E-DRUG: off-label use and free (commercial) speech?

["Marita van Rooyen" <vrooym@hltrsa.pwv.gov.za>]

E-drug: off-label use and free (commercial) speech?
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[this is a very interesting debate. Off-label use (using a drug for a 
non-approved indication or a non-approved age category) is quite 
widespread, especially among paediatricians. Science is dynamic and 
Drug Regulatory Authorities are often slow to incorporate changes, 
especially if the drug company involved does not formally request to 
legalize the off-label use (any change in the registration file needs 
evidence and costs money, and why spend money when the target group 
is already prescribing your product?).
I will be interested to hear how other countries have tackled this 
issue of off-label use and free speech. WB]


Dear E-druggers,

What is the situation in your countries?

Marita
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FDA's Role Limited in Prescribing Drug Use 

By Guy Gugliotta
Washington Post Staff Writer
Thursday, July 29, 1999; Page A1 

[reproduced as fair use; WB]

In a decision with potentially far-reaching implications for how 
doctors prescribe drugs, a federal judge ruled yesterday that the 
Food and Drug Administration cannot stop the pharmaceutical industry 
from encouraging physicians to use medications for unapproved
purposes. 

The ruling will further curb the FDA's already limited ability to 
control so-called off-label use of medications and allow companies to
conduct seminars for physicians and distribute information to them 
about a drug as long as the FDA has approved it for some purpose. 

Doctors are already allowed to prescribe any drug for use once it has 
been approved by the FDA for some use. The new ruling means that
drug companies will be freer to more aggressively promote this 
practice, which can yield both spectacular benefits and catastrophic 
tragedies. 

On July 20, for example, the New England Journal of Medicine rushed 
into publication a report that spironolactone, a drug used for 40 
years in the treatment of water retention, cut death rates  
dramatically as an "off-label" treatment for congestive heart 
failure. 

But Georgetown University pharmacology chief Raymond Woosley noted 
that powerful drugs designed to treat severe heart rhythm 
irregularities were still being prescribed off-label for "trivial 
arrhythmia" even after they had caused 50,000 deaths by some
estimates. Sales of one of these drugs were stopped in 1989, but 
another one, Tambacor, is still on the market. 

U.S. District Judge Royce C. Lamberth's memorandum yesterday ruled 
unconstitutional portions of last year's Food and Drug Administration 
Modernization Act that regulate the pharmaceutical industry's ability 
to distribute information on off-label drug applications. 

"The government, however benign its motivations, simply cannot 
justify a restriction of truthful, nonmisleading speech on the 
paternalistic assumption that such restriction is necessary to 
protect the listener from ignorantly or inadvertently misusing the 
information," Lamberth wrote. 

Jeff Trewhitt, spokesman for the Pharmaceutical Research and 
Manufacturers of America, said that the drug companies were
"reviewing this decision," and "it would appear the judge's ruling is 
consistent with the constitutional protection of commercial
speech." 

The FDA also limited itself to a brief comment: "We'll have to 
carefully evaluate the decision and determine what we have to do as a
follow-up," said Peggy Dotzel, the FDA's acting associate 
commissioner for policy. But Dan Troy, one of the lawyers for the
Washington Legal Foundation, plaintiffs in the case against the FDA, 
called Lamberth's ruling "total vindication of our position." He said
he expected the FDA to appeal. 

The foundation, a free-market advocacy group that Troy said does not 
represent the pharmaceutical industry, filed suit against the FDA in 
1994 over the agency's guidelines on promotion of off-label drug 
uses. 

In a summary judgment one year ago, Lamberth found the FDA's 
guidelines unconstitutional. But after passage of the FDA 
Modernization Act, Lamberth agreed to review his ruling. 

The redrawn guidelines contained in the law allowed pharmaceutical 
companies to disseminate peer-reviewed journal articles and
texts to doctors as long as the firm met a list of conditions. 

The law included a provision requiring the manufacturer to apply to 
the FDA for a new application for a drug before promoting it.
Another provision required the manufacturer to submit promotional 
materials to the FDA for review before distribution. A third required
the manufacturer to report semiannually on its promotional 
activities. 

Lamberth rejected all of these requirements as indefensible 
violations of the Constitution: "The supplemental application 
requirement of the act amounts to a kind of constitutional
blackmail," Lamberth wrote. "Comply with the statute or sacrifice 
your First Amendment rights." 

The pharmaceutical companies' Trewhitt said that the industry 
interpreted Lamberth's finding narrowly ? confirming "the right of a
company to give a reprint of a medical journal article to a doctor" 
as long as it is not "false or misleading" and as long as the
company "discloses its interest in the drug" and notes that the 
application does not have FDA approval. 

Still, Georgetown's Woosley explained that the problem for the FDA is 
that a drug company unfettered by government regulation is
unlikely to disseminate information that does not support its cause. 

"We see all the time that advertising and promotion of medications 
exceeds the bonds of scientific accuracy, and you have to address
it one way or another," Woosley continued. "Physicians need to know 
about off-label applications, but they need balanced information, and 
there is no impartial arbiter" that can give it to them. 

This has left the FDA with two bad options ? abandon the field to the 
industry, or try to restrict its access to physicians and risk the
wrath of the Constitution. "We thought it was kind of silly," said 
one congressional source knowledgeable about the drafting of the FDA
Modernization Act. "How do you tell doctors what to read?" 

© 1999 The Washington Post

---
Marita van Rooyen
Essential Drugs Programme - Resource Centre
Room 936/916 Hallmark
Department of Health
Private Bag X828
Pretoria0001
South Africa
+27 12 312 0006 tel
+27 12 324 4525/324 7501 fax
vrooym@hltrsa.pwv.gov.za
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