Bioequivalence and Bioavailability Forum

Hi Dennis,

❝ ❝ Essentially you are trying to show that the medicine doesn’t perform better than placebo (assuming the study is double-blind). 

❝

❝ But I have to confess that I'm a little bit confused.

❝ Dose the effect of placebo could be consided as the effect of patinets without medicine in the situation of our study?

❝ that is, the effect of patinets with placebo equal to the effect of patinets without medicine in our study?

Oh dear! Depending on the drug, the disease, and the setting (administration at home or by an affectionate and trustworthy ‘God’ with horn-rimmed glasses wearing a white coat with a stethoscope around the neck), the placebo effect amounts up to 30%.^1,2 Studies to assess the placebo effect are difficult.³

When we assess the effect of a drug, it’s always against the placebo effect and not against ‘nothing’.

❝ ❝ Can you elaborate a bit – without naming the good stuff – what ‘traditional’ means in this context? Any studies demonstrating its efficacy & safety? Or ‘traditional’ like ‘It’s used for ages and obviously [sic] it works’.

❝

❝ The medicine is a common prescription medications.

OK, that helps.

---

1. Seemingly there is an ‘optimal’ size of a placebo in adults. If the pill is relatively small → little ‘content’, low effect. If it is larger → difficult to swallow, must be great stuff, higher effect. If is really large → distrust, low effect.
   
   
2. Once researchers were interested whether the color (‼) of a sham ‘sleeping pill’ influenced the placebo effect in European patients. It turned out the blue one ‘worked’ best in almost all countries (blue associated with calmness, dusk, …).
   There was one exception – Italy. ⚽ Football/soccer is a kind of religion in Italy. The national team is called the Squadra Azzurra (the azure team). Hence the associations were awareness, speed, sta­mina, you name it. No way to fall asleep.
   
   Obviously Pfizer didn’t know this study. Why is ➡️ this goody blue in all countries? Cause it was originally approved for males (boys = blue, girls = pink)? Should consider a modification.
   
   
3. One option is to compare a treatment vs placebo in two studies. One is double-blind and the other open-label. There are even ones where the sub­jects are told:
   • This is a placebo. It’s just a pill made from starch and sugar. It does not contain any active ingredient at all. You shouldn’t expect to experience an effect.
   Then compare the placebo-arms of both studies. Power of such a comparison is poor. Com­monly a meta-analysis of many studies is performed.

Images from Wikimedia Commons. First © 2013 Michael J. Ermarth @FDA, second © 2006 user SElefant.