Ensuring Timely Approval Of Generic Drugs

By Ameet Sarpatwari and Aaron S. Kesselheim

Cross posted from Health Affairs Blog

Having saved US consumers over $1.5 trillion in the past decade, generic drugs are one of the most cost-effective interventions in our entire health care system. Using generic drugs instead of brand-name drugs, when a generic is available, has been shown to increase medication adherence and improve health outcomes for chronic conditions.

Importantly, generic drugs offer these advantages without sacrificing quality; the Food and Drug Administration’s bioequivalency standards are met and often exceeded by generic-name manufacturers, and no randomized controlled trials—the gold standard of medical evidence—have identified clinically significant variations in outcomes between brand-name and FDA-approved interchangeable generic drugs.

However, to perform the tests the Food and Drug Administration (FDA) requires before approving a generic drug, manufacturers need access to one vital component: the brand-name product. Samples of the brand-name version of a drug can be used as a comparator to demonstrate the similarity of the molecular structure, or even the clinical outcomes from the generic product. Physico-chemical details about the brand-name drug, such as its molecular structure, stability, and cross-reactions, can be even more helpful in ensuring that the generic version adheres to the highest quality standards.

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Monthly Round-Up of What to Read on Pharma Law and Policy

By Ameet Sarpatwari and Aaron S. Kesselheim

Each month, members of the Program On Regulation, Therapeutics, And Law (PORTAL) review the peer-reviewed medical literature to identify interesting empirical studies, in-depth analyses, and thoughtful editorials on pharmaceutical law and policy.

Below are the papers identified from the month of February.  The selections feature topics ranging from an underreporting of deviations from good clinical practice in peer-reviewed medical journals, to the impact of risk evaluation and mitigation strategies on off-label prescribing, to repairing the broken market for antibiotic innovation.  A full posting of abstracts/summaries of these articles may be found on our website.

  1. Chambers JD, Chenoweth M, Cangelosi MJ, Pyo J, Cohen JT, Neumann PJ. Medicare is scrutinizing evidence more tightly for national coverage determinations. Health Aff (Millwood). 2015 Feb 1;34(2):253-260.
  2. Falit BP, Singh SC, Brennan TA. Biosimilar competition in the United States: statutory incentives, payers, and pharmacy benefit managers. Health Aff (Millwood). 2015 Feb 1;34(2):294-301.
  3. Hwang CS, Turner LW, Kruszewski SP, Kolodny A, Alexander GC. Prescription drug abuse: a national survey of primary care physicians. JAMA Intern Med. 2015 Feb 1;175(2):302-304.
  4. Kesselheim AS, Tan YT, Avorn J. The roles of academia, rare diseases, and repurposing in the development of the most transformative drugs. Health Aff (Millwood). 2015 Feb 1;34(2):286-293.
  5. Outterson K, Powers JH, Daniel GW, McClellan MB. Repairing the broken market for antibiotic innovation. Health Aff (Millwood). 2015 Feb 1;34(2):277-285.
  6. Rising JP, Moscovitch B. Characteristics of pivotal trials and FDA review of innovative devices. PLoS One. 2015 Feb 4;10(2):e0117235.
  7. Sarpatwari A, Franklin J, Avorn J, Seeger J, Landon J, Kesselheim A. Are risk evaluation and mitigation strategies associated with less off-label use of medications? The case of immune thrombocytopenia. Clin Pharmacol Ther. 2015 Feb;97(2):186-193.
  8. Seife C. Research misconduct identified by the US Food and Drug Administration: Out of sight, out of mind, out of the peer-reviewed literature. JAMA Intern Med. 2015 Feb 9. [Epub ahead of print]

  9. Wang B, Liu J, Kesselheim AS. Variations in Time of Market Exclusivity Among Top-Selling Prescription Drugs in the United States. JAMA Intern Med. 2015 Feb 9. [Epub ahead of print]
  10. Zetterqvist AV, Merlo J, Mulinari S. Complaints, complainants, and rulings regarding drug promotion in the United kingdom and sweden 2004-2012: a quantitative and qualitative study of pharmaceutical industry self-regulation. PLoS Med. 2015 Feb 17;12(2):e1001785.

Monthly Round-Up of What to Read on Pharma Law and Policy

By Ameet Sarpatwari and Aaron S. Kesselheim

Each month, members of the Program On Regulation, Therapeutics, And Law (PORTAL) review the peer-reviewed medical literature to identify interesting empirical studies, in-depth analyses, and thoughtful editorials on pharmaceutical law and policy.

