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What Is the Real World Incidence of Drug Side Effects?

There are many reasons why clinical trials don't reveal the true incidence of drug side effects in the real world.
What Is the Real World Incidence of Drug Side Effects?
Magnified focal area over the warning information of a prescription medication

I do not believe that anyone really knows how often drug side effects occur in the real world. That includes the drug companies, the FDA, physicians and pharmacists. And I don’t believe that these groups really want to know.

This is an excerpt from Dennis Miller’s explosive new book The Shocking Truth About Pharmacy: A Pharmacist Reveals All The Disturbing Secrets. The entire book is available for download from Amazon for 99 cents.

Side Effects Occur in Just One Patient Out of a Million?

Many pharmacists are probably familiar with this scenario. When we fill prescriptions, our printer prints a specific leaflet for each drug we dispense. Say a customer has three prescriptions filled. The printer will print a leaflet for each drug and thus the patient will receive three separate leaflets.

Very often when the subjects of drug leaflets and drug side effects come up, customers say something like, “Yeah. The side effect occurs in one person in a million so the FDA requires it to be listed. I usually throw away those drug leaflets as soon as I get home.”

When confronted with that attitude from customers, I usually say to myself that throwing away the drug leaflets is not a smart thing to do. Why would our customers not want to learn as much as possible about each prescription drug they receive?

I believe that the one-in-a-million concept as regards the frequency of drug side effects is widespread. Pharma is in no hurry to correct this fundamental misconception about side effects. The reality is that the “one-in-a-million” concept is totally bogus and extremely optimistic because the true incidence of side effects varies widely depending on the drug, the patient and the medical source consulted.

The True Incidence of Side Effects Is Hard to Determine:

The true incidence of side effects is a hotly debated topic among drug experts. The incidence of side effects seen during company-sponsored drug trials and reported to the FDA are very often significantly lower than physicians see in the real world (once a drug has been approved and is widely prescribed).

In my opinion, the reality is that the FDA doesn’t really know the true incidence of adverse effects with the drugs it approves, i.e., how often side effects occur in the real world. This includes potentially serious side effects with commonly prescribed drugs like cholesterol-lowering statins, proton pump inhibitors, and antibiotics such as clindamycin and fluoroquinolones. The FDA typically relies on adverse effect data submitted by the drug sponsor.

People hear the long lists of scary side effects at the end of drug commercials on television, but this doesn’t seem to dampen their enthusiasm for pharmaceuticals. Perhaps users of prescription drugs want to believe that side effects are rare because they want to believe that quick-fix pills are a reasonable solution for every ill.

Somehow a large segment of the population seems to believe that the pharmaceutical industry is magically capable of developing drugs so that each of the 50 to 200 side effects listed in the official prescribing information will occur at a frequency of one in a million users.

The public does not seem to know that the FDA relies on data submitted by drug companies. Clearly the drug companies have a tremendous incentive to exaggerate the benefits of drugs and to downplay their risks. Do you really believe that the drug companies are entirely truthful and transparent in the data that they submit to the FDA about drug safety?

Can we believe the FDA’s assurances of safety? Can we believe what Big Pharma says about the incidence of side effects? Can we believe that physicians are well aware of all the side effects associated with all the drugs they prescribe? Do busy physicians essentially believe that if a drug is still on the market then the FDA feels it is safe? Do physicians too often dismiss patient complaints about side effects?

Should You Trust the Results of Studies Sponsored by Pharma Regarding Drug Safety and Effectiveness?

Marcia Angell, MD, was formerly the editor-in-chief at The New England Journal of Medicine.

