Some medications are life saving. I am so thankful for the trusty med that tames my atrial fibrillation.
Many meds are helpful -- demonstrating superiority to placebo in ways that are clearly clinically significant and life enhancing.
But many (perhaps most) drugs are probably no more than very expensive placebos. Patients get prescriptions from doctors when their symptoms are most severe and improve with time and positive expectation, not because the med is really effective.
Doctors and patients need independent, objective information on drug efficacy and risks.
The multibillion dollar pharma marketing machine can turn even the most useless and harmful drugs into financial blockbusters. Doctors and patients need independent, objective information on drug efficacy and risks.
This is the first of a series of blogs aimed at setting the record straight. Dick Bijl is President of the International Society Of Drug Bulletins (ISDB), a wonderful organization representing 53 national drug bulletins, each charged with presenting the best available data on the pluses and minuses of different medications. Drug bulletins are a source of truth to help patients and doctors see through the fudged misinformation generated by ubiquitous Pharma propaganda.
Dick writes: "Let's use the treatment of lower urinary tract symptoms (LUTS) as a typical example of why and how medication use has become so excessive."
Elderly men often experience problems urinating -- weak or intermittent urinary stream, straining, hesitancy, terminal dribbling, incomplete emptying, urgency, frequency, incontinence, nocturia and/or post-micturition dribbling. These symptoms, so common in aging, provide a lucrative target market for pharma.
In the past, benign prostatic hyperplasia (BPH) was regarded as the most important cause of urinary symptoms. Nowadays, evidence confirming a link between LUTS and prostatic enlargement is regarded as weak. This hasn't prevented approval of many drugs for the treatment of BPH by the Food and Drugs Administration (FDA) and the European Medicines Agency (EMA).
The bar for approval is set very low. Drug companies have only to show that their medication has a statistically significant advantage when compared to placebo. The FDA and EMA don't require that the med achieve what is ever so much more important- clinically relevant improvement as evidenced by patients actually also feeling and doing better when taking the drug. Small statistical blips are all it takes to get a drug approved.
There is a huge difference between statistical significance and clinical relevance. For example, the International Prostatic Symptoms Score is often used to quantify the treatment effects of urinary drugs. The IPSS scale goes from 0-35 with higher scores indicating more severe symptoms. A difference of ≥3 points = some effect; ≥5 points = moderate effect; ≥8 pt. = clear effect). In practice, it turns out that patients can't detect improvements if they are less than three points.
The results of clinical trials have shown that most drugs used to treat BPH are statistically more efficacious than placebo, but have no real clinical relevance. Because their improvement was less than three points, patients will not detect any difference between these drugs and placebo.
The same lack of clinical relevance holds for drug combinations. A combination of an alpha blocker and a 5-alpha reductase inhibitor or an alpha blocker and an antimuscarinic drug often results in statistically significant decreases in symptoms compared to placebo or to the individual drugs given alone. But here also, the differences were of such small magnitude that patients will not detect them.
Only in a small minority of clinical trials was the decrease in symptom score more than 3 points.
The lack of efficacy of BPS meds supports a policy of watchful waiting instead of starting drug therapy. The natural course of LUTS is quite favorable and in the majority of patients the severity of the symptoms will not increase.
Most (or all) of the relief patients feel taking the med is probably due to natural improvement or placebo effect, not to the med itself -- but they don't know this and will often misattribute benefit to the drug.
And almost all the drug studies have been performed in secondary and tertiary care. The results of these studies can't simply be generalized to primary care because it is not plausible that these patients have the same characteristics and therefore the same prognosis.
It's not rational to prescribe drugs that do not improve functioning more than placebo. Use of medication for LUTS should be discouraged since it is no better than placebo, but adds the risk of side effects. Counseling and re-assurance should be considered first.
Informed patients will be much less willing to take a drug that carries the risk of side effects, while offering at best only a very slight improvement in symptoms.
Whenever it is decided to start drug therapy, the best choice are alpha blockers. Side effects should be taken into account: fatigue, decreased vision, severe postoperative ophthalmological side effects or complications, orthostatic hypotension leading to headache and dizziness.
5-alpha reductase inhibitors should not be regarded as an alternative because of their small efficacy and side effects like gynecomastia, erection and ejaculation disorders, decreased libido, impotence, and breast cancer.
The antimuscarinics do not have a positive balance of efficacy and they have anticholinergic side effects (e.g., dry mouth, abdominal pain and constipation). Phosphodiesterase inhibitors have been introduced in recent years but studied insufficiently in comparative studied to give them a place. Combination-therapy should not be given because it does not have an added value related to clinical relevance but does add side effects.
We conclude that the natural course of LUTS in men is generally favorable; the pathophysiology of LUTS is not clear; the relation between prostatic volume and urinary complaints is weak; the mechanisms of action of meds is uncertain; and positive effects are small in placebo-controlled studies.
Therefore, primarily counseling and non-drug treatment are indicated and drug-treatment should be discouraged. In case a drug is needed only an alpha blocker is indicated, but this often just a very expensive placebo-therapy."
Thanks Dick for this illuminating analysis. Before considering any med useful, we should subtract placebo effect from reported efficacy- and also consider the considerable risk of med side effects and Pharma's ridiculously high prices.
In a rational world, people would be taking many fewer drugs, for much clearer indications, with benefits always balanced by consideration of risks, and with prices reflecting real value.
Medication use is now much more governed by pharma's commercial interest than by what is best for the patient.