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Do drug companies help or hurt patients? Gilbert Chu, MD, PhD Professor of Medicine and Biochemistry Down to a Science Cafe December 2007 Gilbert Chu,

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Presentation on theme: "Do drug companies help or hurt patients? Gilbert Chu, MD, PhD Professor of Medicine and Biochemistry Down to a Science Cafe December 2007 Gilbert Chu,"— Presentation transcript:

1 Do drug companies help or hurt patients? Gilbert Chu, MD, PhD Professor of Medicine and Biochemistry Down to a Science Cafe December 2007 Gilbert Chu, MD, PhD Professor of Medicine and Biochemistry Down to a Science Cafe December 2007

2 New drugs for cancer patients Targeted attack of tumors Gleevec kinase inhibitor for chronic myeloid leukemia (Novartis) Avastin antibody vs. vascular endothelial growth factor (Genentech) Control of chemotherapy side effects Epogen red cell growth factor (Amgen) Neulasta neutrophil growth factor (Amgen)

3 Laws affect Pharma behavior 1980Bayh-Dole Act Permits pharma to license NIH-funded research

4 1980Bayh-Dole Act Permits pharma to license NIH-funded research 1984Hatch-Waxman Act Exempts generic companies from repeating clinical trials; delays approval by 30 months if brand-name company sues to protect patents 1992Prescription Drug User Fee Act (PDUFA) Charges $576,000 for each FDA application 1997FDA guidelines on TV ads 2003Medicare prescription drug benefit Prohibits Medicare from negotiating lower prices Laws affect Pharma behavior

5 How much money is involved? Colon cancer treatment SurvivalCost 8 wks FL (fluorouracil, leucovorin)12 mo$63 FL, Eloxatin21 mo$12,000 FL, Eloxatin, Avastin27 mo$21,000 Aventis: Eloxatin Genentech: Avastin

6 SLAC budget $150 M How much money is involved? Net profits (Fortune 500) 10 pharma companies$36 B 490 non-pharma companies$34 B CEO salaries plus stock options Bristol-Myers Squibb$151 M Wyeth$82 M

7 How much money is involved? Net profits (Fortune 500) 10 pharma companies$36 B 490 non-pharma companies$34 B CEO salaries plus stock options Bristol-Myers Squibb$151 M Wyeth$82 M Expenses vs. profits Marketing35% Research (mostly clinical trials)11% Profits20%

8 African black fly microfilaria river blindness elephantiasis Merck as a pharmaceutical leader

9 : Roy Vagelos - Chairman/CEO Americas most admired corporation for 7 yrs 1987: ivermectin - anti-parasitic drug Used for heartworm in dogs Found to cure river blindness, then elephantiasis Merck donated drug to patients without charge 1994: Ray Gilmartin takes over…

10 Dorothy Hamill The Vioxx case

11 Cyclo-oxygenase (COX) enzymes prostaglandins in inflammatory cells contribute to: pain heat swelling housekeeping substances in: platelets (to make blood clots) stomach mucosal cells (for stomach protection)

12 Aspirin or Naprosyn X X Cyclo-oxygenase (COX) enzymes prostaglandins in inflammatory cells contribute to: pain heat swelling housekeeping substances in: platelets (to make blood clots) stomach mucosal cells (for stomach protection)

13 Vioxx X Cyclo-oxygenase (COX) enzymes Annual sales: $3.5 billion prostaglandins in inflammatory cells contribute to: pain heat swelling housekeeping substances in: platelets (to make blood clots) stomach mucosal cells (for stomach protection)

14 blood vessel endothelial cells (to prevent clots) Cyclo-oxygenase (COX) enzymes housekeeping substances in: platelets (to make blood clots) stomach mucosal cells (for stomach protection) prostaglandins in inflammatory cells contribute to: pain heat swelling

15 blood vessel endothelial cells (to prevent clots) Vioxx X Cyclo-oxygenase (COX) enzymes Could Vioxx cause heart attacks? housekeeping substances in: platelets (to make blood clots) stomach mucosal cells (for stomach protection) prostaglandins in inflammatory cells contribute to: pain heat swelling

