Dr. David Healy Addresses Credibility Crisis-at Columbia University Oct. 20

Additional information as of late Wed Oct 19:

Although I was assured that attendance for a presentation by Dr. David Healy (at Columbia University School of Public Health on Oct. 20 at 12:30) would be open to the public, a problem seems to have emerged after an AHRP Infomail about the presentation prompted many people to want to attend: Professor Sharon Schwartz, Professor, Department of Epidemiology at Columbia indicated: “many people have been conctacting us about it.”

Dr. Healy’s talk will focus on the latest data on SSRIs and suicide; company behavior in relation to this issue; and he will field questions on the role of conflicts of interest in this area.

I received the following notes today indicating the curtailment of attendees from the public. The note from Dr. Allan Horwitz (Professor of Sociology, Rutgers) states:

Unfortunately, rooms for speakers are at a great premium at Columbia and we havn’t been able to get larger room than one we originally scheduled the talk in, which holds > about 50 people. We expect that about 40 people will be attending from the > students and faculty of the Rutgers and Columbia programs. Therefore, if > more than 10 or so other people come, we won’t be able to accommodate them.

The note from Dr. Sharon Schwartz states:

[The presentation] < the room in which the event is taking place was meant for our two programs and is therefore too small to accommodate the public. Because of this situation, only people on a designated list will be allowed past security at the hospital.

You are welcome to come and we will put your name on the list so you should have no problem. If you want to bring a colleague, please let me know as soon as possible so that I can put him/her on the list as well and they can gain access.>

From these directives, it would appear that only 10 people who are not affiliated with Columbia or Rutgers faculty and students may get in if they call and gain a place on the list.

To be placed on the list, it is suggested that you contact:

Dr. Sharon Schwartz at: 212-305-7789– sbs5@columbia.edu ; Dr. Allan Horwitz: avhorw@rci.rutgers.edu

One would have hoped that public interest (by members of the wider academic and public health analyst community) in a presentation dealing with drug safety and medical ethics would be welcomed at institutions that receive very generous public support .

Contact: Vera Hassner Sharav
212-595-8974

Dr. David Healy Addresses Credibility Crisis-at Columbia University Oct. 20

Mon, 17 Oct 2005

“Psychopharmacology in Turmoil:A Scientific or Ethical Crisis?”
A lecture by Dr. David Healy will be presented within the framework of a joint program at Rutgers University and Columbia University, School of Public Health.

Date: Thursday, October 20 —Time: 12:30 – 2:00
Location: Columbia Presbyterian Hospital –622 West 168th Street
10th floor – Irving Conference Room
The lecture is open to the public–and there will be about 40 minutes for Q & A.
Directions (below)

The focus of Dr. David Healy’s presentation is the current credibility crisis in psychiatry: “I think the key issue here is the fact that ghostwriting has eviscerated the scientific literature in psychiatry.”

Background: Among recent FDA debacles that have shaken public trust in the FDA, in the safety of drugs and in the impartiality of those who recommend particular drugs, are revelations about concealed safety hazards linked to SSRI antidepressants.The concealed facts about an increased suicide risk were brought to public attention–first in the UK, then the US–by Dr. David Healy, an international expert in psychopharmacology who had gained access to secret company data documenting evidence of a twofold increased risk of suicidal acts by children and adolescents prescribed an antidepressant such as Zoloft, Paxil, or Prozac in clinical trials of short duration.

The current crisis is a result of the corrosive influence of the parmaceutical industry which has enlisted key opinion leaders in the profession: this collaborative effort expanded the market for psychotropic drugs while skewing the scientific process. Those who conduct clinical research can no longer be said to be impartial: clinical trial reports in the psychiatric literature are biased, incomplete, the data analysis is faulty, and trial findings have been manipulated to show a benefit while concealing the most severe adverse drug effects.  Dr. Healy will demonstrate how current clinical practice guidelines that purport to be “evidence-based” are not based on scientifically valid evidence at all.

His analysis of previously undisclosed company data from SSRI drug trials contradicted the published reports about these trials and his findings of a drug-induced suicide risk, challenged the mindset and prescribing practices of the psychiatric establishment in the UK, Canada, Australia, and the US. By bringing the undisclosed hazards to public notice, the debate about the efficacy and safety of SSRs–and the validity of the process by which they were tested–reached a crescendo.