In her highly acclaimed book The Truth About The Drug Companies, Angell writes (p. xviii-xix):

“I witnessed firsthand the influence of the industry on medical research during my decades at The New England Journal of Medicine. The staple of the journal is research about causes of and treatments for disease. Increasingly, this work is sponsored by drug companies. I saw companies begin to exercise a level of control over the way research is done that was unheard of when I first came to the journal, and the aim was clearly to load the dice to make sure their drugs looked good. As an example, companies would require researchers to compare a new drug with a placebo (sugar pill) instead of with an older drug. That way, the new drug would look good even though it might actually be worse than the older one. …As I saw industry influence grow, I became increasingly troubled by the possibility that much published research is seriously flawed, leading doctors to believe new drugs are generally more effective and safer than they actually are.”

What Is the Real World Incidence of Statin Side Effects?

Here is a letter to BMJ stating that the true incidence of statin side effects is important to determine given the fact that this class of drugs is so widely prescribed.

(Azeem Majeed, Mariam Molokhia, “Urgent need to establish the true incidence of the side effects of statins,” BMJ 2014;348:g3650)

“One key area of the debate about widening the use of statins is the discordance between rates of side effects of statins in clinical trials and in clinical practice. In clinical trials, the incidence of side effects from statins is low and similar in the intervention and placebo groups. By contrast, observational studies using primary care databases report a much higher rate of potentially serious side effects (such as myopathy and renal failure) in people taking statins. Even these rates derived from clinical records may underestimate the true incidence of side effects in people taking statins, because not all patients with side effects inform their doctor and not all doctors enter a relevant diagnostic code in the patient’s electronic medical record.

“Many GPs will be familiar with patients who report side effects after starting statins. These side effects are often severe enough for patients to stop taking the drug.

}…we urgently need to establish the true incidence of the side effects of statins if doctors and patients are to be encouraged to increase the use of these drugs, particularly in people with lower levels of cardiovascular risk.”

Physicians are often openly hostile and dismissive toward patients’ concerns about drug adverse effects. I have a neighbor who has taken statins for several years and developed a serious neurological disorder. There is a growing medical literature about a possible link between statins and symptoms that resemble Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig’s disease). For that reason, I sent an e-mail to Beatrice Golomb, MD, PhD, who has studied statin side effects extensively. She is a nationally recognized expert on that subject.

In answering my question regarding whether there is a possible link between statins and neurological disorders, Dr. Golomb explained the strong tendency of physicians to downplay side effects in general (personal communication, April 11, 2019):

“Since much of medical education is pharma funded, as are most researchers who study drugs, there is very poor attention to and awareness of adverse effects in general, and many physicians’ attitudes toward adverse effects can be frankly hostile. We have had patients tell us that even when they come armed with papers documenting a problem, the doctors will dismiss the problem, say they have not heard of it so it cannot be true, or claim that because it is rare, it cannot be operating in them.”

Are Human Research Subjects in Drug Trials Subtly Pressured to Minimize Side Effects?

In his highly acclaimed book Bitter Pills (New York: Bantam, 1998, pp. 258-9), investigative journalist Stephen Fried discusses the subtle yet powerful pressure placed by pharmaceutical companies on the human subjects who are paid to participate in drug trials. Fried says he spent “an eye-opening evening with a group of human drug research subjects, or ‘guinea pigs’ as they prefer to be called, who lay their able bodies on the line (for $200 a day) to safety test drugs at clinical research centers in and around Philadelphia.”

He describes what those research subjects “had to say about the information collected, or not collected, in the trials themselves.”

“Scott, a twenty-five-year-old who moved from Minnesota to Philadelphia in part because it was such a Pharma Belt mecca for guinea pigs, was appalled at the casual way test results were elicited from subjects. “It’s unscientific to the point of being buffoonery, sometimes,” he said. “It reminds me of an eighth-grade science experiment: here are the variables, keep it simple and clean, and these are the results you need to get a good grade. And to get things to work out, if you have to kind of flub some things, that’s okay.

