The double-blind, placebo-controlled trial is considered the “gold standard” for clinical trials, because it has the best chance of determining whether an active treatment is effective. This is true for several important reasons:
- Because no one knows if they are receiving active treatment, the chances are reduced that any benefit seen will be due to the placebo effect.
- People with ALS are a diverse group. One important way in which they differ is in the speed of progression of their illness: some people progress slowly, while others, unfortunately, progress more quickly. By randomly assigning subjects to active treatment and placebo groups, that diversity is spread equally between the groups. This increases the chances that any benefit seen will be due to differences in treatment, rather than differences in the patients in each group.
The fastest way to develop new treatments for all people with ALS is to test new drugs in studies designed to give the answer quickly and without doubt. Currently, this is only possible by comparing the active treatment (new therapy) with a placebo.
Two recent ALS clinical trials show how important double-blind, placebo-controlled trials are in weeding out ineffective treatments:
- An open-label trial of lithium in a small number of patients suggested this drug helped slow the disease. But a larger, placebo-controlled, double-blind trial found no effect. Without that trial, many ALS patients may have gone on to take a useless medication.
- Animal studies and open-label human trials suggested the antibiotic minocycline was beneficial. But a larger, placebo-controlled trial showed it was not, and may even have been harmful. Without that larger trial, patients may have continued taking minocycline, causing harmful effects without helping their disease.
Only with placebo-controlled trials could these two treatments be ruled out as ineffective in ALS, saving patients from taking medicines that offer no benefit and that could even be dangerous. An important point to remember is that experimental drugs are indeed experimental. That means that the drug can have a positive effect, no effect at all, or be detrimental. It is sometimes difficult to keep in mind that a patient on a placebo may actually be getting better treatment than someone on the active medication. A trial with a negative result is very disappointing to both participants and study organizers. But every trial teaches us something valuable and makes subsequent trials more likely to succeed. The disappointment of negative trial results such as these only strengthens our commitment to finding truly beneficial treatments for ALS. That work can only succeed if patients enroll in clinical trials.