Below are the papers identified from the month of January.  The selections feature topics ranging from the trend in lag-time between FDA approval of drugs and published cost-utility evidence; to practical, legal, and ethical issues with expanded access to investigational drugs; to the use of tiered formularies to discriminate against patients with HIV in the federal marketplace.  A full posting of abstracts/summaries of these articles may be found on our website.

  1. Aliferis L. Variation in prices for various medical tests and procedures. JAMA Intern Med. 2015 Jan 1;175(1):11-12.
  2. Chambers JD, Thorat T, Pyo J, Neumann PJ. The lag from FDA approval to published cost-utility evidence. Expert Rev Pharmacoecon Outcomes Res. 2015 Jan 12:1-4.
  3. Darrow JJ, Sarpatwari A, Avorn J, Kesselheim AS. Practical, legal, and ethical issues in expanded access to investigational drugs. New Eng J Med. 2015 Jan 15;372(3):279-286.
  4. Drazen JM. Sharing individual patient data from clinical trials. New Eng J Med. 2015 Jan 15;372(3):201-202.
  5. Jacobs DB, Sommers BD. Using drugs to discriminate—adverse selection in the insurance marketplace. New Eng J Med. 2015 Jan 29;372(5):399-402.
  6. Moses H 3rd, Matheson DH, Cairns-Smith S, George BP, Palisch C, Dorsey ER. The anatomy of medical research: US and international comparisons. BMJ. 2015 Jan 28;350:h522. JAMA. 2015 Jan 13;313(2):174-189.
  7. Rajan PV, Kramer DB, Kesselheim AS. Medical device postapproval safety monitoring: where does the United States stand? Circ Cardiovasc Qual Outcomes. 2015 Jan;8(1):124-131.
  8. Ryskina KL, Halpern SD, Minyanou NS, Goold SD, Tilburt JC. The Role of Training Environment Care Intensity in US Physician Cost Consciousness. Mayo Clin Proc. 2015 Jan 26. pii: S0025-6196(14)01083-1090.
  9. Sharfstein J. FDA Regulation of Laboratory-Developed Diagnostic Tests: Protect the Public, Advance the Science. JAMA. 2015 Jan 5. [Epub ahead of print]

Call for Postdoctoral Fellowship Applications: The Harvard Medical School/Brigham and Women’s Hospital Program On Regulation, Therapeutics, And Law (PORTAL)

By Ameet Sarpatwari and Aaron S. Kesselheim

The Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital Department of Medicine and Harvard Medical School invites its 2015 round of applications for postdoctoral fellows in pharmaceutical law and health services research.  Current fellows have studied FDA regulation, patents and drug access and costs, and competition in the therapeutic marketplace.  Other areas of focus include intellectual property, ethics, and comparative effectiveness, as well as the development, approval, and evidence-based use of drugs, devices, vaccines, procedures, and diagnostics.

Applications are invited from researchers with doctoral degrees (J.D., M.D., Ph.D., Pharm.D., or equivalent) or who will complete such training by July 2015.  Fellows will have an appointment at Harvard Medical School, receive close mentorship from faculty members in the Division, and engage in one or more projects intended to start their careers in law and public health research.  Fellowship length will vary depending on the candidate (min: 1 year).

The deadline is February 20, 2015.  To apply, please send to akesselheim@partners.org: (1) a CV, (2) a writing sample, and (3) a cover letter describing your past work, ideas for the kind of research you’d like to do in the fellowship, and career goals.

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Monthly Round-Up of What to Read on Pharma Law and Policy

By Ameet Sarpatwari and Aaron S. Kesselheim

Each month, the Program On Regulation, Therapeutics, And Law (PORTAL) in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital/Harvard Medical School reviews the peer-reviewed medical literature to identify interesting empirical studies, in-depth analyses, and thoughtful editorials on pharmaceutical law and policy.

Below are the papers identified from December. The selections feature topics ranging from access to clinical trials data, to pharmacy-based interventions to reduce primary medication non-adherence, to the impact of out-of-pocket spending caps on the non-elderly with private group health insurance. A full posting of abstracts/summaries of these articles may be found on our website.

  1. Bonini S, Eichler HG, Wathion N, Rasi G. Transparency and the European Medicines Agency—sharing of clinical trial data. N Engl J Med. 2014 Dec 25;371(26):2452-2455.
  2. Fischer MA, Choudhry NK, Bykov K, Brill G, Bopp G, Wurst AM, Shrank WH. Pharmacy-based interventions to reduce primary medication nonadherence to cardiovascular medications. Med Care. 2014 Dec;52(12):1050-1054.
  3. Kesselheim AS, Huybrechts KF, Choudhry NK, Fulchino LA, Isaman DL, Kowal MK, Brennan TA. Prescription Drug Insurance Coverage and Patient Health Outcomes: A Systematic Review. Am J Public Health. 2014 Dec 18:e1-e14. [Epub ahead of print]

  4. Nissen SE. Commentary: Confidentiality of interim trial data-The emerging crisis. Clin Trials. 2014 Dec 18. [Epub ahead of print]

  5. Notenboom K, Beers E, van Riet-Nales DA, Egberts TC, Leufkens HG, Jansen PA, Bouvy ML. Practical Problems with Medication Use that Older People Experience: A Qualitative Study. J Am Geriatr Soc. 2014 Dec;62(12):2339-2344.