16 Matthew & Martinez. s suggest that Merck knew Vioxxs dangers at early stage. Wall Street Journal, Nov. 1, 2004 The Vioxx case 1997: Alise Reicin, V.P. Clinical Research, Merck studies should be designed so risks would not be evident

17 The Vioxx case Matthew & Martinez. s suggest that Merck knew Vioxxs dangers at early stage. Wall Street Journal, Nov. 1, 2004 Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ; VIGOR Study Group Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis New England Journal of Medicine, November : Alise Reicin, V.P. Clinical Research, Merck studies should be designed so risks would not be evident

18 1997: Alise Reicin, V.P. Clinical Research, Merck studies should be designed so risks would not be evident Merck: 16 pages of instructions, Dodge Ball Vioxx responses to physician queries were labeled as: DODGE! Gurkirpal Singh, Asst. Prof. speaker sponsored by Merck criticism of missing safety data led Merck to threaten Stanford The Vioxx case Matthew & Martinez. s suggest that Merck knew Vioxxs dangers at early stage. Wall Street Journal, Nov. 1, 2004

19 Richard Horton, Editor and Publisher, The Lancet In a recent Editorial, we commended Merck for acting promptly in the face of new findings about the safety of Vioxx... Our praise was premature... Merck and the FDA acted out of ruthless, short- sighted, and irresponsible self-interest. The Vioxx case

20 Clinical trials showed increased risk of heart attacks for Vioxx when compared to naprosyn The Vioxx case A crash course on statistics… p-value is the probability that the result could have occurred by chance Physicians consider a result meaningful if p<0.05 Example: in a study of 1000 patients comparing Drug X to Drug Y, heart attacks occurred in 8 patients on X, 3 patients on Y 8 patients on X, 1 patient on Y p=0.22 p=0.04

21 Clinical trials showed increased risk of heart attacks for Vioxx when compared to naprosyn 16 randomized trials, Relative riskp value All 16 trials 2.24 Trial duration 6 months < 6 months 2.33 Independent endpoint committee? Yes (8 trials) No or unclear (8 trials) 0.79 The Vioxx case Bombardier et al. suggested that the difference might be due to a protective effect of naprosyn

22 sponsored by Merck p = Favors naproxenFavors control Combined 0.86 (95% CI ) Clinical trials failed to show protection from naproxen The Vioxx case

23 Lisse JR et al. for the ADVANTAGE Study Group Gastrointestinal tolerability and effectiveness of rofecoxib versus naproxen in the treatment of osteoarthritis; a randomized controlled trial Annals Internal Med, October 2003

24 The Vioxx case Lisse et al. reported heart attacks in 5 patients on Vioxx compared to 1 patient on naproxen, p = 0.22 Data originally filed at FDA documented heart attacks in 8 patients on Vioxx compared to 1 on naproxen, p = 0.04 Dr. Alise Reicin asked for new diagnoses: I would prefer unknown cause of death so we dont raise concerns Dr. Jeffrey Lisse (U. Arizona) claimed to be unaware of the altered diagnoses: Merck designed the trial, paid for the trial, ran the trial…The initial paper was written at Merck and then sent to me for editing Alex Berenson, Evidence in Vioxx suits shows intervention by Merck officials. New York Times, Apr 24, 2005

25 The Vioxx case Deaths attributable to Vioxx50,000 American deaths in Vietnam58,000 American deaths in Iraq (12/1) 3,882

26 The Vioxx case Merck officials altered the data designed the trials to conceal risks Academics physicians authored key papers delivered continuing medical education FDA failed to monitor the safety of Vioxx Where were the problems?

27 Is the medical literature biased? Ghost writers in research papers (Flanagin et al. JAMA 1998) Annals of Internal Medicine (20%) New England Journal of Medicine (26%) Randomized myeloma trials favoring new drug (Djulbegovic et al. Lancet 2004) When NOT sponsored by industry: 47% (p =.608) When sponsored by industry: 74% (p =.004)

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29 Can we fix the problem? Financial disclosure ClinicalTrials.gov Ban of pharma reps Unbiased drug trials

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