“For example, I was in a study for a sleeping pill. Before it started, they brought us all together, and the doctor came out and talked to us. She said, “This is the second time we’ve tried this pill in humans. It’s very safe. Now if you look right here in the protocol [the detailed description of the trial given to the subjects], it says some people in the first trial were seeing things.” And then she said, “But these people, they hadn’t been honest with us about whether they’d had mental problems before in their lives. So if you don’t have psychological problems, you won’t be seeing anything.” I found out later that three-quarters of the study participants had seen things. But what she’s doing, you see, is implanting the idea in your head that if you’re seeing things, it means you have psychological problems. …It’s such a simplistic and mechanical way these doctors look at health. And from the beginning they’re guiding how you’re going to respond to the study and how they’re going to report it.

“Jamie, also in his mid-twenties, saw other biases as well. “First of all,” he explained, “If you’re a person who does drug studies, you are generally someone who is fairly resistant to drugs and don’t feel the bad effects of them very easily. If you did have strong reactions, the lab would stop wanting to use you–and that happens–or you would decide you didn’t want to do the studies.”

“But Jamie has also seen some of his reactions not get reported. “If you tell them you’re a little tired or have a headache,” he said, “unless you tell them several times, they often don’t write it down. I’ve looked in my book [the diary kept on each patient], and they didn’t write it down.

“Look, you’ve got a researcher who wants to pass a drug through the study, and you have a volunteer who wants to be in the study and wants to get into other studies in the future. And I’ll tell you, I’ve been given hints about being a good guinea pig. The nurse comes up and asks, ‘You’re not suffering any side effects, are you?’ and she’ll be shaking her head no. ‘You’re not feeling headachy or anything like that, are you?’ and she’ll be shaking her head no. ‘Okay, so you’re feeling fine?’ and she’s nodding yes.

“Scott said he thought they wouldn’t overlook a massive problem, but “they’re willing to sweep little problems under the bed. It’s not as scientific as it’s presented to the public. I think it could be more scientific, but they’d have to remove certain external factors. Like the greed motive.”

The drug industry has created a carnival atmosphere through rosy drug advertisements to promote the use of pharmaceuticals. Does anyone believe that such a deceptive industry whose commercials utilize such things as a turkey (advertisement for Chantix for smoking cessation) or a talking owl (advertisement for Xyzal for allergy symptoms) feels any obligation to submit truthful data to the FDA about the true incidence of adverse effects? In an industry that routinely exaggerates the benefits of its products and downplays the risks, and that engages in price gouging when then are no or few competitive products, does anyone believe that such an industry feels obligated to submit fully transparent data to the FDA about the safety and effectiveness of its products?

Clinical Trials Do Not Represent the Real World:

Should you trust the results of studies of drug safety and effectiveness sponsored by Pharma? Drug studies are typically conducted using subjects (often paid volunteers or prison inmates) who are much healthier and younger than the target population for these drugs in the real world. In drug trials, concomitant diseases are viewed as complicating factors whereas, in the real world, the people for whom these drugs are prescribed very often have multiple conditions. Drug studies routinely compare Drug A to placebo. Why not compare Drug A to Drug B? Why not compare Drug A to lifestyle changes, dietary changes, exercise and weight loss

The “Honor System” with Clinical Trials Is Not Working:

The FDA relies on drug companies to submit truthful data about the safety and effectiveness of drugs. Most people do not seem to know that the FDA does not actually conduct clinical trials. The FDA merely approves the design of the trials and then examines the data submitted by drug companies. Clearly the drug companies have a huge financial incentive to exaggerate the benefits of drugs and to downplay the risks. The “honor system” is inadequate for assessing the safety and effectiveness of drugs.

The FDA’s Definition of “Safe and Effective” Is Far Different from the Layman’s Definition:

The FDA’s definition of “safe and effective” conflicts fundamentally with the layman’s definition of these two words. Most drugs come with a long list of potential side effects. This indicates that most drugs are crude synthetic substances, never before seen in the long course of human evolution, that overwhelm delicate biological processes which have been fine tuned over the millennia. Consider, for example, the fact that many commonly prescribed drugs are linked to tumors in lab animals and, in some cases, in humans.

