You probably assume that your doctor is fully informed about the medicines she prescribes. In theory, she should know exactly how safe and effective the drugs she prescribes are. In truth, this information is surprisingly hard to find. Physicians, pharmacists, nurse practitioners and patients have no easy way to discover quantitative information about side effects or benefits. You can learn more about the pros and cons of a television or a toaster than you can about the pills you swallow every morning.
Making Informed Decisions:
How do you decide what cell phone, car or laptop to purchase? Most people realize that they’ll make a better decision if they have some data. Many search online reviews.
Others choose an objective resource such as Consumer Reports (CR). If the testers provide scores on a vehicle, lawn mower or dishwasher, people can compare products within categories. They can evaluate the pros and cons of the item they’re considering.
Side-by-side comparisons are rare in the world of pharmaceuticals. Drug companies rarely do studies that test how safe and effective their medicines are compared to the competition. Should you wish to know whether omeprazole (Prilosec) is better or safer than its chemical cousin esomeprazole (Nexium), you will have a hard time finding an answer.
You can compare a Toyota RAV4 to a Honda CR-V thanks to Consumer Reports. CR provides numbers for things like price, reliability, fuel economy, emissions, acceleration, safety, comfort and owner satisfaction. When it comes to medicine, however, there is no easy way to determine how safe and effective a drug will be for you. This reader asked what on the surface seems like a simple question.
What Does Safe and Effective Really Mean?
A reader asks us the most basic question about medications:
“Is there any place a consumer can go to find the effectiveness of a drug that has been prescribed? And along the same lines, how can he/she determine the frequency and severity of that drug’s side effects?”
This is the homework anyone would want to do before taking a new medicine. In fact, any physician prescribing drugs should be able to find such information easily and share it with every patient. In truth, these essential data are more difficult to locate than they should be.
If you perform an online search for prescription drugs you often find an ad from the drug company at the top of the page. They offer you a list of side effects, but rarely, if ever, tell you how common they may be. Drug databases like Drugs.com, WebMD.com or RxList.com may provide long lists of common side effects as well as less common adverse reactions. Most people probably zone out after the first few complications. It’s hard to make sense of these lists.
The FDA Has Unique Definitions for “Safe” and “Effective”
The FDA has two criteria for approving a new medicine. It has to be effective and it must be safe. Sadly, though, the definitions of effective and safe are hard to pin down.
How does the FDA determine that a drug works? It requires the manufacturer to demonstrate that the medication is better than an inactive placebo. It doesn’t have to be a lot better; it only has to demonstrate statistical significance. An antidepressant may be only 5 to 10% better than a sugar pill at relieving depression and the FDA is likely to give it a green light.
As for safety, all you have to do is turn on your television to realize that many FDA-approved drugs can cause serious or even life-threatening side effects. The FDA considers a drug “safe” even if it causes heart attacks, strokes, liver failure, kidney disease, cancer or death in some patients. We don’t know about you, but that doesn’t seem very safe to us.
Are You Sick of Rx Drug Commercials?
Prescription drug commercials on television are virtually worthless as a source of usable information. Almost every ad starts with a story about the wonders of the medicine. You are rarely told how often the drug actually works to resolve the health problem.
As an example, watch a commercial for the antidepressant Latuda (lurasidone). You are told that this drug is “proven effective for people with bipolar depression.” If you are not too distracted by a dog chasing a ball, you can read on the screen that “results may vary.”
How Safe and Effective Is Latuda?
What you aren’t told is what the success rate is. Even the official prescribing information is difficult to interpret. There is a rating scale from 0 (meaning no depression) to a maximum score of 60. When you subtract out the placebo effect, the drug reduced bipolar depression by 4.6 points. How that translates into something the average patient can understand is unclear.
The announcer warns viewers to:
“call your doctor about unusual mood changes, behaviors or suicidal thoughts…Elderly dementia patients on Latuda have an increased risk of death or stroke.”
Other side effects may include:
Fever, stiff muscles and confusion which could signal a life-threatening reaction. In addition, patients might experience uncontrolled muscle movements which could become permanent. High blood sugar, low white blood cell counts, dizziness on standing, seizures, increased cholesterol, weight or prolactin, trouble swallowing, and impaired judgement could all result from taking this medication.
You can’t tell how likely you are to experience the benefit or the adverse reactions. This leaves many people confused and frustrated.
We suspect that many viewers tune out the side effects because they have no way of judging if these problems are common or extremely rare. Their doctors may not know either. The data in the official prescribing information is not always accurate.
How Safe and Effective Is Prozac?
Take an older antidepressant called fluoxetine (Prozac). The official prescribing information tells doctors, nurse practitioners and pharmacists that the incidence of lowered sex drive with the drug is about 3%. They are also informed that erectile dysfunction only occurs in 2% of male patients.
A prescriber might not even bother to mention such adverse reactions since they seem so rare. And yet if you go to the medical literature you will discover that this class of SSRI antidepressants has quite a different track record.
One review observed that (Neuropsychiatric Disease and Treatment, April 20, 2020):
“Some studies reported up to 80 percent of SSRI-induced sexual side effects.”
What About Atorvastatin (Lipitor)?
Then there is atorvastatin (Lipitor), It is the most frequently prescribed cholesterol-lowering drug. Many doctors think of it as a life saver. And in fact, during a clinical trial fewer people taking the statin died of a heart attack (1.9 percent) than those taking placebo (3 percent).
