1. Misleading Ads & FDA Warnings ©PharmedOut 2013 Georgetown University Medical Center Part of the Drug Ads Exercise Presentation Series

2. Disclaimer: Intellectual Property In this presentation, you will notice that we use images of many registered trademarks, many branded drug trade names, and many copyrighted advertisements -- from many different business concerns -- including drug companies, marketing consultants and medical journals. All of the intellectual property contained therein is, and remains, the exclusive intellectual property of the respective owners. Each image is used for the purpose of educational, and critical, analysis. No endorsement of any position articulated in this presentation should be inferred from the appearance of any brand, trademark, trade name or ad copy herein. This presentation has been designed with the intent to qualify for the doctrine of "fair use" -- as to these pieces of intellectual property -- under the law of the United States.

3. FDA Terms Used in Letters* 1.Unsubstantiated Superiority/Overstatement of Efficacy Claims 2.Omission of Risk Information 3.Minimization of Risk Information 4.Broadening of Indication 5.Use of Outdated Product Labeling *The following explanations of FDA terms have been paraphrased.

4. Unsubstantiated Superiority/Overstatement of Efficacy Claims An implication is made that a drug is better or more effective without supporting scientific evidence

5. Boniva Boniva Osteoporosis Treatment Print Ad

7. Boniva: Overstatement of Efficacy Boniva: Overstatement of Efficacy Claim: “Studies show, after a year on Boniva, 9 out of 10 women stopped and reversed their bone loss.” FDA Comments About Print Ad: The clinical study that served for the basis of approval… was designed to assess the percent change from baseline in lumbar BMD [bone mineral density] at 1 year. The clinical study that served for the basis of approval… was designed to assess the percent change from baseline in lumbar BMD [bone mineral density] at 1 year. This claim is based on a… per-protocol post-hoc analysis of a secondary efficacy endpoint… at the lumbar spine, total hip, trochanter, and femoral neck… that the clinical study was not adequately designed to evaluate. This claim is based on a… per-protocol post-hoc analysis of a secondary efficacy endpoint… at the lumbar spine, total hip, trochanter, and femoral neck… that the clinical study was not adequately designed to evaluate.

8. Omission of Risk Information The exclusion of important risks and consequences that may occur with approved use of a drug

9. Exforge (amlodipine and valsartan) Exforge (amlodipine and valsartan) Antihypertensive Patient Brochure

10. Exforge: Omission of Risk Information FDA Comments About Patient Brochure: The brochure fails to reveal Warnings and Precautions regarding hepatic impairment and interactions with potassium sparing diuretics, potassium supplements, or salt substitutes containing potassium. The brochure fails to reveal Warnings and Precautions regarding hepatic impairment and interactions with potassium sparing diuretics, potassium supplements, or salt substitutes containing potassium.

11. Minimization of Risk Information While risk information is presented, it is difficult to find, see, or read in comparison to information on effectiveness

12. Gelnique (oxybutynin chloride) Overactive Bladder Treatment Efficacy Claims Risk Info Restroom Stall Poster at Conference

13. Gelnique: Minimization of Risk Information Claim: “Smart gel technology is her weapon…” FDA Comments About Restroom Stall Poster: The stall cling… presents efficacy claims and presentations in large, bold, and colorful font and graphics… surrounded by a significant amount of space. The stall cling… presents efficacy claims and presentations in large, bold, and colorful font and graphics… surrounded by a significant amount of space. In contrast, the risk information is relegated to the bottom… and written in white text on a purple background in an extremely small font size and in single-spaced paragraph format, making this information very difficult to read. In contrast, the risk information is relegated to the bottom… and written in white text on a purple background in an extremely small font size and in single-spaced paragraph format, making this information very difficult to read. This presentation… fails to convey this important risk information with a prominence and readability… comparable to the claims of effectiveness. In addition, the most common adverse events are presented before more serious risks. This presentation… fails to convey this important risk information with a prominence and readability… comparable to the claims of effectiveness. In addition, the most common adverse events are presented before more serious risks.

14. Broadening of Indication The suggestion that a drug is more effective and/or capable of treatment outcomes in more conditions or patients than scientific evidence supports.

15. AzaSite (azithromycin) AzaSite (azithromycin) Ocular Antibacterial Journal Ad

17. AzaSite: Broadening of Indication Claim: “AzaSite can restore a healthy ocular surface.” FDA Comments About Journal Ad: AzaSite is indicated only for the treatment of bacterial conjunctivitis. AzaSite is indicated only for the treatment of bacterial conjunctivitis. The… presentation… suggests that AzaSite is indicated to treat any condition that causes ocular surface damage, which could include viral conjunctivitis (pinkeye), chemical injury, blepharitis, dry eye disease, and ocular rosacea, when such has not been demonstrated by substantial evidence or substantial clinical experience. The… presentation… suggests that AzaSite is indicated to treat any condition that causes ocular surface damage, which could include viral conjunctivitis (pinkeye), chemical injury, blepharitis, dry eye disease, and ocular rosacea, when such has not been demonstrated by substantial evidence or substantial clinical experience.

