Download - Trends in Warning and NOV Letters 2013
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Alan BergstromSenior Director, Commercial Regulatory Affairs
CBI Promotional ComplianceOctober 7, 2013
Trends in Recent Warning and NOV Letters Issued by OPDP
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The content, views, and opinions in this presentation are my own and do not in anyway represent the views or opinions of Daiichi Sankyo, Inc.
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OPDP Letters 2000 – 2013
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Professional versus Consumer Violations 2013
8 Professional – 4 websites, 1 e-mail, 2 sales aids, 1 reprint carrier
5 Consumer – 2 print ads, 2 patient brochure, 1 VNR
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Category of Violations for 2013
Omission/Minimization of Risk – 11Unsubstantiated Superiority – 5Omission of Material Fact – 5Overstatement of Efficacy – 3Unsubstantiated Claim – 2Unsubstantiated Efficacy – 2Misleading Claim – 2Promotion of Investigational Agent – 1Inadequate Communication of Indication – 1Unsubstantiated MOA – 1Failure to Submit - 1
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Is There an Evident Trend?
•Unsubstantiated Claims?•Promotion of Investigational Agents?•Press releases/VNRs?
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Unsubstantiated Claims
2010 2011 2012 2013
25/48 14/31 13/28 8/13
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What is substantial evidence?
•Evidence consisting of adequate and well-controlled investigations
•21 CFR 314.126 describes the characteristics of adequate and well-controlled trials
•21 CFR 202.1(e)(6) and (e)(7) describes multiple ways materials are or may be false and misleading
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What are some red flags to OPDP?
•Open-label studies•Post-hoc subgroup analyses•Meta-analyses•Comparative studies
From: Substantial Evidence and Other Standards, by Elaine Hu Cunningham, Senior Regulatory Review Officer ,OPDP, at DIA Marketing Pharmaceuticals 2012.
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Examples of letters for 2013
•Retrospective• Doxil website NOV dated May 22, 2013
•Meta-analysis• Marplan website NOV dated May 6, 2013
•Retrospective (in support of a Comparative Claim)• Clozapine article detailer NOV dated April 8, 2013
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Retrospective study
“The references cited to support claims onthe website concerning CA-125 consist ofretrospective evaluations of primary dataperformed in a post-hoc manner,retrospective single institution chart reviews,a retrospective sub-group analysis, andexploratory studies that cite sponsor’s dataon file. Retrospective studies and institutionalchart reviews do not constitute substantialevidence or substantial clinical experienceto support the claims and presentations…”
Unsubstantiated claim
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Meta-analysis
“The reference cited to support these claims is a publication which describes a literature review and meta-analyses examining the efficacy of several MAOIs, including isocarboxazid (Marplan). The meta-analyses …may have produced a biased sample of studies since failed or negative clinical trials are often not published in the medical literature.”
Overstatement of Efficacy
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Retrospective study
“…claims of superiority must be supportedby two adequate and well-controlled head-to-head clinical trials…”
“The study…presents the results of aretrospective Positive and NegativeSyndrome Scale (PANSS)-derived five-factor analysis of data…”“…a single, retrospective, PANSS-derivedfive-factor analysis…does not constitute substantial evidence or substantial clinical experience…”
Unsubstantiated Superiority
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Promotion of Investigational Agents
2010 2011 2012 2013
0/48 3/31 2/28 1/13
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Promotion of Investigational Agents
21 CFR 312.7 “A sponsor or investigator, or any person acting on behalf of a sponsor or investigator, shall not represent in a promotional context that an investigational new drug is safe or effective for the purposes for which it is under investigation…”
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Promotion of Investigational Agents
CBA Research Inc.
“The above referenced claims make numerous positive and definitive conclusions about CBT-1, such as its ability to reverse multi-drug resistance in cancer cells and to improve patient outcomes, while reducing the toxic side effects of chemotherapy and decreasing treatment failures.”
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Press Releases/VNRs
2010 2011 2012 2013
0/48 0/31 2/28 1/13
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Video News Release
ParaPRO LLCNatroba (spinosad) topical suspension, 0.9%•Omits ALL risk information including warnings and precautions, and the most frequently reported AEs•Unsubstantiated superiority claims – “game changing medication, one that doesn’t require nit combing to be effective”.•Fails to adequately communicate the full indication
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Key Takeaways
•Omission/minimization of risk still leads the list of violations•Unsubstantiated claims/efficacy/superiority a close second•Increased focus on investigational agents and Press Releases/VNRs (?)•Important to read the letters issued by OPDP
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Thank You
Questions?