This means that roughly one person out of 100 people taking Lipitor escaped a fatal heart attack. That is statistically significant, but it also means that 99 people taking the drug did not get that benefit.
Death, The Ultimate Statistic!
When measuring the effectiveness of any drug you have to ask a fundamental question. Effective for what? If you have a bad headache, you would determine the effectiveness of Advil, aspirin or Tylenol by how fast the headache completely goes away.
When it comes to statin-type cholesterol-lowering drugs, the most important metric is mortality. Did the drug prolong life? Yes, avoiding a heart attack is important. Ultimately, though, people want to know if their medicine will extend their lives.
It comes as a great shock to many physicians to learn that many randomized clinical trials of statins did not lead to a mortality benefit. Here are some examples:
In 2005 the TNT (Treating to New Targets) study was published in the New England Journal of Medicine (April 7, 2005). Over 10,000 patients with coronary heart disease were randomized to either 10 mg of atorvastatin or 80 mg of atorvastatin. There was a 2.2% reduction in major cardiovascular events in the intensive treatment group.
“There was no difference between the two treatment groups in overall mortality.”
In theory, the people getting 80 mg of atorvastatin should have done far better than those on 10 mg. Hmmm, what went wrong?
The IDEAL study involved 8,888 patients who had already had a heart attack (JAMA, Dec. 28, 2005). Half got 20 mg of simvastatin and the other half got 80 mg of atorvastatin. The expectation was that the intensive atorvastatin treatment would produce dramatic results.
“In this study of patients with previous MI [myocardial infarction or heart attack], intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events…There were no differences in cardiovascular or all-cause mortality.”
You might argue that the TNT and IDEAL study were not a comparison of statin to placebo. You would be right. They compared aggressive statin therapy that really lowered LDL cholesterol dramatically with much more modest treatment. One might suggest that any statin treatment (low or high dose) produces substantial benefit. That’s why the ASPEN trials is so important.
ASPEN stands for Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints (Diabetes Care, July, 2006). The investigators selected 2,410 subjects with type 2 diabetes. These people are like canaries in the coal mines. They are highly susceptible to heart attacks and early death from cardiovascular disease.
In this study, patients received either 10 mg of atorvastatin or placebo. LDL cholesterol was lowered 29% in the statin group. After four years, however, there was no statistical difference in outcomes between the patients on atorvastatin and placebo. In other words, there were no meaningful reductions in heart attacks, strokes, bypass surgery or heart symptoms in the group on statins. Most important, there was no mortality benefit.
Putting Effectiveness into Perspective:
It’s not that statins are ineffective. There are other clinical trials that show a reduction in heart attacks and strokes and a mortality benefit.
How much of a mortality benefit? One of the most famous statin studies was called 4S. After almost six years of simvastatin use, the survival gain was less than a month (27 days to be precise)(BMJ Open, Sept. 24, 2015). These were very high-risk patients. They had either experienced a heart attack or were having serious symptoms of heart disease.
The trouble is that randomized clinical trials have produced contradictory and confusing results. It becomes very hard to say how effective statins are in preventing any given individual from experiencing a heart attack, a stroke or extending life.
How to Discover How Safe and Effective Your Drug Is:
Where do you find this information? For many drugs, the best place is DailyMed. https://dailymed.nlm.nih.gov/ This online resource contains the information that FDA and the drug companies think is essential for doctors as well as patients. Section 14 on Clinical Studies describes the results from the trials presented to support the drug’s approval. Trying to make sense of the statistics can be challenging, but that is one of the few places to check actual effectiveness.
What About Safety?
Assessing safety can be even more daunting. DailyMed also has the official prescribing information in its adverse reactions section (Number 6 Adverse Reactions). Here too, the drug is compared to placebo.
If you look up the weight loss drug Contrave (naltrexone and bupropion), you will discover a black box warning. This is the closest thing the FDA has to waving a red flag to signal serious danger.
In the case of Contrave, the warning reads:
“In patients of all ages who are started on CONTRAVE, monitor closely for worsening, and for the emergence of suicidal thoughts and behaviors.”
In addition, Contrave causes nausea in about one third of patients. That compares to seven percent of those on placebo. Constipation, headache, vomiting and dizziness are also significant side effects along with insomnia, dry mouth and diarrhea.
The official prescribing information is a good first step but it does not always represent the final word on effectiveness or safety. Important adverse reactions are often discovered many years after the drug was approved.
One place to look for such information is PubMed.
This service of the US National Library of Medicine gives everyone access to brief summaries published in medical journals. Learning to use these resources is the first step to understanding how safe and effective your medicine may be.
You may also want to search for your medicine here at PeoplesPharmacy.com. We have a drug library and an herb library at this link. Of course you can always put any medication into the main search engine and you will discover lots of information side effects, interactions, generic drug problems and how to stop a medicine safely.
You may also find our book, Top Screwups of great value. It provides a drug safety questionnaire that you can photocopy and give to your physician and pharmacist. It also uncovers the most common mistakes doctors and pharmacists make when prescribing and dispensing medicine. Before taking any medicine, patients should request accurate, up-to-date, quantitative data about the benefits and risks of any prescription.
How do you know how safe and effective your medications are? We would love to know how much information your prescriber provides and how much you have to discover on your own. Please share your story in the comment section below. If you think this article is worthwhile, please share it with friends and family.