The FDA announced today that it will post, quarterly, a report of drugs that are being evaluated for potential safety problems.  The FDA will base this list on adverse events reported through the agency’s Adverse Event Reporting System (AERS). The first report will be posted today.

This reporting mechanism is a requirement of FDAAA.

Ultimately, based on these evaluations, the FDA can require next steps ranging from (1) nothing – if the adverse events are determined not to be drug-related, (2) a risk management plan (REMS), (3) a label change, up to and including (4) a Phase IV clinical trial. It's important to note that all of these options can now, per FDAAA, be mandated by the agency.

This news was presented by Paul Seligman, MD (Associate Director of Safety Policy and Communication, CDER) and Gerald Dal Pan, MD (Director, Office of Surveillance and Epidemiology).  Both commented on the need to keep these warnings in perspective and both spoke to the issue of unintended consequences and that the agency would strive to communicate the information in the manner designed to avoid misinterpretation by patients and overreaction by the media.

(If you disagree that the media overreacts, let's see what happens tomorrow.)

One way to help modulate the unintended consequences (aka, "general hysteria") these things tend to generate is to make sure drug companies have some advance warning of these postings so they can be prepared to communicate their perspectives to patients, physicians and payers.  Will the FDA be advising companies that a given product will be included in the report?  It wasn't discussed during the press briefing.

Inquiring minds want to know (1) if "yes," how far in advance will a company be notified and, (2) if "no," why not?

More as more develops.

On September 22 in Washington DC, the Center for Medicine in the Public Interest is hosting a half-day conference on pharmaceutical industry support of continuing medical education.  We'll address some key questions such as:

* Is it "true" that industry-sponsored CME helps neither physicians nor patients because it is "biased?"

* Would CME be "better" if industry just gave the same dollars to academic medical centers and hospitals?

* Does barring industry support dampen intellectual freedom and drive talented people out of academic medicine?

We'll be joined by experts such as Tom Stossel, MD (Professor of Medicine, Harvard Medical School), Roger Meyer, MD (Clinical Professor of Psychiatry, Georgetown University), Jack Lewin, MD (President, American College of Cardiology), Gary Puckrein (National Minority Quality Forum), Michael Weber, MD (Professor of Medicine, Downstate Medical Center) and others.

We hope to see you there.  Here's a copy of the complete agenda. 

If you would like to attend (there is no cost), please contact Mario Coluccio at (212) 417-9169 or mario.coluccio@cmpi.org

As difficult as it is for parents who have lost children to suicide, the truth is the truth and cannot be ignored.

Consider today's story in the Wall Street Journal:

Elevated Rate Of Teen Suicide Stirs Concern

 
Trend Is Linked to Drop in Use Of Antidepressants After FDA Raised Worries About Risks

By SARAH RUBENSTEIN

A new study may bolster the argument that a drop in the use of antidepressants has led to an increase in teen suicides. Researchers said an analysis that included 2005 data -- the latest available -- shows that a surprising rise in the youth suicide rate in 2004 was largely sustained into the next year. While the rate dropped somewhat in 2005, researchers said, it remained higher than expected. The rise in suicides coincided with Food and Drug Administration advisories about antidepressants that led to an October 2004 decision to require strong "black box" warnings on all antidepressants' labels.

MAKING SENSE OF TEEN SUICIDE

How a trend changed direction.

1990-2003: The suicide rate for people 10 to 24 years old slid more than 28%.

2003-2004: The FDA issued advisories on antidepressants and required 'black box' warnings on labels.

2003-2004: The suicide rate for young people rose 8%.

2004-2005: The teen suicide rate slipped but remained elevated.

Last fall, the U.S. Centers for Disease Control and Prevention said the suicide rate for 10-to-24-year-olds rose 8% from 2003 to 2004 -- after a cumulative drop of more than 28% from 1990 to 2003. The CDC cautioned at the time that it didn't know if the rise was "short-lived" or the "beginning of a trend."

