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Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished trials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 Empty boxes show published studies and filled boxes show unpublished studies.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