THE FIRST IATROGENIC STUDY

Dr. Lucian L. Leape opened medicine's Pandora's box in his 1994 paper, “Error in Medicine,” which appeared in the Journal of the American Medical Association (JAMA).(16) He found that Schimmel reported in 1964 that 20% of hospital patients suffered iatrogenic injury, with a 20% fatality rate. In 1981 Steel reported that 36% of hospitalized patients experienced iatrogenesis with a 25% fatality rate, and adverse drug reactions were involved in 50% of the injuries. In 1991, Bedell reported that 64% of acute heart attacks in one hospital were preventable and were mostly due to adverse drug reactions.

Leape focused on the “Harvard Medical Practice Study” published in 1991, (16a) which found a 4% iatrogenic injury rate for patients, with a 14% fatality rate, in 1984 in New York State. From the 98,609 patients injured and the 14% fatality rate, he estimated that in the entire U.S. 180,000 people die each year partly as a result of iatrogenic injury.

Why Leape chose to use the much lower figure of 4% injury for his analysis remains in question. Using instead the average of the rates found in the three studies he cites (36%, 20%, and 4%) would have produced a 20% medical error rate. The number of iatrogenic deaths using an average rate of injury and his 14% fatality rate would be 1,189,576.

Leape acknowledged that the literature on medical errors is sparse and represents only the tip of the iceberg, noting that when errors are specifically sought out, reported rates are “distressingly high.” He cited several autopsy studies with rates as high as 35-40% of missed diagnoses causing death. He also noted that an intensive care unit reported an average of 1.7 errors per day per patient, and 29% of those errors were potentially serious or fatal.

Leape calculated the error rate in the intensive care unit study. First, he found that each patient had an average of 178 “activities” (staff/procedure/medical interactions) a day, of which 1.7 were errors, which means a 1% failure rate. This may not seem like much, but Leape cited industry standards showing that in aviation, a 0.1% failure rate would mean two unsafe plane landings per day at Chicago's O'Hare International Airport; in the US Postal Service, a 0.1% failure rate would mean 16,000 pieces of lost mail every hour; and in the banking industry, a 0.1% failure rate would mean 32,000 bank checks deducted from the wrong bank account.

In trying to determine why there are so many medical errors, Leape acknowledged the lack of reporting of medical errors. Medical errors occur in thousands of different locations and are perceived as isolated and unusual events. But the most important reason that the problem of medical errors is unrecognized and growing, according to Leape, is that doctors and nurses are unequipped to deal with human error because of the culture of medical training and practice. Doctors are taught that mistakes are unacceptable. Medical mistakes are therefore viewed as a failure of character and any error equals negligence. No one is taught what to do when medical errors do occur. Leape cites McIntyre and Popper, who said the “infallibility model” of medicine leads to intellectual dishonesty with a need to cover up mistakes rather than admit them. There are no Grand Rounds on medical errors, no sharing of failures among doctors, and no one to support them emotionally when their error harms a patient.

Leape hoped his paper would encourage medical practitioners “to fundamentally change the way they think about errors and why they occur.” It has been almost a decade since this groundbreaking work, but the mistakes continue to soar.

In 1995, a JAMA report noted, "Over a million patients are injured in US hospitals each year, and approximately 280,000 die annually as a result of these injuries. Therefore, the iatrogenic death rate dwarfs the annual automobile accident mortality rate of 45,000 and accounts for more deaths than all other accidents combined."(23)

At a 1997 press conference, Leape released a nationwide poll on patient iatrogenesis conducted by the National Patient Safety Foundation (NPSF), which is sponsored by the American Medical Association (AMA). Leape is a founding member of NPSF. The survey found that more than 100 million Americans have been affected directly or indirectly by a medical mistake. Forty-two percent were affected directly and 84% personally knew of someone who had experienced a medical mistake.(14)

At this press conference, Leape updated his 1994 statistics, noting that as of 1997, medical errors in inpatient hospital settings nationwide could be as high as 3 million and could cost as much as $200 billion . Leape used a 14% fatality rate to determine a medical error death rate of 180,000 in 1994.(16) In 1997, using Leape's base number of 3 million errors, the annual death rate could be as high as 420,000 for hospital inpatients alone.

ONLY A FRACTION OF MEDICAL ERRORS ARE REPORTED

In 1994, Leape said he was well aware that medical errors were not being reported.(16) A study conducted in two obstetrical units in the UK found that only about one-quarter of adverse incidents were ever reported, to protect staff, preserve reputations, or for fear of reprisals, including lawsuits.(24). An analysis by Wald and Shojania found that only 1.5% of all adverse events result in an incident report, and only 6% of adverse drug events are identified properly. The authors learned that the American College of Surgeons estimates that surgical incident reports routinely capture only 5-30% of adverse events. In one study, only 20% of surgical complications resulted in discussion at morbidity and mortality rounds.(25) From these studies, it appears that all the statistics gathered on medical errors may substantially underestimate the number of adverse drug and medical therapy incidents. They also suggest that our statistics concerning mortality resulting from medical errors may be in fact be conservative figures.