When the FDA withdraws drugs from the market, this should cause the public to wonder how well the FDA actually understands the drugs that it approves. But the public remains largely optimistic about taking pills. See, for example, Too Many Pills: How Too Much Medicine Is Endangering Our Health And What We Can Do About It (James Le Fanu, M.D., Little, Brown, 2018)

So-called “Clean” Drugs Don’t Seem to be So Clean After All:

In pharmacy school, some professors would describe a new drug as “clean,” meaning that it had few side effects. So when I actually saw a copy of the official prescribing information (the official label), I assumed that I would see a very short list of possible side effects. But that never happened. When I finally saw the official label, the drug that our professors had described as “clean” had just as many possible side effects as most of the other drugs in the Physicians’ Desk Reference. I’m still awaiting the arrival of a new drug that fits my professors’ descriptions of “clean,” likely meaning that it has fewer than a couple dozen potential side effects listed in the official prescribing information.

How can one listen to drug advertisements on TV and conclude that those drugs are “clean,” and that they are ideal ways to approach human illness? In general, a good solution to any problem in life has very few adverse consequences. Using that criteria, an exclusive focus on pharmaceuticals cannot be seen as an ideal way to construct a health care system. Fruits, vegetables and exercise clearly have far fewer adverse effects than pharmaceuticals.

“Side” Effects vs. “Untoward” Effects:

Drugs are said to have “side effects” or “adverse effects.” A more accurate term is “untoward effects.” Each drug has many actions across different systems in the body. The effects that the drug has on the target organ or biological process are the drug’s intended effects. But the many other effects are not anomalies and they should not be surprising, because those other effects are, in fact, the innate biological actions of the drug. Drugs have immutable characteristics. Pharma conveniently labels the unwanted effects as “side effects,” “adverse effects,” or “drug misadventures” when, in fact, the drugs possess both intended and unintended effects.

Do Patients Discuss Side Effects with Pharmacists More Often Than with Physicians?

Are patients more likely to ask a pharmacist (rather than a physician) whether symptoms they’re experiencing can be a side effect of a drug? Are patients sometimes reluctant to question doctors about such symptoms because the patients fear that the physician will view it as criticizing his/her prescribing decision (choice of drug)?

Are Lists of Side Effects So Lengthy Just to Protect Pharma from Lawsuits?

Do drug companies list every conceivable side effect in the official prescribing information to protect themselves from a lawsuit? Drug companies perhaps believe that it is better to disclose a suspected side effect (no matter how mild or serious) because it is better to disclose it in the label than know about it and hide it.

If that is the case, the official label is akin to a data dump intended to protect drug companies from lawsuits. It would be much more helpful if Pharma would report truthful data about the incidence of drug side effects seen in drug trials. Critics of Pharma sometimes say that the official prescribing information is more like a legal document intended for lawyers than a medical document intended to assist physicians in prescribing drugs.

Is Pharma Guilty of Extreme Hubris?

Pharmaceutical industry scientists seem to act as though they know more than Mother Nature. The huge number of side effects tells me that these Pharma researchers are tinkering around in complex biological processes about which they know very little. But that does not seem to cause them to have a humble attitude toward intervening with crude synthetic chemicals in infinitely complex and wondrous biological processes that have been fine-tuned over hundreds of thousands of years.

In Conclusion:

One wonders about the truthfulness of drug trials sponsored by the drug companies. One reads that volunteers in drug trials know that the investigators don’t want long lists of side effects. One reads about pressure by drug companies on the FDA to speed approval of drugs. One wonders why the public remains so enthusiastic about pharmaceuticals given, for example, the long lists of potential side effects at the end of drug advertisements on television. One wonders why the public doesn’t re-double their efforts to prevent disease so that pills are not necessary.

This is an excerpt from Dennis Miller’s explosive new book The Shocking Truth About Pharmacy: A Pharmacist Reveals All The Disturbing Secrets. The entire book is available for download from Amazon for 99 cents.

https://www.amazon.com/dp/B08GL5354F/ref=rdr_kindle_ext_tmb

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