Samuel Johnson said that “the future is purchased by the present.”  And that’s as good a place to start as any in a discussion of the impact of direct-to-consumer advertising on the elderly.

According to recent polls, older Americans are more distrustful of the pharma industry and the FDA than the general population—and even more so in the wake of the current debate over drug safety.

Seniors want safe drugs—and rightfully so—but why are they more negative than other groups of Americans? I believe it is because throughout the significant majority of their lives, their only information about the medications they took came from a single source—their doctors. And the only information offered was how to imbibe the pill (with water, with food, minus alcohol, and the occasional caveat against operating heavy machinery). There was no doctor/patient discussion and there was certainly no public conversation.

That was the environment in which today’s senior citizens were born, grew into adulthood, married, raised children and grew grayer.

It was an environment where doctors were gatekeepers and the gate was kept tightly padlocked and second opinions were considered an affront to Marcus Welby, MD.

According to Juvenal, “All wish to possess knowledge, but few, comparatively speaking, are willing to pay the price.” Today we must face up to that dilemma.

Like it or not, America’s senior citizens are 21st century empowered healthcare consumers. Today, the “learned intermediary” has been replaced by the Internet, the patient is the purchaser, and Dr. Welby is a vendor. Managed care directs, “serious and life-threatening” diseases have morphed from polio and diphtheria to cancer, AIDS and Alzheimer’s Disease. There really shouldn’t be any wonder why older Americans—indeed, most Americans—are frightened. The entire healthcare paradigm has changed.

Woody Allen said that “Change is inevitable – except from vending machines.  Management guru W. Edwards Deming said that “Change is not required.  Survival is not mandatory.”

Change is frightening. In the 21st century, we must all be pharmacenti.  And that includes older Americans.

The Centers for Disease Control and Prevention National Health and Nutrition Examination Survey found that nearly one-third of people age 65 or older whom the survey found to have high cholesterol measurements said they had not before been told by a physician or other health professional that they had high cholesterol. Projected nationally, this percentage translates into about 2.1 million people who may have had high cholesterol without knowing it.”

Evidence is emerging that large numbers of elderly patients underuse needed medical care. According to a 2004 Health Affairs study that examined the “growing philosophical conflict over the abundance and inequities that characterize the U.S. health care system,” there is evidence of significant underuse of prescription drugs. The preponderance of published medical literature and clinical guidelines, according to the article, compels the expansion of pharmaceutical use among Americans.

This view is supported by a landmark RAND Health study published in The New England Journal of Medicine in June 2003, which found that prescription medications were underused in the treatment of seven conditions that clearly involve secondary prevention, including asthma, cerebro-vascular disease, congestive heart failure, diabetes, hypertension, and high cholesterol. These conditions produce many avoidable deaths, along with costly avoidable emergency room visits, hospitalizations, and nursing home admissions. Three of these conditions— diabetes, hypertension, and high cholesterol are now screened for under the new preventive services benefits now covered by Medicare.

Healthcare education and health literacy for older Americans is essential for both saving lives and saving our health care system.  And the best way to do both is to get older Americans to talk with their doctors – precisely the proven result of pharmaceutical direct-to-consumer advertising.

Health care information is the consumer’s Rosetta Stone – but older Americans shouldn’t need a Rosetta Stone to understand the avalanche of health care information that is available to them today. 

Dr. Ruth Day of Duke University speaks about the issue of “Cognitive inaccessibility” -- that health care information is disseminated in a way that is not only not understood by consumers but, worse, is misunderstood leading to unintended consequences. She reckons that only 20% of the information put out by FDA is properly comprehended. Her suggestion (among others) is that FDA initially focus on communicating better with health care providers.

When it comes to DTC advertising there is another type of cognitive issue – cognitive dissonance, specifically when it comes to information presented either via fair balance and adequate provision in television commercials, or the brief summary in print advertising.  And you know what they say, the brief summary is like the Holy Roman Empire – it is neither brief nor a summary.

In FDA’s 1999 study, 56% of people who saw a DTC print ad said that they read the brief summary “not at all” or “a little.”  In the 2002 study that number jumped to 73% -- a 17% increase.  During that same three-year span, those saying they read “Almost all” or “All” fell from 26% to 16%.

In 1999 3% said they weren’t aware that there even was a brief summary.  In 2002, that dropped a full decimal place to 0.3%.  In other words, more people know the brief summary is there, and fewer people are reading it. More information often results in less comprehension and, even worse, less interest.  When it comes to older Americans this is a crucial issue that must be addressed by academics, the pharmaceutical industry, and the FDA.  “In compliance” and “user-friendly” must not be mutually exclusive terms for anyone – least of all older Americans.