  6. Riggs KR, Buttorff C, Alexander GC. Impact of Out-of-Pocket Spending Caps on Financial Burden of those with Group Health Insurance. J Gen Intern Med. 2014 Dec 4. [Epub ahead of print]

  7. Zarin DA, Tse T, Sheehan J. The Proposed Rule for U.S. Clinical Trial Registration and Results Submission.N Engl J Med. 2014 Dec 24. [Epub ahead of print]

Monthly Round-Up of What to Read on Pharma Law and Policy

By Ameet Sarpatwari and Aaron S. Kesselheim

Each month, the Program On Regulation, Therapeutics, And Law (PORTAL) in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital/Harvard Medical School reviews the peer-reviewed medical literature to identify interesting empirical studies, in-depth analyses, and thoughtful editorials on pharmaceutical law and policy.

Below are the papers identified from November. The selections feature topics ranging from the use of e-prescribing defaults to promote physician prescribing of generic drugs, to the characteristics of post-approval studies of medical devices ordered by the FDA, to a comparison of existing and emerging accelerated access pathways in the United States, European Union, Canada, and Singapore. A full posting of abstracts/summaries of these articles may be found on our website.

  1. Alpern JD, Stauffer WM, Kesselheim AS. High-cost generic drugs–implications for patients and policymakers. N Engl J Med. 2014 Nov 13;371(20):1859-62.
  2. Baird LG, Banken R, Eichler HG, Kristensen FB, Lee DK, Lim JC, Lim R, Longson C, Pezalla E, Salmonson T, Samaha D, Tunis S, Woodcock J, Hirsch G. Accelerated access to innovative medicines for patients in need. Clin Pharmacol Ther. 2014 Nov;96(5):559-71.
  3. Becker JE, Ross JS. Reporting Discrepancies Between the ClinicalTrials.gov Results Database and Peer-Reviewed Publications. Ann Intern Med. 2014 Nov 18;161(10):760.
  4. Gagne JJ, Thompson L, O’Keefe K, Kesselheim AS. Innovative research methods for studying treatments for rare diseases: methodological review. BMJ. 2014 Nov 24;349:g6802.
  5. Lexchin J. Postmarket safety warnings for drugs approved in Canada under the Notice ofCompliance with conditions policy. Br J Clin Pharmacol. 2014 Nov 12. [Epub ahead of print]
  6. Manz C, Ross JS, Grande D. Marketing to physicians in a digital world. N Engl J Med. 2014 Nov 13;371(20):1857-9.
  7. Patel MS, Day S, Small DS, Howell JT 3rd, Lautenbach GL, Nierman EH, Volpp KG. Using Default Options Within the Electronic Health Record to Increase the Prescribing of Generic-Equivalent Medications: A Quasi-experimental Study. Ann Intern Med. 2014 Nov 18;161(10 Suppl):S44-52.
  8. Reynolds IS, Rising JP, Coukell AJ, Paulson KH, Redberg RF. Assessing the Safety and Effectiveness of Devices After US Food and Drug Administration Approval: FDA-Mandated Postapproval Studies. JAMA Intern Med. 2014 Nov 1;174(11):1773-9.
  9. Vermeer NS, Spierings I, Mantel-Teeuwisse AK, Straus SM, Giezen TJ, Leufkens HG, Egberts TC, De Bruin ML. Traceability of biologicals: present challenges in pharmacovigilance. Expert Opin Drug Saf. 2014 Nov 5:1-10. [Epub ahead of print]
  10. Woloshin S, Schwartz LM, Frankel B, Faerber A. US Food and Drug Administration and design of drug approval studies. JAMA. 2014 Nov 26;312(20):2163-5.

New BoH Feature: Monthly Round-Up of What to Read on Pharma Law and Policy

By Ameet Sarpatwari and Aaron S. Kesselheim

Each month, the Program On Regulation, Therapeutics, And Law (PORTAL) in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital/Harvard Medical School reviews the peer-reviewed medical literature to identify interesting empirical studies, in-depth analyses, and thoughtful editorials on pharmaceutical law and policy.  We are thrilled to announce that PORTAL (specifically Aaron Kesselheim and Ameet Sarpatwari) will being posting these curated round-ups at Bill of Health each month, with a full posting including abstracts/summaries at their website.

