How are (flemish) psychiatrists being influenced by the pharmaceutical industry?Manuel Morrens

Disclosure of conflict of interests in the last 5 years

Fee or other payment for lectures given

AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Sandoz

Scientific Boards Janssen-Cilag Belgium

Sponsorship for congress None

Research funding Johnson & Johnson Belgium, Lundbeck Belgium

How are psychiatrists influenced by the pharmaceutical industry?

How are we influenced?

Confounders in scientific literature

Influencing the prescribing doctor

Flemish prescription patterns: the case of antipsychotics

Conclusions

How are psychiatrists influenced by the pharmaceutical industry?

How are we influenced?

Confounders in scientific literature

Influencing the prescribing doctor

Flemish prescription patterns: the case of antipsychotics

Conclusions

What sources of Information

Basic medical training

Scientific literature

Extra training: Symposia, conferences,…

Contacts with drug reps

…

How many clinical research is industry funded?

Anderson et al., NEJM, 2015

Industry Trials

NIH Trials

Other trials (academic or government)

0 1500 3000 4500 6000

Phase 1-2Phase 2-3Phase 4

Source= clinicaltrials.gov (until 9/2013)

Impact of the sponsor of the study on efficacy results

Impact of sponsor of the trial on outcome of psychiatric drug studies

0

20

40

60

80

Industry supported Studies

Independently funded trials

ISS-competitor drug

Kelly et al., 2006N= 542 publications (1992, 2002)

Percentage of Favorable outcome reports according to trial sponsor

Heres et al., Am J Psychiatry, 2006

Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished trials

Forest plot showing meta-analyses of remission and response rates for trials that compared reboxetine with placebo. Empty boxes show published studies and filled boxes show unpublished studies.

Melander et al., BMJ, 2003Drugs: 5 SSRI’s (Studies n=42) Impact analysis: protocol finishers vs ITT

What about clinicaltrials.gov?2000: creation of clinicaltrials.gov

information about and access to clinical trials

In 2007:FDA requires sponsors to register and report basic summary results at clinicaltrials.gov

FDA also mandates that trial results be reported by the sponsor within 1 year after the completion of data collection

Anderson et al, 2015

Reasons given by investigators for not publishing

Song et al., 2010

International Committee of Medical Journal Editors (ICMJE)

0

12,5

25

37,5

50

Adequ

ately

registe

red Lacki

ng

registr

ation

Registr

ation a

fter

study

comple

tion

Flawed

registr

ation

N=323

2008

Mathieu et al., 2009

%

Are psychiatrists influenced by the pharmaceutical industry?

How are we influenced?

Confounders in scientific literature

Influencing the prescribing doctor

Flemish prescription patterns: the case of antipsychotics

Conclusions

Influencing the prescribing doctor

Opinion leaders in the media

Impact of pharma representatives visits

Pharmaceutical industry spent 57.5 billion dollars on pharmaceutical promotion in US in 2004

(1)

Impact of contacts with Pharma sales representatives or sponsored meeting (1,2)

Increased prescription rates of sponsored drug

Lower adherence to guidelines and recommendations

higher prescribing cost

(1) Spurling et al, 2010 (2) Spingarn et al., 1996

Reps actively selected for outgoing nature, befriending style

Assessing the physician’s personalities

‘Physician category’

Technique per category how to convince to prescribe

Personal information is asked for (and put in database)

Skeptical doctors are wooed as teachers

Prescription tracking (IMS health buys records from pharmacies)

Identifying physicians susceptible for marketing

Seeding trialsTrials sponsored by sales and marketing department rather than R&D division

‘Investigators’ chosen not for their expertise, but because they prescribe competitor’s drug

Especially opinion leaders

Multiple inclusion sites (sometimes >100)

Study design is poor

But things are (somewhat) changing..Golden era is over, products are getting off patent

Increasing awareness

Conferences & symposia no longer sponsored (APA,…)

Fewer/no more gifts

Pharmaceutical industry also making effort to more balanced interaction:

www.pharma.be

betransparent.be

Decline in reps, focus on ‘key figures’:

Teachers, speakers, admission unit psychiatrists

Rise of digital tools

Apps

Infogaming

e-learning

Are psychiatrists influenced by the pharmaceutical industry?

How are we influenced?

Confounders in scientific literature

Influencing the prescribing doctor

Flemish prescription patterns: the case of antipsychotics

Conclusions

StellingenTweede generatie zijn beter dan eerste generatie antipsychotica tegen positieve symptomen

Tweede generatie zijn beter dan eerste generatie antipsychotica tegen negatieve symptomen

Tweede generatie zijn beter dan eerste generatie antipsychotica tegen cognitieve symptomen

Tweede generatie antipsychotica hebben een gunstiger nevenwerkingsprofiel?

Are SGA truly more effective?

Leucht et al., Lancet, 2008

Antipsychotics in Adults With Schizophrenia: Comparative Effectiveness of First-Generation Versus Second-Generation Medications: A Systematic Review and Meta-analysis

Hartling, Ann Int Med, 2010

Do SGA have superior effects on cognitive symptoms: What do meta-analyses say?