The CDC has monitored the data since then but hasn't come to a conclusion, saying several years of data are needed. But the new analysis by outside researchers suggests the increase "was not a single-year anomaly" and may reflect "an emerging public health crisis," according to a paper being published in Wednesday's Journal of the American Medical Association.

"We're seeing [more than] 600 more suicides in this two-year period than we would have expected, and that is cause for concern," said JeffreyBridge, an epidemiologist at the Research Institute at Nationwide Children's Hospital in Columbus, Ohio, and lead author of the study. A co-author was Joel Greenhouse, a statistician at CarnegieMellon University in Pittsburgh.

The latest analysis could rekindle controversy over the FDA's decision to require the "black box" warnings, which link the drugs to suicidal thoughts and behavior in young people. The warnings, along with the agency's concerns about antidepressants, contributed to a drop in prescriptions of the drugs for children and adolescents. The thorny question for doctors and patients: Are concerns about antidepressants scaring people away from medicines that could help them?

"We've seen this increase as soon as these warnings started, and it is what we were most worried about," said Kelly Posner, a researcher in ColumbiaUniversity's psychiatry department who has helped the FDA collect data on antidepressants and suicide and who says she doesn't have any financial ties to drug companies. "If you look at the whole evidence puzzle, it points in one direction -- antidepressants save lives."

Still, it's unclear whether a drop in antidepressant use is what caused the rise in the suicide rate. The suicide rate pertains to the entire population and doesn't indicate who took antidepressants and who didn't.

Other factors possibly contributing to the rise in the teen suicide rate include alcohol use, access to firearms, the influence of Internet social networks and suicides among U.S. troops, some of whom are older adolescents, Dr. Bridge wrote in the JAMA paper. His study was funded by the U.S. National Institute of Mental Health.

However, responding in part to concerns about avoidance of antidepressants in cases where they're needed, the FDA in 2007 called for an update to the boxed warning, adding that depression and certain other serious psychiatric disorders are themselves the most important causes of suicide. "It is our intent to fully inform prescribers about the risks and benefits of antidepressant prescribing -- not to discourage appropriate prescribing," FDA spokeswoman Sandy Walsh said.

Still, Ms. Walsh said, while the FDA continues to monitor data around the issue, it remains "confident the data support warnings" about suicidal thoughts and behavior in young people, and "it's still good advice to monitor patients starting treatment."

Suicide rates are calculated per 100,000 people. The rate for 10-to-19-year-olds was 4.49 per 100,000 in 2005, down from 4.74 per 100,000 in 2004. However, if the 2003-2004 rise were indeed a fluke, the 2005 figure would have been around 3.8 per 100,000, Dr. Bridge said. In 2003-2004, the increase in the suicide rate among people 10 to 19 was much sharper than the rise in the rate for 20-to-24-year-olds.

Still, the CDC is approaching the data cautiously. Alex Crosby, a medical epidemiologist at the CDC's InjuryCenter, said that in addition to watching the suicide figures, the agency is analyzing data from its National Youth Risk Behavior Survey of high-school students conducted every two years and its National Violent Death Reporting System, which includes details on the circumstances of suicides in 17 states.

The CDC has ramped up efforts aimed at Hispanic adolescents, who report a greater percentage of suicide attempts than other groups, and at Native Americans, who have the highest suicide rate among adolescents and young adults.

Now let's wait and see what the anti-SSRI mafia has to say.  You can bet it'll be vitriolic pharma-bashing with a heaping measure of junk science.

The truth hurts.

As you can see from the blog entry “What Depression, Measles and Sir Isaac Newton have in common”, there’s a new voice on drugwonks – Dr. Tim Franson.

Recently retired after 22 years of service at Eli Lilly & Company (most recently as Vice President for Global Regulatory Affairs), Tim was one of the original architects of PDUFA.  He was also one of the first people the FDA recruited to discuss the nascent concept of the Critical Path.  He loved the idea but also helped to identify some of the problems.

Tim is a guy who, as the old Jewish joke goes, "knows where the rocks are."

His regulatory knowledge is nonpareil and his optimism is contagious.

