The Food and Drug Administration approves a label for every drug marketed in the United States. “The FDA approved label is the official description of a drug product which includes indication (what the drug is used for); who should take it; adverse events (side effects); instructions for uses in pregnancy, children, and other populations; and safety information for the patient. Labels are often found inside drug product packaging.” While physicians may prescribe FDA approved drugs for off-label uses, it is illegal for the manufacturer to market one of its drugs for an off-label use.

John Carreyrou writes in the November 3, 2006, Wall Street Journal that while off label prescriptions may not be illegal, they can be dangerous to the patient’s health. He uses the powerful painkiller Actiq, which he describes as a highly addictive “narcotic lollipop” with an active ingredient fentanyl that is 80 times more powerful than morphine. Cephalon markets Actiq. The San Francisco Chronicle features today a first person account of Actiq abuse.

Actiq was approved for marketing in 1998. Its sales volume climbed from $15 million in 1999 to $412 million in 2005.

The Wall Street Journal story explains that

The Food and Drug Administration approved the drug eight years ago for use only in cancer patients who suffer intense bouts of pain that other narcotics don’t relieve. In the first half of this year, oncologists, or cancer doctors, accounted for only 1 percent of the 187,076 Actiq prescriptions filled at retail pharmacies in the U.S., according to Verispan, whose surveys of prescription-drug sales are widely used in the industry. Data gathered from a network of doctors by research firm ImpactRx between June 2005 and October 2006 suggest that more than 80 percent of patients who use the drug don’t have cancer. Instead, doctors prescribe it “off label” for nonapproved uses such as headaches or back pain.Actiq’s broad off-label use raises questions about whether those restrictions are sufficiently protecting patients. “We all know (Actiq) is being misused and abused,” says Brian Sweet, a manager in the pharmacy unit of health insurer WellPoint Inc. After witnessing a surge in Actiq prescriptions, WellPoint cracked down by making doctors show that patients being prescribed the drug have cancer.

The U.S. Attorney for the Eastern District of Pennsylvania is investigating Cephalon’s marketing practices, according to the Journal.

The AP reports that the U.S. Centers for Disease Control have announced that there is no longer a shortage in the meningitis vaccine, Menactra, manufactured by Sanofi Pasteur. Last year, after the Food and Drug Administration approved Menactra for marketing, the CDC recommended that three age groups — college freshmen, teens entering high school and children aged 11-12 — receive the vaccine. In May 2006, the CDC delisted preteens due to a vaccine shortage. That shortage now has been resolved and the CDC has reinstated its recommendation that children aged 11 – 12 receive the vaccine.

Steven Pearlstein assesses the CVS / Caremark merger in the Washington Post this morning. Analysts predict that the merger will survive government antitrust review. Both companies announced strong third quarter earnings yesterday. The merger is expected to close next year.

Joseph Conn reports in Modern Healthcare.com that the American Health Information Community (AHIP) at its October 31 meeting gratefully accepted the Health Information Technology Standards Panel’s work product: “22 standards and eight implementation specifications to support data transmissions in three areas selected by AHIC: to move lab data into electronic health-records systems; to populate personal health records with a patient’s medication history and basic information to facilitate registration; and to speed the transfer of healthcare information from providers to public-health authorities for biosurveillance.” He also reports controversy over the lab data transfer standards.

Dr. Elliot Fisher, a professor of medicine at Dartmouth, wrote an interesting opinion piece on Medicare’s pay for performance programs in the Nov. 2 issue of the New England Journal of Medicine. Dr. Fisher provides a medical community perspective on the long term goals for pay for performance inside and outside of Medicare.

Laura Landro reports in the Wall Street Journal today that “a coalition of health-care purchasers, quality groups and government agencies working with the National Quality Forum, the leading government advisory body on health-care quality measurement and standards, have agreed for the first time to endorse a single set of 30 ‘safe practices’ that all hospitals should use to prevent death and injury to patients.” That’s progress.

What was hinted at this morning became reality this afternoon when CVS, a major pharmacy chain which has a prescription benefit manager affiliate Pharmacare and a major PBM Caremark announced their merger. Caremark shareholders will receive 1.67 shares of CVS stock for each of their Caremark shares. The new company will be called CVS /Caremark and it will be headquartered in Woonsocket, Rhode Island (gateway to the Taunton). The stock swap deal is valued at $21 billion and the projected 2006 revenues for the combined company are $75 billion. The Wall Street Journal notes that CVS has been very acquisitive this year and that PBM stocks have been down since September when Walmart announced its $4 generic prescription price. The proposed settlement in the AWP price fixing litigation has added to the PBM stock woes as discussed in the blog last week.