Consider the question posed by T.S. Eliot who asked,

"Where is the wisdom we have lost in knowledge? Where is the knowledge we have lost in information?”

An important op-ed from today's Wall Street Journal, penned by our friend Mark Thornton.

By MARK THORNTON

The news did not make it to the front pages, but on Feb. 28 a powerful member of the U.S. Senate launched an attack on the Food and Drug Administration, the drug companies and the desperate cancer patients they treat.

Charles Grassley (R., Iowa), ranking member of the Senate Finance Committee, requested that the Government Accountability Office launch an inquiry into whether the FDA behaved appropriately in granting the "accelerated approval" of Avastin, a drug for treating women with metastatic breast cancer. Mr. Grassley's action will have a catastrophic effect on America's ability to develop new drugs.

At issue is the concept of "surrogate endpoints" and the FDA's "accelerated approval" regulations. In the 1980s, at the height of the AIDS epidemic, AIDS activists were livid at the slow pace of development of new drugs to fight HIV. They lobbied heavily for changes in the law to allow an expedited pathway for the approval of new drugs for any disease deemed serious or life-threatening. The historic results were new laws and regulations that created an accelerated approval mechanism by which a drug could be allowed on the market if it showed early evidence of an effect on a surrogate endpoint. For cancer, examples of surrogate endpoints are tumor shrinkage or a delay in the disease's progression.

This kind of measurement – as opposed to an assessment of a drug's impact on a patient's overall survival – has dramatically increased the pace of cancer clinical trials. It also has won near-universal acceptance within the cancer community. The FDA does require follow-on studies to assure that a surrogate finding shows clinical benefit. But if all cancer clinical trials were required to show a survival benefit from the get-go, progress in cancer-drug development would slow to an absolute crawl.

Enter Mr. Grassley. It seems not a week goes by without him making a public accusation of evil doings within the drug industry or the FDA. Yes, Mr. Grassley did some good after the Vioxx episode, by focusing on the woeful manner in which postmarketing drug safety is managed and regulated by the FDA. But he and his staff should have kept their eyes on the ball. In the case of Avastin, the senator implied in his GAO request that something sinister occurred during the FDA's premarket deliberations, and that surrogate endpoints were the new bogeyman. Nothing could be further from the truth.

In February, the FDA approved Avastin despite a 5-4 vote by its Oncology Drugs Advisory Committee (ODAC) not to recommend approval. Meetings of this advisory committee address the most vexing issues that exist in cancer-drug development. The advice is usually helpful but never binding. Everyone who works at the FDA knows that the public only sees a fraction of what FDA insiders consider when they make their final decisions on products.

In the case of Avastin, additional data emerged late in the review process, after the ODAC meeting, that strongly supported accelerated approval. It became clear that Avastin had an enormous impact on the surrogate endpoint known as "progression-free survival." PFS is such a powerful measure that it is actually used as the basis for full approval in many cancer indications.

As part of the accelerated approval letter, the FDA also placed some of the most stringent postmarketing requirements in history for the drug's sponsor to gain full approval. No standards were lowered, and many women may now live much longer without their disease progressing.

The damage done by Mr. Grassley's decision to make an issue of this decision cannot be understated. Having served at the FDA during the Congressional hearings over the Imclone/Martha Stewart insider trading scandal, I can attest to how an action like this GAO inquiry will resonate within the halls of FDA. An extremely cautious and protective bureaucracy will respond to such intimidation by being even more protective.

The senator is demanding a full-scale review of each and every product ever approved, and is asking for a rejudgment by GAO "to ensure that drugs approved on surrogate endpoints are both safe and effective."

You can bet these bully tactics will have an effect. Look for greater demands by the FDA for cancer programs to not use the accelerated approval pathway. Just a few weeks ago, Medarex Inc. announced that the FDA will renege on a commitment to grant accelerated approval of a new product for skin cancer if its clinical trial showed benefit using the PFS endpoint. The FDA ordered a change toward the much stricter endpoint of overall survival, adding years to the time it will take to evaluate the drug's efficacy.

U.S. cancer-drug development stands on a precipice overlooking a new dark age in which each new product's development is longer and costlier than the last. Companies may decide it is not financially viable to even bother developing new drugs, and the pipeline for new products to treat cancer could slow even more. Mr. Grassley's legacy could be thousands of additional cancer deaths.

Advocates for all patients affected by Mr. Grassley's antidrug company demagoguery – including cancer patients, Alzheimer's patients, AIDS patients – must make their voices heard.

Dr. Thornton is a former medical officer in the Office of Oncology Products at the Food and Drug Administration. He volunteers as president of the Sarcoma Foundation of America.