An article in Psychiatric Times (April 2000) outlines the stakes involved in reporting medical errors.(26) The authors found that the public is fearful of suffering a fatal medical error, and doctors are afraid they will be sued if they report an error. This brings up the obvious question: who is reporting medical errors? Usually it is the patient or the patient's surviving family. If no one notices the error, it is never reported. Janet Heinrich, an associate director at the U.S. General Accounting Office responsible for health financing and public health issues, testified before a House subcommittee hearing on medical errors that "the full magnitude of their threat to the American public is unknown” and "gathering valid and useful information about adverse events is extremely difficult." She acknowledged that the fear of being blamed, and the potential for legal liability, played key roles in the underreporting of errors. The Psychiatric Times noted that the AMA strongly opposes mandatory reporting of medical errors.(26) If doctors are not reporting, what about nurses? A survey of nurses found that they also fail to report medical mistakes for fear of retaliation.(27)

Standard medical pharmacology texts admit that relatively few doctors ever report adverse drug reactions to the FDA.(28) The reasons range from not knowing such a reporting system exists to fear of being sued.(29) Yet the public depends on this tremendously flawed system of voluntary reporting by doctors to know whether a drug or a medical intervention is harmful.

Pharmacology texts also will tell doctors how hard it is to separate drug side effects from disease symptoms. Treatment failure is most often attributed to the disease and not the drug or doctor. Doctors are warned, “Probably nowhere else in professional life are mistakes so easily hidden, even from ourselves.”(30) It may be hard to accept, but it is not difficult to understand why only 1 in 20 side effects is reported to either hospital administrators or the FDA.(31, 31a)

If hospitals admitted to the actual number of errors for which they are responsible, which is about 20 times what is reported, they would come under intense scrutiny.(32) Jerry Phillips, associate director of the FDA's Office of Post Marketing Drug Risk Assessment, confirms this number. “In the broader area of adverse drug reaction data, the 250,000 reports received annually probably represent only 5% of the actual reactions that occur.”(33) Dr. Jay Cohen, who has extensively researched adverse drug reactions, notes that because only 5% of adverse drug reactions are reported, there are in fact 5 million medication reactions each year.(34)

A 2003 survey is all the more distressing because there seems to be no improvement in error reporting, even with all the attention given to this topic. Dr. Dorothea Wild surveyed medical residents at a community hospital in Connecticut and found that only half were aware that the hospital had a medical error-reporting system, and that the vast majority did not use it at all. Dr. Wild says this does not bode well for the future. If doctors don't learn error reporting in their training, they will never use it. Wild adds that error reporting is the first step in locating the gaps in the medical system and fixing them. Not even that first step has been taken to date.(35)

PUBLIC SUGGESTIONS ON IATROGENESIS

In a telephone survey, 1,207 adults ranked the effectiveness of the following measures in reducing preventable medical errors that result in serious harm.(36) (Following each measure is the percentage of respondents who ranked the measure as “very effective.”)

• giving doctors more time to spend with patients (78%)
• requiring hospitals to develop systems to avoid medical errors (74%)
• better training of health professionals (73%)
• using only doctors specially trained in intensive care medicine on intensive care units (73%)
• requiring hospitals to report all serious medical errors to a state agency (71%)
• increasing the number of hospital nurses (69%)
• reducing the work hours of doctors in training to avoid fatigue (66%)
• encouraging hospitals to voluntarily report serious medical errors to a state agency (62%).

DRUG IATROGENESIS

Prescription drugs constitute the major treatment modality of scientific medicine. With the discovery of the “germ theory,” medical scientists convinced the public that infectious organisms were the cause of illness. Finding the “cure” for these infections proved much harder than anyone imagined. From the beginning, chemical drugs promised much more than they delivered. But far beyond not working, the drugs also caused incalculable side effects. The drugs themselves, even when properly prescribed, have side effects that can be fatal, as Lazarou's study(1) showed. But human error can make the situation even worse.