The AP reports that

Glenn Garmont, an analyst with First Albany Corp., said before the announcement that the deal was likely spurred in part by the fear that Wal-Mart, “will emerge as a fierce new competitor following its introduction of selected $4 generic drugs.” Wal-Mart announced last week that it is extending its $4 for a one-month supply of 314 different generic prescriptions to make the program available at 1,008 stores in 27 states. However, [CVS CEO Tom] Ryan and [Caremark CEO Tom] Crawford said Wal-Mart’s action didn’t affect their decision to merge. “We’ve been working on all this for some time,” Crawford said. “This didn’t have anything to do with Wal-Mart.” Garmont said such a deal between Caremark and CVS “would spawn others, and we view all PBMs … as potential take-out targets.” Still, some analysts said the deal might face antitrust concerns. Barry Barnett, a health care consultant for PricewaterhouseCoopers, said regulators might be concerned that Caremark might unfairly funnel business to CVS pharmacies at the expense of other drug stores.

Several years ago Caremark acquired Advance PCS, one of the original PBMs. Earlier in its history, PCS had been owned by a drug manufacturer Eli Lilly, a drug wholesaler McKesson, and a pharmacy chain Rite Aid. None of those arrangements were profitable, as I recall. Another major PBM Medco recently split away from its drug manufacturer parent Merck a few years ago following considerable antitrust scrutiny. So the experience of this new combination will be worth following.

The Wall Street Journal and the New York Times are reporting this morning that a major pharmacy chain CVS (which has its own prescription benefit manager operation) and one of the largest PBMs Caremark are in merger talks.

Caremark and CVS confirmed the talks in this joint press release:

NASHVILLE, Tenn. and WOONSOCKET, R.I., Nov. 1 /PRNewswire-FirstCall/ — Caremark Rx, Inc. (NYSE: CMX) and CVS Corporation (NYSE: CVS) confirmed today they are engaged in discussions relating to a possible merger of equals transaction. There can be no assurances that any agreement will be reached or that a transaction will be consummated. There will be no further comment until the discussions are concluded.

From 1938 to 1962, federal law permitted manufacturers to market drugs that had been tested for safety. In 1992, Congress amended the law to require that the Food and Drug Administration approve drugs for marketing based on evidence of safety and efficacy. (Click here for an historical timeline of FDA regulation.

In 1968, the FDA commissioned the Drug Efficacy Study Implementation (DESI) that identified 3,400 active drug ingredients marketed between 1938 and 1962 that were safety tested but not proven effective. The FDA explains that

“One of the early effects of the DESI study was the development of the Abbreviated New Drug Application (ANDA). ANDAs were accepted for reviewed products that required changes in existing labeling to be in compliance. In September 1981 final regulatory action had been taken on 90% of all DESI products. By 1984, final action had been completed on 3,443 products; of these, 2,225 were found to be effective, 1,051 were found not effective, and 167 were pending.”

Federal law permits the manufacturer to continue to market DESI drugs until the FDA deems the drug unapproved based on lack of efficacy following notice and a hearing.

Forty years later, the FDA has not completely closed the loop on these DESI drugs. The FDA’s web site explains that

For a variety of historical reasons, some drugs, mostly older products, continue to be marketed illegally in the United States without required FDA approval. Many healthcare providers are unaware of the unapproved status of some drugs and have continued to unknowingly prescribe unapproved drugs because the drugs’ labels do not disclose that they lack FDA approval. Often these drugs are advertised in reputable medical journals or are included in widely used pharmaceutical references such as the Physicians’ Desk Reference (PDR).

The FDA recently released compliance guidance on unapproved drugs and plans a workshop in January 2007.

BNA reports that Sen. Charles Grassley (R – Iowa), Chairman of the Senate Finance Committee, is concerned that the compliance guidance “estimates that there are several hundred unapproved active ingredients in drugs currently on the market”, and he is pressuring the agency to remove these drugs from the market.

The Wall Street Journal reports today on several web sites that adults can use to calculate their health risk for various diseases. The Journal highly recommends a comprehensive risk assessment site created by the Harvard Center for Cancer Prevention. The site called “Your Disease Risk” also offers an customized action plan. I just tried to log onto the site, which has been receiving 2000 visits per day and the Journal article has crashed the site. So try it out in a few days.

The Journal gives honorable mention to a heart attack risk assessment offered by the American Heart Association and a breast cancer risk assessment offered by the National Cancer Institute.