Off-label Drug Use: Fact vs. Fiction

Posted by cdavenport on Friday Aug 17, 2012 Under Drug Promotion, Drug Safety, FDA

The authors – CM Wittich, CM Burkle, and WL Lanier – offer a concise review of the topic of off-label drug use including its definition, prevalence, and implications for drug safety.   The article format addresses 10 common questions and their answers about off-label drug use.  The breadth of application, its acceptance, and the liabilities of off-label use are explored.  A history of FDA regulations surrounding the practice is presented, which helps to put its evolution into proper perspective.  Off-label use, which occurs in every medical specialty, is more common in patient populations not likely to be included in clinical trials (e.g., pediatric, pregnant, or psychiatric patients).  Once a medication is marketed, the FDA does not limit or control how the medication is prescribed by physicians. The pros and cons of the distribution of information regarding the off-label use of medications by pharmaceutical companies, the use of informed consent, and the liability of prescribing physicians are discussed.

SourceMayo Clinic Proceedings  – pdf of full article.

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Linguamatics, the leader in natural language processing (NLP)-based text mining, announced that the Federal Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) has licensed its 12E text mining platform as a discovery and decision support tool to supplement laboratory research efforts on drug safety.  The FDA will use the platform to review published literature and drug product labels to address key biomedical issues, including mechanisms of drug toxicity and disease processes.  In addition to document retrieval, the 12E platform can identify, extract, synthesize, and analyze relevant facts and relationships (e.g., between genes and diseases, drugs and side effects).  Customers include top tier commercial, academic, and governmental organizations, including 9 of the top 10 global pharmaceutical companies.  The 12E platform is available both as an in-house or cloud-based system.

Typical applications in pharmaceutical, biotechnology, and healthcare include:
•    Mapping gene-disease relationships and identifying potentially novel therapeutic targets
•    Biomarker discovery
•    Drug repurposing
•    Drug safety
•    Patent analysis
•    Clinical trial site selection and study design
•    Mining electronic medical records to improve prediction of health outcomes
•    Translational medicine
•    Competitive intelligence
•    Social media mining
•    Subjective data mining (sentiment analysis, key opinion mining)

SourcesBioSpace and Business Weekly

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FDA Pharamacogenomic Biomarker Database

Posted by cdavenport on Thursday Jul 5, 2012 Under Databases, Drug Safety, FDA, Genetic Toxicology, Regulatory

Pharmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events, and optimizing drug dose. Drug labels may contain information on genomic biomarkers and can describe:

    • Drug exposure and clinical response variability
    • Risk for adverse events
    • Genotype-specific dosing
    • Mechanisms of drug action
    • Polymorphic drug target and disposition genes

This resource table lists FDA-approved drugs with pharmacogenomic information / biomarkers in their labels.

Source:  FDA

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FDA Resource for Approved Drug Information

Posted by cdavenport on Monday Jun 25, 2012 Under Databases, FDA, Preclinical, Regulatory

Ever wanted to know the ins and outs of almost every drug approved by the Food and Drug Administration since 1939?

By using the Drugs@FDA database, you can search for information about FDA-approved brand name and generic drugs and therapeutic biological products.  The database includes most of the drug products approved since 1939 and has drug labels, patient information, approval letters, and other information for most drug products approved since 1998.

Source:  FDA

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Potential Academic Contributions to Drug Development

Posted by cdavenport on Monday May 14, 2012 Under Drug Safety, FDA, Techniques

Dr. Janet Woodcock (CDER, FDA) stated that for every 10 drugs that enter Phase I clinical trials, only 1 drug is approved.  The cost of bringing an innovative drug to market often requires a decade and a billion dollars of investment.  The paradigm where pharmaceutical companies invest heavily in research and development yet garner few drug approvals is unsustainable.