Medication Errors

A survey of a 1992 national pharmacy database found a total of 429,827 medication errors from 1,081 hospitals. Medication errors occurred in 5.22% of patients admitted to these hospitals each year. The authors concluded that at least 90,895 patients annually were harmed by medication errors in the US as a whole.(37)

A 2002 study shows that 20% of hospital medications for patients had dosage errors. Nearly 40% of these errors were considered potentially harmful to the patient. In a typical 300-patient hospital, the number of errors per day was 40.(38)

Problems involving patients' medications were even higher the following year. The error rate intercepted by pharmacists in this study was 24%, making the potential minimum number of patients harmed by prescription drugs 417,908.(39)

More-recent studies on adverse drug reactions show that the figures from 1994 published in Lazarou's 1998 JAMA article may be increasing. A 2003 study followed 400 patients after discharge from a tertiary care hospital setting (requiring highly specialized skills, technology, or support services). Seventy-six patients (19%) had adverse events. Adverse drug events were the most common, at 66% of all events. The next most common event was procedure-related injuries, at 17%.(40)

In a New England Journal of Medicine study, an alarming one in four patients suffered observable side effects from the more than 3.34 billion prescription drugs filled in 2002.(41) One of the doctors who produced the study was interviewed by Reuters and commented, "With these 10-minute appointments, it's hard for the doctor to get into whether the symptoms are bothering the patients."(42) William Tierney, who editorialized on the New England Journal study, said “… given the increasing number of powerful drugs available to care for the aging population, the problem will only get worse.” The drugs with the worst record of side effects were selective serotonin reuptake inhibitors ( SSRIs), nonsteroidal anti-inflammatory drugs (NSAIDs), and calcium-channel blockers. Reuters also reported that prior research has suggested that nearly 5% of hospital admissions (over 1 million per year) are the result of drug side effects. But most of the cases are not documented as such. The study found that one of the reasons for this failure is that in nearly two-thirds of the cases, doctors could not diagnose drug side effects or the side effects persisted because the doctor failed to heed the warning signs.

Patients seeking a more joyful existence and relief from worry, stress, and anxiety often fall victim to the messages endlessly displayed on TV and billboards. Often, instead of gaining relief, they fall victim to the myriad iatrogenic side effects of antidepressant medication.

Moreover, a whole generation of antidepressant users has been created from young people growing up on Ritalin. Medicating youth and modifying their emotions must have some impact on how they learn to deal with their feelings. They learn to equate coping with drugs rather than with their inner resources. As adults, these medicated youth reach for alcohol, drugs, or even street drugs to cope. According to JAMA , “Ritalin acts much like cocaine.”(43) Today's marketing of mood-modifying drugs such as Prozac and Zoloft ® makes them not only socially acceptable but almost a necessity in today's stressful world.

To reach the widest audience possible, drug companies are no longer just targeting medical doctors with their marketing of antidepressants. By 1995, drug companies had tripled the amount of money allotted to direct advertising of prescription drugs to consumers. The majority of this money is spent on seductive television ads. From 1996 to 2000, spending rose from $791 million to nearly $2.5 billion.(44) This $2.5 billion represents only 15% of the total pharmaceutical advertising budget. While the drug companies maintain that direct-to-consumer advertising is educational, Dr. Sidney M. Wolfe of the Public Citizen Health Research Group in Washington, DC, argues that the public often is misinformed about these ads.(45) People want what they see on television and are told to go to their doctors for a prescription. Doctors in private practice either acquiesce to their patients' demands for these drugs or spend valuable time trying to talk patients out of unnecessary drugs. Dr. Wolfe remarks that one important study found that people mistakenly believe that the “FDA reviews all ads before they are released and allows only the safest and most effective drugs to be promoted directly to the public.”(46)

How Do We Know Drugs Are Safe?

Another aspect of scientific medicine that the public takes for granted is the testing of new drugs. Drugs generally are tested on individuals who are fairly healthy and not on other medications that could interfere with findings. But when these new drugs are declared “safe” and enter the drug prescription books, they are naturally going to be used by people who are on a variety of other medications and have a lot of other health problems. Then a new phase of drug testing called “post-approval” comes into play, which is the documentation of side effects once drugs hit the market. In one very telling report, the federal government's General Accounting Office "found that of the 198 drugs approved by the FDA between 1976 and 1985... 102 (or 51.5%) had serious post-approval risks... the serious post-approval risks (included) heart failure, myocardial infarction, anaphylaxis, respiratory depression and arrest, seizures, kidney and liver failure, severe blood disorders, birth defects and fetal toxicity, and blindness."(47)

NBC Television's investigative show “Dateline” wondered if your doctor is moonlighting as a drug company representative. After a yearlong investigation, NBC reported that because doctors can legally prescribe any drug to any patient for any condition, drug companies heavily promote "off label" and frequently inappropriate and untested uses of these medications, even though these drugs are approved only for the specific indications for which they have been tested.(48)

The leading causes of adverse drug reactions are antibiotics (17%), cardiovascular drugs (17%), chemotherapy (15%), and analgesics and anti-inflammatory agents (15%).(49)

Specific Drug Iatrogenesis: Antibiotics

According to William Agger, MD, director of microbiology and chief of infectious disease at Gundersen Lutheran Medical Center in La Crosse, WI, 30 million pounds of antibiotics are used in America each year.(50) Of this amount, 25 million pounds are used in animal husbandry, and 23 million pounds are used to try to prevent disease and the stress of shipping, as well as to promote growth. Only 2 million pounds are given for specific animal infections. Dr. Agger reminds us that low concentrations of antibiotics are measurable in many of our foods and in various waterways around the world, much of it seeping in from animal farms.