In the UK the regulatory agency took incremental action (beginning June 2003) to discourage physicians from prescribing these drugs for children and adolescents.

Despite continued denial by the leadership of US academic psychiatry, the suicidal link to antidepressants is now a matter of public record.

After the Black Box label warnings (October 2004), the FDA issued an additional advisory to healthcare officials in July 2005, stating:

“FDA has concluded that suicidal thinking or behavior may increase in pediatric patients treated with any type of antidepressant, especially early in treatment. Increases in suicidal thinking or behavior due to drug can be expected in about 1 out of 50 treated pediatric patients. Note that, Zoloft is approved for treating pediatric patients only if they have obsessive-compulsive disorder.” http://www.fda.gov/cder/drug/InfoSheets/HCP/sertralineHCP.htm

On September 28, 2005, the UK issued practice guidelines effectively banning the use of atidepressant drugs for children. See: http://www.ahrp.org/infomail/05/09/28.php

The Practice guidelines issued for physicians in England and Wales were published by NICE (National Institute for Health and Clinical Excellence) and the National Collaborating Centre for Mental Health for the National Health Service.

The UK Guidelines–at: http://www.nice.org.uk/page.aspx?o=273073 provide guidance on identifying and managing depression in children and young people in primary, community and secondary care. The guidelines note: ³Advice on nutrition, exercise and sleep to help combat depression should be more readily available.²

Dr. Healy’s evidence-based challenge to drug regulators, manufacturers, and academic psychiatrists whose published reports were based on partial, positive data–has been met with ad hominem attacks that attempt to raise doubts about his character. But interestingly, none of his organized adversaries are prepared to debate him openly on the validity of the evidence.

Industry’s corrosive influence on academia has terrorized critics and stiffled debate about the value and hazards of psychotropic drugs. Psychiatry in particular has affected by this dangerous malaise. The most recent victim of a smear campaign aimed at ending the career of Dr. Gretchen LeFever, a critic of psychostimulant drugs for children loosely diagnosed with ADHD, has just been settled. Although Dr. LeFever won her protracted battle with Eastern Virginia Medical School, we ask: Why was she persecuted in the first place? See: http://bmj.bmjjournals.com/cgi/content/full/331/7521/865-a?ehom

The concerted campaign to smear Dr. Healy has included the FDA which provided Pfizer free use of its official government website to post Pfizer’s screed–a savage attack of Dr. Healy’s credibility, while denying the latter an opportunity to rebut. “Contra Pfizer,” published in the current journal, Ethical Human Psychiatry & Psychology, is Dr. Healy’s response to Pfizer’s letter (excerpt below).

A similar ad hominem attack directed at Healy’s character was hurled by Dr. James Coyne, chairman of psychiatry, University of Pennsylvania: “Lessons in Conflict of Interest: The Construction of the Martyrdom of David Healy and The Dilemma of Bioethics.” It was published in the American Journal of Bioethics (AJOB, which at the time was located at that university’s Center for Bioethics). The AJOB editors did not follow journal protocol for debate among academics–they failed to offer the subject of this attack an opportunity to respond. Indeed, the AJOB editors did not send a copy of the article to Dr. Healy.

The October 20 lecture was originally scheduled as a debate between Dr. Healy and Dr. Coyne who were invited by a joint program at Rutgers and Columbia University, School of Public Health. However, for reasons that are unclear, Dr. Coyne will not debate Dr. Healy but has asked that his article be distributed to the audience on Oct. 20. Dr. Coyne prefers to make his presentation –“Construction of the Martyrdom of David Healy and The Dilemma of Bioethics”–on October 25 at Rutgers.

In fairness to both presenters, it is hoped that the conference organizers will distribute copies of articles by each of the presenters to both audiences– at Columbia ( on October 20) and at Rutgers (on October 25).