Woodcock suggests that academic researchers can contribute better methods and technologies to enable faster/better preclinical and clinical decisions to be made during drug development.  Recommendations given include:

  • Development of biomarkers that help identify not only safety risks but also identify patients most likely to benefit from a new, targeted therapy
  • Greater emphasis on applied science (e.g., drug manufacturing and scale-up enhancements)
  • Identification of biochemical pathways causal to disease states
  • Identification of proof-of-concept/surrogate endpoints
  • Enhanced understanding of how the body handles a drug
  • Take a lead on developing orphan drugs, which have historically not been a priority for pharmaceutical companies
  • Develop and implement new ways to conduct clinical trials (e.g., use of early biomarker identification to guide patient selection) with the goal of developing faster, better, smaller clinical studies to gain critical information more quickly ( e.g., work being done at Stanford University)
  • To extend clinical trials into the community and region surrounding academic medical centers to facilitate patient access, recruitment, and to enhance compliance

The public has a decreased tolerance for risk, as evidenced by increased regulatory requirements for premarket evaluation of drug safety and efficacy.  The hope is that academic researchers can drive changes in the required testing paradigms (nonclinical and clinical) to enable faster, better, and cheaper drug approvals.

Sources:  Lecture by Dr. Janet Woodcock at the California Institute for Quantitative Biosciences (qb3), UCSF and

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Evolving FDA and EMEA Collaborations

Posted by cdavenport on Monday Jan 11, 2010 Under Drug Safety, EMEA, FDA

Collaboration between the 2 of the world’s premier pharmaceutical regulatory bodies (FDA and EMEA) has increased markedly in the last few years, a process which has come largely in response to the rapid globalization of drug development, manufacturing, and production.  Distillation of an interview with Murray Lumpkin, the FDA’s Deputy Commissioner for International Programs who is spearheading the FDA’s efforts in this field, gave several succinct insights relative to the history and context of the collaboration and drug safety (preclinical and clinical) initiatives, among others.

Over the past 10-15 years, the FDA and EMEA initially focused on understanding each other’s regulatory systems.  This initiative evolved to  sharing  information (managerial and technical) since pharmaceutical companies were  submitting largely similar information to both Agencies.  The “Transatlantic Administrative Simplification Action Plan,”  a centerpiece of this relationship,  covers 4 primary areas of potential convergence: 1) quality and inspections, 2) pharmacovigilance, 3) scientific collaboration, and 4) guidelines, format harmonization,  and electronic submission.  Information is shared about applications,  questions and answers, and pre-decisional information.  Drafts of guidance and policy documents are also shared prior to publication.  We try to give each other a heads up on newsworthy items and/or something that is likely to generate questions for them.  We don’t want to blindside each other, particularly in regard to issues with a public health or safety impact.  This cooperation has led to the permanent placement of an executive in each other’s organization:  Janice Soreth (from FDA) and Hilde Boone (from EMEA).

FDA/EMEA “clusters”  in pediatrics and oncology have been particularly active, with periodic teleconferences detailing current applications and upcoming actions, challenges and difficult questions, and various meeting updates (sometimes with joint participation).  Although resolutions may differ between Agencies, there is a mutual understanding of how decisions were formulated, and an acknowledgment that similar data was evaluated by both.  Other examples of joint clusters include:  vaccines, pharmacogenomics, orphan medicines, and cardiovascular.

The potential for joint acceptance of each other’s drug approvals was discussed.  It was acknowledged that although regulatory decisions are largely science based, there are also jurisdictional componenets, such as risk tolerance, which remain largely cultural.  For this reason, mutual acceptance of drug approvals was not seen as likely in the near term.

Upcoming prospects for convergence may involve leveraging each other’s resources (e.g., GMP and GCP inspections) to reduce audit duplication.  The distinction was made that this effort would enable the Agencies to rely on each other’s information, but not necessarily on each other’s decisions.  Other areas of possible harmonization may include biomarkers (e.g., the recent joint validation of renal toxicity biomarkers), as well as trial design and comparators.  In regard to drug safety, the pharmaceutical industry has been invited to conduct a study to compare the EU and US approaches to risk management formats (e.g., E2E, Volume 9a RMP Guidance, REMS, etc.) and to identify opportunities for convergence.  In addition, other areas for possible convergence were discussed.

Source:  InPharm

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