and deaths. As USNH Rota was not normally equipped for the complex infusion center required to effectively deliver the monoclonal antibody, we coordinated a multi-directorate and multidisciplinary effort in order to set up an infusion room that could be dedicated to help with our fight against COVID. Identifying a physician team lead, with subject matter experts from nursing, pharmacy, facilities, and enlisted corpsmen, our team carefully ensured that all requisite steps were set up in advance in order to be able to identify the appropriate patients proactively and treat them safely with the infusion that has been clinically proven to decrease hospital admissions and mortality. Additional benefits included the establishment of an additional negative pressure room near our emergency room for both COVID-19 patients and, when needed, the monoclonal antibody infusion. In mid-January, a COVID-19-positive patient meeting the clinical criteria for monoclonal antibody infusion was safely administered this potentially life-saving medication, a first for small overseas hospitals. Here, we describe the preparation, challenges, obstacles, lessons learned, and successful outcomes toward effectively using the monoclonal antibody overseas.

scholarly journals Medication of Hydroxychloroquine, Remdesivir and Convalescent Plasma during the COVID-19 Pandemic in Germany—An Ethical Analysis

2021 ◽  
Vol 18 (11) ◽  
pp. 5685
Author(s):  
Katja Voit ◽  
Cristian Timmermann ◽  
Florian Steger
Keyword(s):  
Early Stage ◽  
Treatment Options ◽  
Drug Distribution ◽  
Experimental Treatment ◽  
Ethical Analysis ◽  
Ethical Principles ◽  
Ethical Challenges ◽  
Ethical Guidelines ◽  
Negative Effects ◽  
Experimental Drug

This paper aims to analyze the ethical challenges in experimental drug use during the early stage of the COVID-19 pandemic, using Germany as a case study. In Germany uniform ethical guidelines were available early on nationwide, which was considered as desirable by other states to reduce uncertainties and convey a message of unity. The purpose of this ethical analysis is to assist the preparation of future guidelines on the use of medicines during public health emergencies. The use of hydroxychloroquine, remdesivir and COVID-19 convalescent plasma in clinical settings was analyzed from the perspective of the ethical principles of beneficence, non-maleficence, justice and autonomy. We observed that drug safety and drug distribution during the pandemic affects all four ethical principles. We therefore recommend to establish ethical guidelines (i) to discuss experimental treatment options with patients from all population groups who are in urgent need, (ii) to facilitate the recording of patient reactions to drugs in off-label use, (iii) to expand inclusion criteria for clinical studies to avoid missing potentially negative effects on excluded groups, and (iv) to maintain sufficient access to repurposed drugs for patients with prior conditions.

scholarly journals Real-World Evidence of Caplacizumab Use in the Management of Acute TTP

Blood ◽  
2020 ◽  
Author(s):  
Tina Dutt ◽  
Rebecca J Shaw ◽  
Matthew James Stubbs ◽  
Jun Yong ◽  
Benjamin Bailiff ◽  
...  
Keyword(s):  
Platelet Count ◽  
Real World ◽  
Patient Characteristics ◽  
Patient Access Scheme ◽  
Fda Approval ◽  
Immune Mediated ◽  
Real World Evidence ◽  
Life Saving ◽  
The Uk ◽  
Von Willebrand

The cornerstone of life-saving therapy in immune mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody, trialled in two multicentre, randomised-placebo-controlled trials leading to EU and FDA approval, has been available in the UK through a patient-access scheme. Data was collected retrospectively from 2018-2020 for 85 patients receiving caplacizumab, including 4 children, from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial endpoints and historical outcomes in the pre-caplacizumab era. 84/85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalisation (3 days), duration of PEX (7 days) and hospital stay (12 days) was comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalisation was favourable compared with historical outcomes (p<0.05). TTP recurrence occurred in 5/85 patients; all with persistent ADAMTS13 activity <5iu/dL. Of 31 adverse events in 26 patients, 17/31 (55%) were bleeding episodes and 5/31 (16%) were thrombotic events (two unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4/5 deaths caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients receiving caplacizumab outside clinical trials, including paediatric patients. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

scholarly journals Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 909
Author(s):  
Krzysztof Kotowski ◽  
Jakub Rosik ◽  
Filip Machaj ◽  
Stanisław Supplitt ◽  
Daniel Wiczew ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Treatment Options ◽  
Protein Structures ◽  
New Drugs ◽  
Proliferating Cells ◽  
Cancer Tissues ◽  
The Impact ◽  
Rate Limiting ◽  
Synthesis And Degradation

Glycolysis is a crucial metabolic process in rapidly proliferating cells such as cancer cells. Phosphofructokinase-1 (PFK-1) is a key rate-limiting enzyme of glycolysis. Its efficiency is allosterically regulated by numerous substances occurring in the cytoplasm. However, the most potent regulator of PFK-1 is fructose-2,6-bisphosphate (F-2,6-BP), the level of which is strongly associated with 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase activity (PFK-2/FBPase-2, PFKFB). PFK-2/FBPase-2 is a bifunctional enzyme responsible for F-2,6-BP synthesis and degradation. Four isozymes of PFKFB (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) have been identified. Alterations in the levels of all PFK-2/FBPase-2 isozymes have been reported in different diseases. However, most recent studies have focused on an increased expression of PFKFB3 and PFKFB4 in cancer tissues and their role in carcinogenesis. In this review, we summarize our current knowledge on all PFKFB genes and protein structures, and emphasize important differences between the isoenzymes, which likely affect their kinase/phosphatase activities. The main focus is on the latest reports in this field of cancer research, and in particular the impact of PFKFB3 and PFKFB4 on tumor progression, metastasis, angiogenesis, and autophagy. We also present the most recent achievements in the development of new drugs targeting these isozymes. Finally, we discuss potential combination therapies using PFKFB3 inhibitors, which may represent important future cancer treatment options.

scholarly journals The Modern Landscape of Endocrine Therapy for Premenopausal Women with Breast Cancer

Breast Care ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. 312-315 ◽  
Author(s):  
Lorenzo Rossi ◽  
Olivia Pagani
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Treatment Options ◽  
Endocrine Resistance ◽  
Premenopausal Women ◽  
New Drugs ◽  
Fine Tuning ◽  
Individual Risk ◽  
Ovarian Function Suppression

The optimal endocrine therapy for premenopausal women with early and advanced breast cancer still remains an important and controversial issue. For over 30 years, tamoxifen has been the gold standard in the adjuvant setting. New therapeutic options, such as the addition of ovarian function suppression to oral endocrine therapy (either tamoxifen or aromatase inhibitors), can improve outcomes over tamoxifen alone in well-selected patients. Treatment duration has also been revisited, and extended therapy is becoming a new standard of care, especially in high-risk patients. Endocrine therapy for advanced disease still represents a challenge and a research priority. New drugs and combinations able to overcome endocrine resistance are at the horizon, and their role in premenopausal women should be better elucidated. Side effects and quality of life (including family planning considerations) play an important role in treatment selection and in the patients' treatment adherence and should always be discussed before start of treatment. The paper will specifically focus on how to integrate all new treatment options in the current armamentarium of endocrine therapy of premenopausal women, with the aim of best fine-tuning treatment selections according to the individual risk/benefit evaluation.

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.

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