Contact: Vera Hassner Sharav
212-595-8974

Directions to Columbia Presbyterian Hospital –622 West 168th Street
10th floor – Irving Conference Room
from Penn Station: take the #1 train (red line) uptown or the A train (blue line) uptown to 168th street.
At 168 Street station (#1 train) take the elevator up to 168th and Broadway
From A train: just go up the stairs to 168th and Broadway
From trains: walk west on 168th street 1/2 block to circular driveway: Presbyterian Hospital 622 west 168th street
get a pass from the guard. take elevator behind the guard desk to the 10th floor
go through the doors to the Irving Conference Room.

~~~~~~~~~~~~~~~~~

http://www.springerpub.com/journalsamples/contra_Pfizer.pdf

ETHICAL HUMAN PSYCHOLOGY & PSYCHIATRY: AN INTERNATIONAL JOURNAL OF CRITICAL INQUIRY
Volume 7, Number 3, Fall/Winter 2005
CONTRA PFIZER
By David Healy

In July 2004, Pfizer posted an ad hominem attack on me. on the Food and Drug Administration¹ (FDA) Web site under the heading of documents relevant to a then forthcoming Psychopharmacologic Drugs Advisory Committee (PDAC) hearing on the use of antidepressants in children (Ryder, 2004). FDA refused to post my response to the issues raised in the Pfizer document. This response has been adapted for a freestanding publication, and may be timely in light of the fact that the FDA has scheduled a further hearing on treatment-induced suicidality in adults for the fall of 2005. In completing this piece, I remain heavily constrained by confidentiality orders, and it can be noted that Pfizer has attempted to enforce such orders vigorously by means of court action.

Pfizer¹s letter starts with a commitment to open debate. The letter then seeks to attack my credibility in an ad hominem way rather than to address the scientific issues. This attack comes despite the fact that I have been previously invited by Pfizer to chair symposia for them, to author articles for journal supplements for them, to give international guest lectures for them, and to adjudicate on studies submitted for Pfizer research awards for them. Clearly, at one point Pfizer thought me a credible scientist in the area of psychopharmacology.”

More recently, however, when scientists from Pfizer have sought to have me come and speak at forums, they have been told by their superiors that this is not appropriate. Of even greater interest is that the senior Pfizer physician representing sertraline at the September hearings, Dr. C. Kremer, when working for another company had been a key person supportive of my involvement as an expert witness in court actions involving fluoxetine.

It has in fact been very difficult to get issues of suicidality and psychotropic drugs debated in academic forums. In one of the few such forums, at an Irish College of Psychiatrists meeting in 2003, my understanding is that many clinicians and academics in the audience were briefed by individuals linked to Pfizer and GlaxoSmithKline on issues to raise with Healy. Many of these issues are reproduced in this letter from Pfizer.

At other scientific meetings to which I have been invited to contribute on these issues, such as the International Society of Pharmacoepidemiology annual meeting, distinguished academics with links to some of the major companies producing selective serotonin reuptake inhibitors (SSRIs), who have never heard me present the data, it would appear, apparently sought to have me removed from the scientific program. Yet, when later given the chance to challenge the points I make, they have failed to ask me any questions in public.

I believe this effort to close down debate has little to do with the scientific issues, in that my work on these points has been extensively peer-reviewed and published in six different journals. I have taken the unusual step of presenting many of these reviews, especially the negative ones, on the Internet to make it clear where others differ in their interpretations of the data (Healy, 2004). I believe the issue has much more to do with my temerity in being prepared to testify as an expert for plaintiffs. Since my involvement as an expert witness, I have received documents from at least one public relations company working for one of the relevant SSRI companies that have listed me as a problem to be managed, and I think what we are witnessing here is part of the management strategy.

Before proceeding, it is worth putting the issue of expert witnessing in context. In over 90% of the SSRI cases on which I have been approached, I have given the view that the injuries in question have not been caused by the SSRI. I have charged nothing for the great majority of these reports, or nothing for any reports I have offered to coroners¹ courts for the purposes of inquests.

Moreover, regarding actions by plaintiffs in general, far from being plaintiff friendly, I have been used as an expert by the National Health Service in the United Kingdom, and in that capacity have offered reports favoring the defense rather than plaintiffs in, again, over 90% of cases.

