By Peter Montague
A report in the Journal of the American
Medical Association
The report included only drugs that were given properly and under normal circumstances, excluding any administered in error or taken in attempted suicides.
The sale of prescription drugs has more than doubled in the US during the past eight years. In 1990, people in the US spent US$37.7 billion on prescriptions; in 1997, national spending on prescriptions reached US$78.9 billion.
Prescription drugs are the fastest growing portion of health-care costs, having risen at the rate of 17% per year for the past few years.
Urging physicians to prescribe particular drugs — especially new drugs — is a huge business. According to the New York Times, in 1994, there were 35,000 full-time "detail people" employed by drug companies to visit doctors and describe pharmaceutical products; by 1998, the number had grown to 56,000 — one sales person for every 11 physicians.
Drug companies spent US$5.3 billion in the first 11 months of 1998 sending their "detail people" into doctors' offices and hospitals, plus another $1 billion putting on "marketing events" for doctors.
Testing
Not all adverse reactions to new drugs can be anticipated or avoided under the present system, according to medical experts. "It is simply not possible to identify all the adverse effects of drugs before they are marketed", say three physicians writing in the New England Journal of Medicine. In fact, "Overall, 51% of approved drugs have serious side effects not detected prior to approval".
Side effects cannot be anticipated for two main reasons: (1) individuals vary greatly in their reactions to chemical substances; and (2) rare side effects may not appear in a small test group but may become painfully obvious when millions of people start taking the drug.
Even a few years ago, drugs reached a mass audience slowly, providing time for unexpected side effects to show up in relatively small numbers of people. But today drugs are marketed directly to consumers via TV, so a huge market can be created quickly, and side effects can appear in large numbers of people.
The sexual potency drug Viagra provides an example. Within a few months of its introduction, several million people began taking Viagra, and many serious side effects, including fatalities, suddenly appeared.
Despite the widespread knowledge that half of all new drugs will cause serious side effects in some people, neither the government nor the drug companies systematically collect information on adverse reactions to new drugs. "Even when it is recognized that a new drug will be given to many patients for many years, rarely are systematic post-marketing studies carried out", according to the New England Journal of Medicine article.
In the US, there is no formal procedure for monitoring drug safety. If physicians became aware that a new drug has killed or maimed one of their patients, or caused an allergic reaction, they may report it, but they also may not.
As reports filter into the US Food and Drug Administration (FDA) in hit-or-miss fashion, FDA can revoke the approval of a drug, and sometimes does, but almost never quickly.
In December 1997, the popular non-sedating antihistamine terfenadine was withdrawn because a safer alternative existed without terfenadine's danger of a potentially fatal heart arrhythmia (irregular heart beat). By that time terfenadine had been on the market 12 years.
Last September the FDA took the diet drugs fenfluramine and dexfenfluramine off the market because of heart valve damage to 31% of those who took the drugs in combination with another diet pill, phentermine (a combination known as fen/phen). Fenfluramine could also damage heart valves when taken alone. By the time fenfluramine was banned, it had been on the market for 24 years.
No second opinion
The three doctors published in the New England Journal of Medicine contrasted prescription drug safety with airline safety.
Airplanes are built, licensed and flown according to standards set by the Federal Aviation Administration (FAA). But whenever a plane crash occurs, a different agency steps in to establish the facts and make recommendations for avoiding future crashes. The assumption is that a second, independent, agency is needed because the FAA would have a conflict of interest investigating crashes of planes it had approved and licensed.
In drug safety, there is only one agency. The FDA approves pharmaceuticals and also has responsibility for investigating injuries and deaths caused by those pharmaceuticals. FDA has a very limited capacity to conduct surveillance studies so, in fact, it relies on the drug companies to provide data on deaths and illnesses caused by their own products.
When the FDA learned that dexfenfluramine was dangerous, the agency had no good data on the total number of people harmed. At the time, the director of FDA's Office of Epidemiology and Biostatistics said, defensively, "We've done what is necessary to determine there is a problem. Other information is up to American Home Products [which marketed dexfenfluramine] to find out."
Of course, American Home Products had little incentive to investigate the number of problems caused by its product.
The three doctors say an independent drug safety board is needed to study deaths and illnesses from drugs. They point out that FDA officials spend up to a year evaluating a drug before approving it for marketing, "and it is unlikely that those who recommended a drug for approval could later conduct a dispassionate evaluation of possible harm due to that drug".
Recommendations
According to a recent commentary in the Journal of the American Medical Association, a competent drug safety program would have four parts:
(1) A program to monitor all adverse effects from prescription drugs and annually report the number of injuries and deaths and their likely causes. Currently no-one keeps such statistics.
(2) A program to monitor side effects from new drugs. Presently, the FDA's Division of Pharmacovigilance and Epidemiology (DPE) has a staff of 52 people, but only eight of those have MD degrees, and only one has a PhD in epidemiology. This small group collects anecdotal information about side effects of new drugs, but hasn't the resources to be systematic or thorough.
The problem with anecdotal information is that only about 1% of adverse drug reactions get reported in this way. For example, the FDA received an average of 82 reports each year about adverse reactions caused by the drug digoxin. This relatively small number of reports seemed to indicate that digoxin was not a big problem. However, a systematic survey of Medicare records revealed 202,211 hospitalisations for adverse reactions to digoxin during a seven-year period.
When FDA's DPE identifies a drug problem, it can only pass the information along to the division of FDA that approved the drug. That division can require the manufacturer to develop additional information. However, "The most common corrective action is a change in the product disclosure label or package insert".
(3) A program to make sure that safety information is being disseminated and heeded by physicians. FDA currently has no such program. "The limited information available, however, suggests that some important safety information — such as boxed warnings on drug disclosure labels — either was not received or had little effect".
(4) A program to seek out aggressively information about unsuspected adverse reactions to drugs, instead of waiting passively for anecdotal information to filter in.
The present Congress has recently diminished the powers of the FDA to monitor drug safety. Congress now allows drug companies to pay fees which FDA uses to speed up the approval process for new drugs. As a result, during 1996-1997, FDA approved 92 new drugs for market — twice the previous rate. However, Congress specifically prohibited FDA from using any of the new money for monitoring drug safety.
[From Rachel's Environment & Health Weekly. Like Green Left Weekly, Rachel's is a non-profit publication which distributes information without charge on the internet and depends on the generosity of readers to survive. If you are able to help keep this valuable resource in existence, send your contribution to Environmental Research Foundation, PO Box 5036, Annapolis, Maryland 21403-7036, USA. In the United States, donations to ERF are tax deductible.]