Are prescription drugs truly safe?
Depends on how well and how long you look.
When I was discovered on endoscopy to have gastroesophageal reflux disease (GERD,) my gastroenterologist told me I should immediately go on proton pump inhibitors, known as PPIs. They were extremely efficacious. “And they’re safe. I’ve been on one for 16 years. You can take them for a lifetime without trouble.”
PPIs were breakthrough drugs. By preventing the production of stomach acid, they worked more effectively at suppressing Barrett’s esophagus, peptic ulcer disease and other common GI ailments than the H2 blockers they replaced. They become so commonly used that patients forget to mention them on drug lists. Patients would tardily remember they were taking a “purple pill” that “did something to my stomach.” Eventually some PPIs went over-the-counter.
Yet recently a Hong Kong Study in the British Medical Journal demonstrated something different. In patients who had helicobacter pylori, the bacterial infection that causes peptic ulcers, and then had that infection treated, the rate of stomach cancer was twice as high as among those taking PPIs than the older, cheaper, older H2 blockers. Other studies have identified PPIs as increasing the risk of Alzheimer’s, particularly important, as many of those on the drugs use them a long time, with many at the advanced age where Alzheimer’s strikes. Other recent studies implicate PPIs in chronic kidney disease and heart attacks. They have for some time carried FDA and other warnings regarding clostridium difficile infections, which kill tens of thousands; hip and spine fractures; pneumonia. Yet they are considered “safe.”
To understand our perception of safety, it’s important to know the natural history of drugs.
Drugs in Evolution
Pretty much everybody wants more effective agents for the common and uncommon ills of humanity. Drug companies are near the top of that list. Come up with a “blockbuster” and they make billions in profit, often tens of billions, and leave their chief executives very rich. One example: viagra is so profitable billions of dollars of fake viagra is sold every year.
The problem is finding stuff that works and is “safe.”
The human information system is remarkably complicated. So is manipulating it.
Drug companies do a fair bit of basic research. They troll through data bases and use AI to find promising compounds. Yet about 90% of drugs that go to clinical drug trials fail. Sometimes the issue is effectiveness. A very high portion of the time the problem is safety.
What happens in preliminary laboratory and animal testing does not tell you a whole lot about how humans use and metabolize drugs.
These common failures affect the drug approval process. Most of the time drugs get tracked in clinical trials for weeks to months. However, the drugs that really make money for drug companies are used for extended periods, years to decades. That is one of the reasons why antibiotics are greatly underresearched. Once the patient is “cured,” they may never need the antibiotic again. One or two weeks’ use is “not enough” for drug companies to overcome their high cost of drug development.
That’s why drug companies are now being paid directly by governments to research new antibiotics. Public health departments throughout the world recognize that new epidemics of antibiotic resistant infections may kill and tens of millions. Some could represent an existential threat to much of humanity.
But the present drug development model “doesn’t make enough profits” for new antibiotics to get fully researched.
Time also matters. What happens when people are placed on new drugs and followed up? You start to find “side effects” no one imagined. Like kidney disease and gastric cancer and Alzheimer’s with PPIs. Stuff you will never notice given present reporting of medications in the U.S.
For more of the most frightening side effects of drugs take decades to become noticed. Not incidentally, that generally occurs after drug companies have lost their patent protections and peak drug profitability. The “redress” for these often expectable long term side effects often occurs through personal injury court cases. That is not a great place to set public health policy.
Why are PPIs causing so many troubles? It may be that their ability to cut off acid is “too” effective. They appear to markedly diminish acid production is lysosomes, cell organelles necessary to survival through destroying denatured proteins. Not enough acid, ineffective lysosomes.
So finding increases in stomach cancer, heart disease, kidney disease and Alzheimer’s with PPIs may not be so strange after all. The body’s information system is very complicated. Results may slowly ripple out.
What To Do
It’s obvious that drug effects occur over much longer ranges of time than the drugs themselves are taken. So it would make sense to have long term registries of drugs and their results that could be scrutinized decades into the future.
These registries exist, but are not welly funded. Drug companies are not particularly fond of them. More importantly, such registries should be international, paid for by government public health departments. Users of PPIs in Germany and Britain are not so different from those in the US. Pooling data across countries should identify problems more quickly, so preventive action can be taken.
But there is a stranger dimension to drug surveillance in the US. We are the only large country that allows drug company advertising.
It’s a very big business. And all media, including social media, don’t like losing business.
So when drugs are found to have “unwanted” long term side effects, the results may not be showcased in the media quite as brightly as would occur for other products. Combine multibillion dollar drug advertising with rules that prevent Medicare from negotiating drug prices and it is no surprise drug companies make the lion’s share of their profits in the U.S.