Evaluating Psychopharmaceuticals: Lessons from a Skeptic

Transcription

1 Evaluating Psychopharmaceuticals: Lessons from a Skeptic Daniel Carlat, M.D Division 55 Midwinter Conference

2 Disclosures Associate Clinical Professor, Tufts School of Medicine Publisher, The Carlat Psychiatry Report ( No pharmaceutical industry funding (since 2002)

3 Vilazodone

4 Oleptro

5 Silenor

6 Objectives 1. Understand the basics of deceptive pharmaceutical marketing 2. Recognize the manipulation of scientific data

7 Deceptive Marketing Deceptive promotional activities (to be covered) Deceptive accredited educational activities (commercial CME or CE) (too vast to cover today)

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9 The Motto "A lie gets halfway around the world before the truth has a chance to get its pants on." - Sir Winston Churchill ( )

10 Effexor XR Boot Camp New York Times Magazine, November 25, 2007

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16 Thase ME, et al. Br J Psychiatry. 2001;178: What about Response Rates?

17 7 Years Later The overall difference in ITT remission rates was 5.9% favoring venlafaxine (95% confidence interval [CI]: ; p <.001). Based on this difference, the number needed to treat (NNT) to benefit is 17 (95% CI: 12 26). Nemeroff et al., Biol Psychiatry 2008 Feb 15;63(4): Epub 2007 Sep 24.

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19 Lunch and Learns

20 Prescription Data Mining

21 Prescription Data-Mining Local pharmacies sell information Data-mining companies buy names from AMA Real time prescribing information for pharm reps

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23 Data-Mining in Action Our main target, Dr. Schiavoni, is an internist. He spreads his usage among 3 antidepressants, Celexa, Zoloft and Paxil at about percent each. He is currently using about 6% Effexor XR. Our access is very challenging and lunches 6 months out. Fax to Dr. Carlat from Wyeth rep, 5/24/02

24 More Data-Mining Dr. Curtis is a Decile 6 doctor and is not prescribing any Effexor XR, so please tailor accordingly. Fax to Dr. Carlat from Wyeth rep, 8/15/02

25 Drug Rep Jargon High-Writers Low-Writers No-Sees The Spreader The Grower The Samplegrabber

26 The Bottom Line It s my job to figure out what a physician s price is. For some it s dinner at the fi nest restaurants, for others it s enough convincing data to let them prescribe confidently and for others it s my attention and friendship...but at the most basic level, everything is for sale and everything is an exchange. Shahram Ahari, former Eli Lilly rep

27 Why Doctors Do It

28 Manipulating the Science 1. Tweaking study design 2. Burying inconvenient data

29 Starting a Newsletter

30 Ragging on Cymbalta

31 LOCF vs. MMRM

32 Eli Lilly Attorney Attacks

33 A Novel Antidepressant

34 Pristiq is Here!

35 Wyeth Press Release A structurally novel serotoninnorepinephrine reuptake inhibitor (SNRI) a once-daily 50-mg dose that does not require titration, allowing physicians to start their patients at the recommended therapeutic dose.

36 Press Release, Para #7 PRISTIQ delivers the major active metabolite of EFFEXOR XR (venlafaxine HCl) in its active state without going through the CYP2D6 metabolic pathway.

37 Unveiling Deceptive Information: Three Key Questions Who is the Sponsor? Compared to What? Where is the (hidden) Data?

38 Who is the Sponsor? WYETH

39 Compared to What? Pristiq vs. Placebo Pristiq 11.5 pt. improvement on Ham- D Scale; Placebo: 9.5 pt. improvement Total possible points: 52

40 Pristiq vs. Effexor Pristiq 50 mg vs. Effexor 75 mg no data Difference between Pristiq 50 mg and Placebo: pts. Difference between Effexor 75 mg and Placebo: 3-5 pts.

41 How is Wyeth being Deceptive? 1. Not really novel 2. No real dosing advantage

42 Even the Wyeth Reps are Skeptical PRISTIQ - Good luck selling both Effexor XR and Pristiq at the same time. So Dr., would you like to hear about my antidepressant that has been around for 12 years, with proven efficacy with the ability to titrate the dose as need to better care for each patient's needs that will have generic competition in 4 months, or would you like to hear about my brand new antidepressant with one dose, less indications and less evidence of efficacy? You want me to choose, let me check with my bonus plan to see which one pays more. From Café Pharma Website, 3/3/08

43 My most Popular Blog Post

44 How has Pristiq Done?

45 Vilazodone

46 Press Release A new molecular entity and the first and only selective serotonin reuptake inhibitor and 5HT1A receptor partial agonist.

47 Is it Effective?

48 No Sexual Side Effects?

49 Not Really Placebo and vilazodone patients began with sexual dysfunction 8 weeks later, they still had sexual dysfunction Ceiling effect

50 The FDA is skeptical "The FDA does not agree with the claim about sexual side effects," explains Walsh [Sandy Walsh, FDA spokesperson]. "There is not sufficient data for that claim. The drug company did use some sexual function assessments in some of its trials, and the results were mixed." AOL Health News, Jan 27, 2011

51 Oleptro (trazodone extended-release)

52 Oleptro s One Study One published study, n = mg vs. placebo Oleptro improved HamD 2 points more than placebo Sheehan DV et al, Psychiatry (Edgmont) 2009;6(5):20 33

53 Oleptro makes you dizzy and tired

54 But there s always a way to spin Sheehan DV et al, Psychiatry (Edgmont) 2009;6(5):20 33

55 Silenor (doxepin)

56 Silenor s Efficacy Superior to placebo for sleep maintenance, not initiation FDA indication for 3 mg and 6 mg dosages

57 Silenor vs. doxepin Same molecule Silenor comes in 3 mg and 6 mg; doxepin s lowest strength is 10 mg One month supply Silenor $214 Doxepin $4 (Walmart)

58 Informed Skepticism Is the new drug evergreened? Have the right studies been done? Has the research design been manipulated? What are the cost implications?

59 Reasons for Hope Physician Payment Sunshine Act Propublica.org Clinicaltrials.gov American Psychiatric Association ending industry funded symposia

60 Doctors are Getting the Message

61 The Brain is Complicated