Agger contends that overuse of antibiotics results in food-borne infections resistant to antibiotics. Salmonella is found in 20% of ground meat, but the constant exposure of cattle to antibiotics has made 84% of salmonella resistant to at least one anti-salmonella antibiotic. Diseased animal food accounts for 80% of salmonellosis in humans, or 1.4 million cases per year. The conventional approach to countering this epidemic is to radiate food to try to kill all organisms while continuing to use the antibiotics that created the problem in the first place. Approximately 20% of chickens are contaminated with Campylobacter jejuni, an organism that causes 2.4 million cases of illness annually. Fifty-four percent of these organisms are resistant to at least one anti-campylobacter antimicrobial agent.

Denmark banned growth-promoting antibiotics beginning in 1999, which cut their use by more than half within a year, from 453,200 to 195,800 pounds. A report from Scandinavia found that removing antibiotic growth promoters had no or minimal effect on food production costs. Agger warns that the current crowded, unsanitary methods of animal farming in the US support constant stress and infection, and are geared toward high antibiotic use.

In the US, over 3 million pounds of antibiotics are used every year on humans. With a population of 284 million Americans, this amount is enough to give every man, woman, and child 10 teaspoons of pure antibiotics per year. Agger says that exposure to a steady stream of antibiotics has altered pathogens such as Streptococcus pneumoniae, Staplococcus aureus, and entercocci, to name a few.

Almost half of patients with upper respiratory tract infections in the U.S. still receive antibiotics from their doctor.(51) According to the CDC, 90% of upper respiratory infections are viral and should not be treated with antibiotics. In Germany, the prevalence of systemic antibiotic use in children aged 0-6 years was 42.9%.(52)

Data obtained from nine US health insurers on antibiotic use in 25,000 children from 1996 to 2000 found that rates of antibiotic use decreased. Antibiotic use in children aged three months to under 3 years decreased 24%, from 2.46 to 1.89 antibiotic prescriptions per patient per year. For children aged 3 to under 6 years, there was a 25% reduction from 1.47 to 1.09 antibiotic prescriptions per patient per year. And for children aged 6 to under 18 years, there was a 16% reduction from 0.85 to 0.69 antibiotic prescriptions per patient per year.(53) Despite these reductions, the data indicate that on average every child in America receives 1.22 antibiotic prescriptions annually.

Group A beta-hemolytic streptococci is the only common cause of sore throat that requires antibiotics, with penicillin and erythromycin the only recommended treatment. Ninety percent of sore-throat cases, however, are viral. Antibiotics were used in 73% of the estimated 6.7 million adult annual visits for sore throat in the US between 1989 and 1999. Furthermore, patients treated with antibiotics were prescribed non-recommended broad-spectrum antibiotics in 68% of visits. This period saw a significant increase in the use of newer, more expensive broad-spectrum antibiotics and a decrease in use of the recommended antibiotics penicillin and erythromycin.(54) Antibiotics being prescribed in 73% of sore-throat cases instead of the recommended 10% resulted in a total of 4.2 million unnecessary antibiotic prescriptions from 1989 to 1999.

The Problem with Antibiotics

In September 2003, the CDC re-launched a program started in 1995 called “Get Smart: Know When Antibiotics Work.”(55) This $1.6 million campaign is designed to educate patients about the overuse and inappropriate use of antibiotics. Most people involved with alternative medicine have known about the dangers of antibiotic overuse for decades. Finally the government is focusing on the problem, yet it is spending only a miniscule amount of money on an iatrogenic epidemic that is costing billions of dollars and thousands of lives. The CDC warns that 90% of upper respiratory infections, including children's ear infections, are viral and that antibiotics do not treat viral infection. More than 40% of about 50 million prescriptions for antibiotics written each year in physicians' offices are inappropriate.(2) Using antibiotics when not needed can lead to the development of deadly strains of bacteria that are resistant to drugs and cause more than 88,000 deaths due to hospital-acquired infections.(9) The CDC, however, seems to be blaming patients for misusing antibiotics even though they are available only by prescription from physicians. According to Dr. Richard Besser, head of “Get Smart”: "Programs that have just targeted physicians have not worked. Direct-to-consumer advertising of drugs is to blame in some cases.” Besser says the program “teaches patients and the general public that antibiotics are precious resources that must be used correctly if we want to have them around when we need them. Hopefully, as a result of this campaign, patients will feel more comfortable asking their doctors for the best care for their illnesses, rather than asking for antibiotics."(56)