-0,25

0

0,25

0,5

0,75

1

Attention Automatic ProcessingExecutive Functioning General IntellectLanguage MemoryMotor Functioning Perceptual Processing

0

0,25

0,5

0,75

1

Immediate memory Secondary memoryAttention Executive FunctioningVisuomotor Functioning Verbal FluencySpatial memory

Second Generation AntipsychoticsFirst Generation Antipsychotics

Mishara & Goldberg, 2004 Harvey & Keefe, 2001

Cognitive effects of antipsychotics vs other agents

Antipsychotics (Keefe et al,

2007)

d-cycloserine (Buchanan et al,

2007)

Glycine (Buchanan et al,

2007)

galantamine (Buchanan et al,

2008)

Practice effect (Goldberg et al,

2007)

Effe

ct S

ize (C

ohen

’s d)

Evolution of prescription rates SGA and FGA in Belgium

050

0000

01000

0000

1500

0000

2000

0000

1998 2000 2002 2004 2006 2008 2010 2012

GP-FGA GP-SGAPSY/NEUR-FGA PSY/NEUR-SGA

Morrens et al., J Psychiatr Practice, 2015

Prescription rates in Belgium

0

1000

000

2000

000

3000

000

4000

000

1997 1999 2001 2003 2005 2007 2009 2011

RisperidoneClozapineOlanzapineAmisulprideQuetiapineAripiprazoleSertindolePaliperidoneAsenapineHaloperidolBromperidolZuclopenthixolFlupentixolPimozideProthipendylThioridazineSulpirideDroperidolPipamperonLevomepromazineClotiapineOther FGAOther FGA

Morrens et al., J Psychiatr Practice, 2015

Prescription Ratio between MD age categories

0

0,175

0,35

0,525

0,7

20-35 36-50 51-65 66-80 80+

1st gen AP 2nd gen AP

Morrens et al., J Psychiatr Practice, 2015

Are  Belgian  doctors  in0luenced  by  the    

pharmaceutical  industry  when  prescribing  antipsychotics?

Survey July 2014 - December 2014

VVP, Domus Medica, Huisartsenbringen, Vereniging van wijkgezonheidscentra, Geneeskunde voor het Volk, alle CGGZ’s, alle PZ en PAAZ afdelingen.

Response Rate:

Psychiatrists n=101 (total of 600 psychiatrists in 2015)

General Practicioners n=54 (total of 8181 GPs in 2013)

Cleymans, Bervoets & Morrens, subm

Do you meet with reps?

No 20%

Yes 80%

Psychiatrists 45% GPs

55%

Which medical firms do you see most often?

0

10,5

21

31,5

42

AstraZeneca Eli-Lilly Janssen Lundbeck

Do you think you are influenced?

No 59%

Yes 41%

Years of experience?

>30y

11-30y6-10y

< 5y

Are Belgian doctors influenced by the pharmaceutical industry when prescribing antipsychotics?

Cleymans, Bervoets, Morrens, Subm

Top three products of choice in Flemish psychiatrists and GPsAmisulpride (Solian)

Aripiprazol (Abilify)Bromperidol (Impromen)

Clotiapine (Etumine)Clozapine (Leponex)

Droperidol (Dehydrobenzperidol)Flupentixol (Fluanxol)

Fluspirileen (Imap)Haloperidol (Haldol)

Levomepromazine (Nozinan)Olanzapine (Zyprexa)

Paliperidon (Invega)Pimozide (Orap)

Pipamperon (Dipiperon)Prothipendyl (Dominal)Quetiapine (Seroquel)Risperidon (Risperdal)

Sertindol (Serdolect)Sulpiride (Dogmatil)

0% 22,5% 45% 67,5% 90%

GPsPsychiatrists

Cleymans, Bervoets, Morrens, Subm

Assumptions on efficacy of SGA

Percentage of repondents that think SGA are superior to FGA concerning …

Positive symptoms

Negative symptoms

Cognitive symptoms

Side effect profile

0,2 0,4 0,6 0,8

71,6%

59,4%

66,4%

33%

Cleymans, Bervoets, Morrens, Subm

Rho = .478***

Rho = .401***

Rho = .291***

Influence of sponsoring

sponsoring (Sponsored lectures,

diners, conference attendance)

Positive attitude towards the

industry

Positive assumptions on

SGA (especially cogn symptoms)

rho = 0.236 ** rho = 0.226 **

rho = 0.406 *** rho = 0.549 ***

All respondents

Respondents denying influenceCleymans, Bervoets, Morrens, Subm

Time spent with representative

(especially in young

colleagues)

Transparantie van Belgische Psychiaters

Are psychiatrists influenced by the pharmaceutical industry?

What’s at stake?:Drug Development & Pharmaceutical Industry

How are we influenced?

Confounders in scientific literature

Influencing the prescribing doctor

Flemish prescription patterns: the case of antipsychotics

Conclusions

Conclusions