Below are the abstracts/summaries for papers identified from October.  The selections feature topics ranging from the cost-utility of specialty drugs, to the association between financial conflicts of interest and favorable assessments of newer influenza treatments, to the clinical evidence supporting biomarker testing reported in FDA drug labels.  We thank Lara Maggs and Nazleen Khan for their contributions to this review.

  1. Chambers JD, Thorat T, Pyo J, Chenoweth M, Neumann PJ. Despite high costs, specialty drugs may offer value for money comparable to that of traditional drugs. Health Aff (Millwood). 2014 Oct 1;33(10):1751-60.
  2. Chang CQ, Tingle SR, Filipski KK, Khoury MJ, Lam TK, Schully SD, Ioannidis JP. An overview of recommendations and translational milestones for genomic tests in cancer. Genet Med. 2014 Oct 23. [Epub ahead of print]
  3. Dunn AG, Arachi D, Hudgins J, Tsafnat G, Coiera E, Bourgeois FT. Financial conflicts of interest and conclusions about neuraminidase inhibitors for influenza: an analysis of systematic reviews. Ann Intern Med. 2014 Oct 7;161(7):513-8.
  4. Kesselheim AS, Tan YT, Darrow JJ, Avorn J. Existing FDA pathways have potential to ensure early access to, and appropriate use of, specialty drugs. Health Aff (Millwood). 2014 Oct 1;33(10):1770-8.
  5. Miladinovic B, Kumar A, Mhaskar R, Djulbegovic B. Benchmarks for detecting ‘breakthroughs’ in clinical trials: empirical assessment of the probability of large treatment effects using kernel density estimation. BMJ Open. 2014 Oct 21;4(10):e005249.
  6. Naci H, Alexander GC. Regulators should better leverage effectiveness standards to enhance drug value. Pharmacotherapy. 2014 Oct;34(10):1005-11.
  7. Sarpatwari A, Kesselheim AS, Malin BA, Gagne JJ, Schneeweiss S. Ensuring patient privacy in data sharing for postapproval research. N Engl J Med. 2014 Oct 23;371(17):1644-9.
  8. Starner CI, Alexander GC, Bowen K, Qiu Y, Wickersham PJ, Gleason PP. Specialty drug coupons lower out-of-pocket costs and may improve adherence at the risk of increasing premiums. Health Aff (Millwood). 2014 Oct 1;33(10):1761-9.
  9. Wang B, Canestaro WJ, Choudhry NK.Clinical Evidence Supporting Pharmacogenomic Biomarker Testing Provided in US Food and Drug Administration Drug Labels.JAMA Intern Med. 2014 Oct 13. [Epub ahead of print]
  10. Woodcock J. Paving the critical path of drug development: the CDER perspective. Nat Rev Drug Discov. 2014 Oct 31;13(11):783-4.
  11. Yeh JS, Austad KE, Franklin JM, Chimonas S, Campbell EG, Avorn J, Kesselheim AS. Association of medical students’ reports of interactions with the pharmaceutical and medical device industries and medical school policies and characteristics: a cross-sectional study. PLoS Med. 2014 Oct 14;11(10):e1001743.

Introducing New Blogger Ameet Sarpatwari

AmeetAmeet Sarpatwari, J.D., Ph.D., is a research fellow at Harvard Medical School and member of the Program On Regulation, Therapeutics, And Law (PORTAL) [Twitter: @PORTAL_Research] in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital. His research draws upon his interdisciplinary training as an epidemiologist and lawyer and focuses on the effects of laws and regulations on therapeutic development, approval, use, and related public health outcomes.

Ameet graduated from the University of Virginia, where he was a Jefferson Scholar. He studied epidemiology at the University of Cambridge, receiving an M.Phil. in 2006 and a Ph.D. in 2010. His doctoral work centered on uncovering disease progression, treatment effectiveness, and co-morbid burden among adults patients with primary immune thrombocytopenia—a rare autoimmune disease—through the establishment of a national disease registry. He subsequently studied law at the University of Maryland, with a focus on health law, as a John L. Thomas Leadership Scholar, graduating in 2013.

Ameet’s work has appeared in such top peer-reviewed medical journals as the New England Journal of Medicine, Clinical Pharmacology and Therapeutics, and Blood.  He is the recipient of Robert Wood Johnson Public Health Law Research grant to examine the public health implications of variation in state drug product selection laws. Among other projects, he is also currently assessing the impact of risk evaluation and mitigation strategies on competition and off-label prescribing, and legal and ethical issues surrounding the use of financial incentives to promote physician use of generic drugs.

Welcome, Ameet!