It should also be noted that I have no interests in any competing treatments. I use antidepressants, including SSRIs, to treat both adults and children, and, as a former secretary of the British Association for Psychopharmacology, convened a consensus conference and authored the ensuing guidelines on the issue of treating children with psychotropic drugs (BAP, 1997). These guidelines endorsed the cautious use of such drugs, a position I maintain to this day.

SPECIFIC RESPONSES TO PFIZER

In its July 2004 letter to the FDA, Pfizer made 12 points to which I will respond.

First, the company claims its depression program has shown no evidence of suicidality. In fact, Pfizer¹s depression program has a roughly 50% failure to demonstrate efficacy in clinical trials, and many of the trials undertaken with Zoloft remain unpublished. So poor were the results from the early trials that they raised concerns that this drug might not get approved, as publicly available memoranda from Dr. P. Leber to Dr. R. Temple indicate (Leber, 1991a, 1991b).

Zoloft, however, on the back of a selected set of published-only studies, has been sold by Pfizer as an SSRI with unparalleled evidence of efficacy. Arguably, there is a comparable discrepancy between the claims made by Pfizer and the evidence base for those claims, and the claims made for the use of Paxil for minors and the evidence base for that use. The claims in the latter instance were characterized in June 2004 by the attorney general from New York, Elliot Spitzer, as close to fraudulent. Regarding the evidence for suicidality from the Zoloft studies, in over 20 cases investigators have concluded that Zoloft has caused suicidality/suicidal acts, and in more than 20 further cases, Pfizer monitors overrode the judgments of the clinical investigators who had not linked Zoloft to suicidality. These Pfizer personnel attributed causality to Zoloft in the cases of these suicidality/suicidal events. Given this, it is something of a mystery as to how Pfizer can claim there is no evidence their drug causes suicide.

When data from the studies undertaken and submitted to FDA are analyzed statistically, the point estimate for the odds ratio of suicidal acts on Zoloft compared to placebo is greater than 1.0, which is indicative of a risk, and probably greater than 2.0. Pfizer has sought to manage this problem by a variety of methods, detailed below. The question of what a point estimate greater than 1.0 means in the context of SSRIs and suicide raises issues of interpretation that epidemiologists and others interested in safety issues have to deal with. Many reputable figures in these areas, including some working in the FDA, would argue that the correct interpretation of a point estimate greater than 1.0 is that given that this hazard is a potentially lethal one, it deserves appropriate warnings and monitoring. ŠcutŠ.

Overarching Issues

The current crisis with SSRI agents has profound philosophical and methodological underpinnings that deserve better than ad hominem attacks. Current procedures to manage the entry of drugs onto the market favor the detection of drug effects and are biased against the detection of adverse effects. For instance, in order for a drug to be licensed it has to show superiority to placebo in two controlled trials. Companies, however, can run ten or more trials in carefully selected samples using instruments carefully designed to pick up any effect in order to demonstrate this, and even if the results show the drug failing to beat placebo in the clear majority of trials, this is not held against them. These other trials are commonly termed failed trials rather than drug failures. This was a live issue in the licensing of Zoloft as the Leber memoranda outlined above make clear.

In contrast, the demonstration of a safety issue is not handled in this way. In the case of safety, regulators only act if the overwhelming preponderance of the data show a hazard. These differences in approach have at their heart unresolved philosophical issues about the nature of statistics. Safety data are typically presented in terms of confidence intervals, so that, for instance, in recent antidepressant studies, the rate of suicides on drugs compared to placebo is typically of the order of two times greater but what is termed the confidence interval surrounding this figure of 2.0 might be anything from .9 to 4.4.

There are two ways to interpret such a finding. First, according to a school of thought stemming from R. A. Fisher, is the view that nothing has, in fact, been shown unless the confidence interval does not include 1.0‹for instance, only a confidence interval that shows a range from 1.1 to 4.4 for instance would be significant. Pfizer is relying heavily on just this point to claim that it has not been proven that Zoloft causes suicidal acts.

However, the Neymann-Pearson school of thought, and, in fact, the whole point behind confidence intervals, argues that the best estimate of the effect is 2.0, in this case, and that with a confidence interval of .9 to 4.4, while the data may be consistent with no effect, the scientific data are also consistent with a 4.4-times increase in risk. The 2.0 figure is the one regarding which we can be most confident and is the one that should dictate whether, for instance, warnings are placed on a treatment.

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