18. Use of Outdated Product Labeling Distribution of outdated information about a drug.

19. Voucher Tent Card Package Insert (PI) Uroxatral (alfuzosin) Uroxatral (alfuzosin) Treatment for Symptoms of Benign Prostatic Hyperplasia

20. Uroxatral: Use of Outdated Product Labeling FDA Comments about Tent Card: The most current version of the FDA- approved PI as of February 24, 2009 was the July 23, 2008 version, not the April 2007 version. The most current version of the FDA- approved PI as of February 24, 2009 was the July 23, 2008 version, not the April 2007 version.

21. Other examples

22. Copaxone (glatiramer acetate) Copaxone (glatiramer acetate) Treatment to Reduce Frequency of Relapses in Relapsing-Remitting Multiple Sclerosis Professional Exhibit Panel at American Academy of Neurology Conference

23. Copaxone: Overstatement of Efficacy Claim: “20 years of proven safety.” FDA Comments About Exhibit Panel: Long term… safety and efficacy… has not been demonstrated by substantial evidence or substantial clinical experience. The CLINICAL STUDIES section of the PI only includes data for up to three years in duration. Long term… safety and efficacy… has not been demonstrated by substantial evidence or substantial clinical experience. The CLINICAL STUDIES section of the PI only includes data for up to three years in duration.

25. Copaxone: Omission of Information Claim: “Copaxone is NOT associated with immunosuppression/serious infections, decrease in pulmonary function, or anaphylaxis.” FDA Comments About Exhibit Panel: The table suggests that Copaxone is not associated with immunosuppression/infections, pulmonary function, and anaphylaxis/hypersensitivity, when this is not the case. The table suggests that Copaxone is not associated with immunosuppression/infections, pulmonary function, and anaphylaxis/hypersensitivity, when this is not the case. The table fails to present the Warnings for chest pain, skin necrosis and… effects… on immune response. The table fails to present the Warnings for chest pain, skin necrosis and… effects… on immune response.

26. “Running, Swimming, and Biking Against MS” “Taking on MS, One Step at a Time”

27. Copaxone: Broadening of Indication FDA Comments About Exhibit Panel: Copaxone is indicated for [relapse-remitting multiple sclerosis]. Copaxone is indicated for reduction of the frequency of relapses in patients with RRMS [relapse-remitting multiple sclerosis]. However… the webpages make claims that misleadingly broaden the indication for Copaxone, such as, “ ”… and “." However… the webpages make claims that misleadingly broaden the indication for Copaxone, such as, “Running, Swimming and Biking Against Multiple Sclerosis”… and “Taking on Multiple Sclerosis, One Step at a Time."

28. Angiomax (bivalirudin) Angiomax (bivalirudin) Anticoagulant Professional Booth Panel

29. Angiomax: Omission of Risk Information FDA Comments About Booth Panel: The booth panel fails to convey that the most common adverse event associated with Angiomax was bleeding, which was experienced in 28% of patients. The booth panel fails to convey that the most common adverse event associated with Angiomax was bleeding, which was experienced in 28% of patients.

30. References

31. Angiomax: Unsubstantiated Superiority Claims in References FDA Comments About Booth Panel: “The Rich, et al. 2 study does not constitute substantial evidence to support claims and presentations implying that Angiomax is clinically superior to heparin ‘throughout the risk spectrum.’” “The Rich, et al. 2 study does not constitute substantial evidence to support claims and presentations implying that Angiomax is clinically superior to heparin ‘throughout the risk spectrum.’” The Acuity PCI study failed to show non-inferiority of Angiomax to enoxaparin or UFH when analyzed for the endpoint of death or MI at 30 days. The Acuity PCI study failed to show non-inferiority of Angiomax to enoxaparin or UFH when analyzed for the endpoint of death or MI at 30 days.

32. FDA's "Bad Ad" Program Launched in 2010Launched in 2010 Designed to educate healthcare providers about the role they can play in helping make sure that prescription drug advertising is truthfulDesigned to educate healthcare providers about the role they can play in helping make sure that prescription drug advertising is truthful Provides an easy way to report misleading information to the agency:Provides an easy way to report misleading information to the agency: E-mail or call 855-RX-BADAD. E-mail BadAd@fda.gov or call 855-RX-BADAD. To learn more, go to To learn more, go to Fda.gov/badad.

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