Last checked at 
By Toni Clarke
WASHINGTON, May 6 (Reuters) - The U.S. Food and DrugAdministration will hold a public meeting this summer to addressdrug company concern that restrictions on what they can sayabout off-label use of drugs violate their first amendment rightto free speech.
The meeting, announced last month by FDA chief counselElizabeth Dickinson, comes as a bill known as 21st CenturyCures, designed to speed new drugs to market, is moving throughCongress. Language in the bill is adding pressure on the agencyto relax its guidelines.
Efforts by drug companies to change the rules gained steamafter a 2012 decision from the Second Circuit Court of Appeals,which overturned the conviction of Alfred Caronia, a salesrepresentative for Orphan Medical, which was later acquired byJazz Pharmaceuticals Inc. After Caronia was caughttalking to physicians about various off-label uses of thenarcolepsy drug Xyrem, the court said the First Amendmentprotected truthful and non-misleading off-label speech.
Under current rules, physicians are allowed to prescribemedicines off-label for whatever condition they want. But drugcompanies are not allowed to promote them for uses that have notbeen approved by the FDA.
Pharmaceutical companies are citing the Caronia and similarrulings to pressure the FDA to let them talk more freely aboutoff-label use.
"If you're a community physician it's hard to stay current,"said Coleen Klasmeier, a partner at Sidley Austin LLP, whichpetitioned the on behalf of a coalition of pharmaceuticalcompanies to "adequately justify and appropriately tailor itsregulatory regime" in light of Caronia and similar rulings.
The coalition, known as the Medical Information WorkingGroup, includes Pfizer Inc, Sanofi, NovartisAG, Johnson & Johnson, Eli Lilly and Co and GlaxoSmithKline Plc, among others.
At stake are billions of dollars in potential sales ifmanufacturers can persuade physicians to use their products forunapproved uses and a potentially significant weakening of theFDA's regulatory authority.
Karen Riley, an FDA spokeswoman, said the agency decided tohold a public meeting "because of the wide range of views heldby different stakeholders and the importance of the underlyingpublic health issues."
OFF-LABEL PROMOTION
Drug companies have a long history of breaching theoff-label rules. Over the past decade 17 companies paid morethan $16 billion in settlements for off-label promotion,according to the American Medical Association, including Pfizer,GlaxoSmithKline and Eli Lilly.
In September, Shire Plc agreed to pay $56.5 millionto settle charges it overstated the benefits of its attentiondeficit disorder drug Adderall XR and claimed, with littleevidence, that it would prevent criminal behavior, trafficaccidents and sexually transmitted disease.
"At my own medical center we have banned pharmaceutical repsfrom coming because we don't think they are a good source ofinformation," said Dr. Rita Redberg, professor of medicine atthe University of California, San Francisco, and editor of themedical journal JAMA Internal Medicine. "You don't ask thebarber if you need a haircut."
Off-label use already accounts for 10 percent to 20 percentof prescribing, with that figure rising in oncology andpediatric rare diseases, according to the AMA, which said it"supports the important need for physicians to have access toaccurate and unbiased information about off-label uses of drugsand devices, while ensuring that manufacturer-sponsoredpromotions remain under FDA regulation."
REPUTABLE JOURNALS
The FDA does allow companies to provide doctors with datafrom well-controlled clinical trials from reputable medicaljournals and reference texts (but not from early clinical trialsor letters to editors) and they can talk about off-label use atmedical conferences. They can also respond to unsolicitedquestions from physicians as long as the responses do not toutthe benefits of a product without disclosing its risks.
Companies want to be able to discuss data that does not comefrom randomized clinical trials. They also want to be able toprovide economic analyses to insurance companies showing why adrug should be covered.
"Let's say a drug is very expensive and very effective anddoesn't have many side effects," Klasmeier said. "If you're ahealth plan and you are trying to decide whether to pay for thedrug you want to know how it stacks up against others."
Industry pressure has "forced the FDA to think harder aboutthis topic," said Peter Pitts, a former FDA associatecommissioner for external relations, who is now president of theCenter for Medicine in the Public Interest, a think-tank thatreceives funding from drug companies.
In response to petitions from the coalition, the FDA notedthat its regulatory framework was developed "in response topublic health tragedies" but said it "recognized the evolvinglegal landscape in the area of the First Amendment" and promisedto review its policies.
It has proposed adding clinical practice guidelines to thelist of material companies can circulate. These are oftendeveloped by professional associations and may include treatmentand dosing regimens that differ from what is on a drug's label.
It has also proposed allowing companies to distributemedical literature showing a product's side effects to be lessthan described in the label. Comments from the public inresponse to the proposal were overwhelmingly opposed, accordingto documents obtained and made public by the consumer watchdogPublic Citizen.
TRUTHFUL BUT NOT MEANINGFUL
Those moves have not been enough to appease the industry.Yet public health advocates fear that if the FDA yields further,companies may be able to circulate data which is truthful underthe Caronia definition without being meaningful for patienthealth.
A 2012 study showed that up to 75 percent of publishedpreclinical trial results could not be reproduced in subsequenttrials. An earlier one showed that when scientists attempted tocorroborate 34 claims from frequently cited published trialsthey were unable to do so 41 percent of the time.
"People do not realize that the consequences of this newideological approach to the First Amendment will be measured inlives," Dr. Joshua Sharfstein, a former principal deputycommissioner at the FDA who is now associate dean at JohnsHopkins Bloomberg School of Public Health.
For example, doctors prescribed schizophrenia and bipolardisorder drugs for years to control behavior in elderly patientswith dementia. Studies later showed they increased the rate ofdeath in the elderly.
Premarin and Prempro, drugs to treat symptoms of menopause,were prescribed extensively to women for years on the assumptionthey would prevent increased coronary disease. The hypothesiswas supported by some data but not by randomized, controlledclinical trials. When the drugs were eventually analyzed in alarge government-sponsored trial they were found to increase therisk of stroke and heart attack.
If companies can market drugs for off-label uses there willbe no incentive for them to conduct the clinical trials neededto show the products work and are safe, critics say.
"If off-label marketing is allowed then drugs will come tobe used for a wide variety of conditions for which there has notbeen developed evidence of safety and efficacy," said Dr. StevenNissen, chairman of cardiovascular medicine at the ClevelandClinic. "You take away those checks and balances and it's thewild, wild west."
(Reporting by Toni Clarke in Washington. Editing by MicheleGershberg and John Pickering.)
