Spontaneous Publishing and Academic Miscarriages (SPAM)
In 1991 in the
week FDA held regulatory hearings on Prozac and suicide, the BMJ published
an article by Lilly employees exonerating Prozac of blame even though
there was a clear increase in risk on treatment in the published article
and the article included under the heading of placebo a suicide that had
not happened in the randomized phase of the trials (1)(2). This likely
played a part in the way academics worldwide viewed the issues. Since
then in my experience in the run up to major legal trials or regulatory
hearings linked to SSRIs, one or other major journal has run an article
exonerating the drug(s). (I have no idea if something similar can be
linked to legal or regulatory issues involving other pharmaceuticals such
as Vioxx).
This week’s BMJ has an article on birth defects and SSRIs which
points to a risk on treatment (3). It is accompanied by an editorial
minimising those risks by Dr Chambers who has co-authored other pieces
advocating the treatment of antenatal depression with antidepressants (4).
Intriguingly Dr Chambers is in possession of a dataset pointing to
statistically significant 5.1 fold increased odds ratio of major birth
defects and a 10.8 fold increased odds ratio of cardiac defects on Paxil
but these data remain unpublished in the peer-reviewed literature almost
10 years after they were first generated (5).
This week GlaxoSmithKline open their defence in the first Paxil
linked birth defect case to go to trial. What odds their lead counsel
will brandish a copy of the BMJ in front of jurors? I have no reason to
think any member of the editorial staff of BMJ have been complicit in any
wrongdoing but there does seem to be something here worthy of further
investigation. Dr Chambers’ argument is that the risks of non-treatment
outweigh the risks of treatment – despite a doubling of the risk of
miscarriage. But do the risks of publication of this editorial outweigh
the risks of non-publication? Is there in other words a need for some SPAM
filter here?
References
1. Healy D. Did regulators fail over selective serotonin reuptake inhibitors?
BMJ Jul 2006; 333: 92 - 95.
2. Beasley CM, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH, Heiligenstein JH. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ 1991;303: 685-92.
3. Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH.
Selective serotonin reupake inhibitors in pregnancy and congenital
malformations: population based cohort study. BMJ 2009;339:b3569
doi:10.1136/bmj.b.3569
4. Chambers C. Selective serotonin reuptake inhibitors and
congenital malformations. The small risk of harm must be balanced against
risk of suboptimal or no treatment. BMJ 2009; 339: b3525
doi:10.1136/bmj.b3525.
Competing interests:
DH is a witness for the plaintiff in the legal case mentioned in this letter. In the past 10 years DH has had consultancies with, been a principal investigator or clinical trialist for, been a chairman or speaker at international symposia for or been in receipt of support to attend meetings from: Astra-Zeneca, Boots/Knoll Pharmaceuticals, Eli Lilly, Janssen-Cilag, Lorex- Synthelabo, Lundbeck, Organon, Pharmacia & Upjohn, Pierre- Fabre, Pfizer, Rhone-Poulenc, Roche, Sanofi, GlaxoSmithKline, Solvay In the past two years, DH has had lecture fees and support to attend meetings from Astra- Zeneca and Lundbeck. In the past ten years DH has been an expert witness for the plaintiff in 15 legal actions involving SSRIs and has been consulted on a number of attempted suicide, suicide and suicide-homicide cases following antidepressant medication, in most of which he has offered the view that the treatment was not involved. He has also been an expert witness in one patent case, and one securities case.
Competing interests:
No competing interests
01 October 2009
David Healy
Professor
Department of Psychiatry, Cardiff University, United Kingdom
Rapid Response:
Spontaneous Publishing and Academic Miscarriages (SPAM)
In 1991 in the
week FDA held regulatory hearings on Prozac and suicide, the BMJ published
an article by Lilly employees exonerating Prozac of blame even though
there was a clear increase in risk on treatment in the published article
and the article included under the heading of placebo a suicide that had
not happened in the randomized phase of the trials (1)(2). This likely
played a part in the way academics worldwide viewed the issues. Since
then in my experience in the run up to major legal trials or regulatory
hearings linked to SSRIs, one or other major journal has run an article
exonerating the drug(s). (I have no idea if something similar can be
linked to legal or regulatory issues involving other pharmaceuticals such
as Vioxx).
This week’s BMJ has an article on birth defects and SSRIs which
points to a risk on treatment (3). It is accompanied by an editorial
minimising those risks by Dr Chambers who has co-authored other pieces
advocating the treatment of antenatal depression with antidepressants (4).
Intriguingly Dr Chambers is in possession of a dataset pointing to
statistically significant 5.1 fold increased odds ratio of major birth
defects and a 10.8 fold increased odds ratio of cardiac defects on Paxil
but these data remain unpublished in the peer-reviewed literature almost
10 years after they were first generated (5).
This week GlaxoSmithKline open their defence in the first Paxil
linked birth defect case to go to trial. What odds their lead counsel
will brandish a copy of the BMJ in front of jurors? I have no reason to
think any member of the editorial staff of BMJ have been complicit in any
wrongdoing but there does seem to be something here worthy of further
investigation. Dr Chambers’ argument is that the risks of non-treatment
outweigh the risks of treatment – despite a doubling of the risk of
miscarriage. But do the risks of publication of this editorial outweigh
the risks of non-publication? Is there in other words a need for some SPAM
filter here?
References
1. Healy D. Did regulators fail over selective serotonin reuptake inhibitors?
BMJ Jul 2006; 333: 92 - 95.
2. Beasley CM, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH, Heiligenstein JH. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. BMJ 1991;303: 685-92.
3. Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH.
Selective serotonin reupake inhibitors in pregnancy and congenital
malformations: population based cohort study. BMJ 2009;339:b3569
doi:10.1136/bmj.b.3569
4. Chambers C. Selective serotonin reuptake inhibitors and
congenital malformations. The small risk of harm must be balanced against
risk of suboptimal or no treatment. BMJ 2009; 339: b3525
doi:10.1136/bmj.b3525.
5. www.gsk-clinicalstudyregister.com/files/pdf/24089.pdf
Competing interests:
DH is a witness for the plaintiff in the legal case mentioned in this letter. In the past 10 years DH has had consultancies with, been a principal investigator or clinical trialist for, been a chairman or speaker at international symposia for or been in receipt of support to attend meetings from: Astra-Zeneca, Boots/Knoll Pharmaceuticals, Eli Lilly, Janssen-Cilag, Lorex- Synthelabo, Lundbeck, Organon, Pharmacia & Upjohn, Pierre- Fabre, Pfizer, Rhone-Poulenc, Roche, Sanofi, GlaxoSmithKline, Solvay In the past two years, DH has had lecture fees and support to attend meetings from Astra- Zeneca and Lundbeck. In the past ten years DH has been an expert witness for the plaintiff in 15 legal actions involving SSRIs and has been consulted on a number of attempted suicide, suicide and suicide-homicide cases following antidepressant medication, in most of which he has offered the view that the treatment was not involved. He has also been an expert witness in one patent case, and one securities case.
Competing interests: No competing interests