"Too often medical reporters haven't been trained in the basics of understanding medical research and evidence-based medicine." 

So says Gavin Yamey, senior editor at PLoS Medicine.

This isn't to say there aren't some really terrific, highly aware ones out there as well -- there most certainly are. But they are in the minority.  If you agree with Gavin Yamey, the question then becomes, what's the best way to get reporters trained and who should do the training?

Should it be industry?  "Advocates?"  Academics?  Government officials?  Medical organizations?  Disease organizations?  Patient organizations?  Should there be a mandatory "health care for dummies" class in journalism schools?  The current practice, it seems, is on-the-job training.

The results (often inaccurate, sometimes slanted) are not a service to the health care information consumer (reader, viewer, listener). And there ain't no CME.

What's to be done?  Clearly one path is for reporters to reach out to various sources for background -- and to make sure those sources are diverse -- thus guaranteeing a variety of opinions and avoiding undue, single-source bias.

In fact, now that I think of it, that's probably a good idea for all health care reporters -- even those with well-known and well-read bylines.

FDA Proposes New Rule to Provide Updated Information on the Use of Prescription Drugs and Biological Products during Pregnancy and Breast-feeding

The U.S. Food and Drug Administration today proposed major revisions to the physician labeling for prescription drugs (including biological products) to provide better information about the effects of medicines used during pregnancy and breast-feeding.

The proposed changes to prescription drug labeling would give health care professionals more comprehensive information for making prescribing decisions and for counseling women who are pregnant, breast-feeding, or of child-bearing age about using prescription medications.

Although physician labeling is directed to health care professionals, it is sometimes adapted for use in consumer-directed labeling such as patient package inserts or medication guides when such labeling is approved for a prescription drug.

"With this proposal, FDA's goal is to help women, their physicians and their pharmacists have better information about the effects of prescription medicines so that pregnant women, nursing mothers, and breast-feeding infants will benefit,” said Rear Admiral Sandra Kweder, M.D., Center for Drug Evaluation and Research, FDA. “This proposal would help make drug labeling a better communication tool, and would potentially have a huge impact on public health and well being for women.” 

There are about six million pregnancies in the United States every year, and pregnant women take an average of three to five prescription drugs during pregnancy. Additionally, women with pre-existing medical conditions, such as asthma or high blood pressure, may need to continue to use prescription drugs to treat those conditions during pregnancy.

The proposed rule outlines what important information about the use of medicines during pregnancy and breast-feeding would be required to be added to product labeling for newly approved drugs. Under the proposal, drug labeling would explain, based on available information, the potential benefits and risks for the mother and the fetus, and how these risks may change during the course of pregnancy.

In the 1990s, the FDA recognized the shortcomings of pregnancy and breastfeeding information in prescription drug labeling and began reviewing ways to improve the information. The agency held public meetings and focus groups to obtain comment on the current labeling from health care professionals and scientific experts. Current labeling uses a letter category system to describe the risks of drug use during pregnancy. Stakeholders have said the letter category system leads to an inaccurate and overly simplified view of these risks, and does not facilitate updating of labeling as new information becomes available.  

The proposed rule would remove the letter categories from the pregnancy section of prescription drug labeling. The newly designed format, for the pregnancy section of the labeling would have three sections:

--The first section, called the "Fetal Risk Summary," would describe what is known about the effects of the drug on the fetus, and if there is a risk, whether this risk is based on information from animals or humans. The proposal calls for a risk conclusion based on the available data and provides a number of examples depending on the quality and quantity of that data. For example, one risk conclusion might be: “Human data indicate that (name of drug) increases the risk of cardiac abnormalities.” This would be followed by a summary of the most important data on the drug’s effects.

--Another section, called "Clinical Considerations," would include information about the effects of the use of the drug if it is taken before a woman knows she is pregnant. This section also would feature discussions about the risks of the disease to the mother and the baby, dosing information, and tell how to address complications.

--The third section, under the heading "Data," would describe in more detail the available data regarding use of the drug in humans and from animal studies that were used to develop the Fetal Risk Summary.

The pregnancy section would also include information about whether there is a pregnancy exposure registry for the drug. Pregnancy exposure registries collect and maintain data on the effects of approved drugs that are prescribed to and used by pregnant women.

The lactation (breastfeeding) section of prescription drug labeling would use the same format as the pregnancy section. The lactation section would provide information about using the drug while breastfeeding, such as the amount of drug in breast milk and potential effects on the breastfed infant.

Certain newly approved drugs would use the new pregnancy and lactation labeling format, while labeling for previously approved drugs will be phased in gradually under FDA’s recent Physician Labeling Rulemaking.

JAMES A. BIANCO
GUEST COLUMNIST