It is therefore, with great honor and excitement, that we announce that Dr. Franson has joined the Center for Medicine in the Public Interest (the public policy home of drugwonks.com) as a senior fellow.

Among his many achievements, Tim has served on Drake University's Task Force on the College of Pharmacy and Health Sciences and is currently a member of the College of Pharmacy Dean's Advisory Board for Auburn University. Dr. Franson has authored over 50 articles and one text in the fields of infectious disease, epidemiology, pharmacoeconomics, and antibiotic utilization. He is board certified in Internal Medicine and Infectious Diseases.

We welcome his compassion, intelligence and commitment to the public health.

On the surface, the disease states of depression and measles could not be more dissimilar. Measles, a viral infection usually afflicting children at an early age, is typically an acute, self- limited disorder with a striking skin rash easily recognized by trained health professionals, and effectively prevented by insidious conditions with periodic worsening which impact all ages   (though most frequent in adult females) which have no visible signs on physical examination and are not amenable to primary prevention.

What these two medical entities share are the risk of serious complications if not properly managed - and their plight in the health policy arena as byproducts of the "law of unintended consequences".

As a result of concerns about alleged overtreatment of depression  in adolescents and a suspected risk of suicidal ideation related to  therapy - fueled by congressional hearings and media attention, with resultant restrictive labeling additions by FDA several years ago - antidepressant therapy in this population has decreased.  Recent surveillance studies indicate that for the first time in a decade, the rate of adolescent suicide attempts has risen … whether this potential temporal relationship of "reduced use-to-increased suicide attempts" is valid does require more careful study to be validated, but it is tempting to speculate that some cause and effect link may be present.

Likewise, accusations of childhood vaccines (notably those containing mercurial preservatives) being associated with causing autism have frequently surfaced over the past few years. While  extensive studies by WHO and other authorities have found no evidence of vaccines being associated with autism, this concern continues to be highlighted by very vocal congressional and media sources -- and seemingly has created a "parental flinch" resulting  in the reduced prevalence of childhood vaccine use in some communities. In the past week, reports have come to light regarding an increased incidence of measles cases in the US and elsewhere compared to previous years - a distressing development in the eyes of those who remember the devastating complications which occurred  associated with measles outbreaks in years past. Cause and effect?

 In both situations, there is no question that the actions of those in Congress and the media were well-intentioned and taken based on their perspective of drug/vaccine safety issues being a priority concern.

However, as Sir Isaac Newton correctly observed centuries ago, "For every action, there is an equal but opposite reaction.” An undue focus on safety concerns, to the exclusion of a broader consideration of benefit-risk tradeoffs is fraught with disastrous, unintended consequences. Did the potential benefits of overall vaccine and antidepressant use get equal consideration in the conduct of these policy debates and decisions? Were voices raised about the importance of looking at long term as well as immediate impact of deliberations founded on "safety in isolation"? If so, those kind of tempered thoughts were not reflected in the accounts reaching the general public, which certainly can provide an incomplete, misleading basis for parents considering the upsides vs. risks for medical interventions proposed for their children.

The public health would be better served by policy decisions in which [1] no decisions are made based on safety alone, with a reinforcement of thoughtful benefit-risk assessments being the platinum yardstick (as they are done at the bedside of any patient) and [2] decisions are coupled with appropriate follow-up monitoring to ensure that unintended consequences do not surface as a result of such recommendations - and if such do occur, to promptly revisit such matters using careful reconsideration, with corrective actions as warranted (just as physicians do in managing a patient's conditions over time). Such approaches would not diminish the attention given to new safety findings, but would encourage more balanced actions. Our vision skills are best when employing both eyes, and monocular outlooks on life often lead to blind spots -- our vision of health policy deserves similar insight.

During my medical career, I frequently heard sage faculty admonish trainees to understand their limitations and not to fall into the trap of "doctors playing God" -- the converse also holds true, for when influential policy gods play doctor, power trumps knowledge … in both such scenarios, accountability is lost and Newton's Third Law cannot be appealed. Kids deserve better.