Rare Diseases Drug Development
Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow in Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
In 1992, FDA initiated the FDA Accelerated Approval Program to allow faster approval of drugs for serious conditions that fill an unmet medical need. The faster approval relies on use of surrogate endpoints. Drug approval typically requires clinical trials with endpoints that demonstrate a clinical benefit, such as increased survival for cancer patients. Drugs with accelerated approval can initially be tested in clinical trials that use a surrogate endpoint, or something that is thought to predict clinical benefit. Surrogate endpoints typically require less time, and in the case of a cancer patient, it is much faster to measure a reduction in tumor size, for example, than overall patient survival.
Breaking out of the Silos in the Heartland
Thomas S. Inui, Richard M. Frankel in Enhancing the Professional Culture of Academic Health Science Centers, 2022
At the basic end of the biomedical research spectrum, we are in the midst of enormous gains that are fundamentally transforming our understanding of human biology, with sequencing of the genome, discovery of scores of novel biochemical pathways and improved ability to elucidate the potential molecular mechanisms underlying complex human diseases. Yet, our successes at generating actual clinical interventions from these basic science gains have been steadily declining. Any major discovery at the basic level takes 10 years or more before it can become an approved drug, and then it takes an additional decade or more before such an approved therapy is integrated into routine practice.1,2 The industries that bring new discoveries into the market place as new therapies, devices, or diagnostic tests are in the midst of a crisis, with exponentially increasing costs, regulatory barriers, and long development time burdens. Furthermore, the impact of some of the innovations that do reach the market are plagued by the enormous delays in their implementation into routine disease management, due in part to limited health services and health outcomes research. From the foregoing, it was evident that biomedical research needed a paradigm shift in order to move forward. The key goal for the new paradigm was to devise methodologies that would facilitate the “translation” of research findings into practical clinical interventions.
Pharmaceuticals: Some General Aspects
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Pharmaceutical companies developing orphan drugs benefit from a variety of advantages among them reduced regulatory fees, financial support for clinical trials, and protection from competition once the medicine enters the market; the duration of marketing exclusivity for an approved drug is 7 years (USA) and 10 years, respectively. On the other hand, clinical studies on orphan drugs require a larger network of clinical operations in more than one country in order to recruit enough patients (Ku, 2015). The current status of orphan drug development in the EU and the US has been reviewed by Aronson (2006), Hall and Carlson (2014), and more recently by Giannuzzi et al. (2017), and Mezher (2017).
Expanded access to investigational drugs: balancing patient safety with potential therapeutic benefits
Published in Expert Opinion on Investigational Drugs, 2018
Elena Fountzilas, Rabih Said, Apostolia M. Tsimberidou
Recently, US Senators introduced the ‘Enhanced Clinical Trial Design Act of 2017’ to render investigational drugs more widely available to higher risk and more diverse patient populations through clinical trials [52]. They plan to update current processes to include more patients by expanding the eligibility criteria for clinical trials. Their specific aims are to (a) organize a collaboration between the FDA and the National Institutes of Health to expand inclusion study criteria, (b) carry out studies addressing the challenges of drug approval processes, (c) allow manufacturers to offer drugs on the basis of phase I data, and (d) facilitate IRB procedures. It is encouraging that the FDA has recently approved drugs/strategies for rare tumors and immunotherapeutic agents across tumor types.
N-of-1 Precision Medicine and Research Oversight
Published in The American Journal of Bioethics, 2019
Andrew Crouse, Mariko Nakano-Okuno, Matthew Might, Thomas May
Combined, this effectively leaves no standard of care for these rare genetic disorders and requires an “n-of-1 approach” for care. The Hugh Kaul Precision Medicine Institute (Hugh Kaul Precision Medicine Institute n.d.) offers a precision medicine consultation for these types of patients and others when standard of care is failing to provide relief or doesn’t yet exist. Our process intakes a medical history that often includes a molecular diagnosis and a deep review of the literature using computational tools and software we have developed to look for published therapeutic options. We often find that additional research is needed (variant functional analysis, animal model development, transcriptonomics, etc.) to fully understand the disease mechanism and coordinate with the families to facilitate that when possible. However, in some cases, we find evidence that repurposing a currently Food and Drug Administration (FDA)-approved drug could be therapeutic.
Bioidentical hormones
Published in Climacteric, 2021
F. Z. Stanczyk, H. Matharu, S. A. Winer
Briefly, some parts of the multistage process for FDA drug approval include information about the biophysical and biochemical characteristics of the drug, pharmacokinetics, proposed indication, the risks and benefits, and so on. Then preclinical testing as well as animal studies are obtained. Benefits must be shown to outweigh risks. Confirmation of the manufacturing process’s reliability is required followed by submission of an investigational new drug (IND) application. Dose–response studies and clinical trials then result in submission of a new drug application (NDA) by the pharmaceutical company or a drug sponsor. A drug is approved once safety and efficacy are demonstrated in the clinical trials. After approval, adverse event reports are used to monitor safety and continually review the drug status to protect the public. The package insert has extensive product information with efficacy and safety clearly delineated for the patient30,31.
Related Knowledge Centers
- Clinical Trial
- Drug Development
- Drug Discovery
- Regulation of Therapeutic Goods
- Medication
- Center For Drug Evaluation & Research
- Lead Compound
- Preclinical Development
- Drug Design
- Abbreviated New Drug Application