10. 9. 2011
Prague Psychiatric Centre & Charles University, 3rd Medical Faculty, Prague Czech Republic
Placebo is a "sham" or simulated medical intervention, usually a medicament containing no pharmacologically effective substance. The name comes from a part of Psalm in Latin, placebo Domino in regione vivorum. Originally in France this was a label for „simulants“ pretending a grief at funerals and singing „placebo Domino…“ to get some food and drink. Arguments pro and con use of placebo in clinical research are coming from three domains: methodological, ethical and technical.
From the methodological point of view the notion prevails that without placebo-controlled double blind studies the proof of efficacy of a new drug is almost impossible. The active comparator may not have had a stable and reliable efficiency, which reduces the value of individual studies. On the other hand the fact that substance B is not superior to substance A and substance A is not superior to placebo does not inevitably mean that substance B is not superior to placebo. Therefore a direct comparison with placebo is often necessary.
From the ethical perspective the Helsinki declaration is often quoted. Article II.3 says that the benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention. This condition would not be met with placebo. Moreover, even a new tested drug may not be finally proven „the best current intervention” (this is only going to be proven). This condition of the Helsinki declaration therefore cannot be met unless the whole research of new therapeutics is completely stopped and even the prescription of some old experienced medicaments, the efficiency of which is not in certain indications based on enough evidence, is banned, e.g. Vitamin C in flu or acetylsalicylate in cardiovascular attacks prevention. Here the public (to bring new treatments) and the individual (to be treated lege artis) interests clash. This paradox is now solved by diminution of the respective wording: The use of placebo, or no treatment, is acceptable in studies where no proven intervention exists or where for methodological reasons it’s use is necessary.
In technical terms it is sometimes difficult to ensure blinding of the placebo, especially where the tested drug belongs to a group of substances with known side effects such as parkinsonism in antipsychotics, absence of which indicates that the patient was randomized to the placebo arm.
In general, the major problem of clinical pharmacology is a significant increase of the effect of placebo in recent years accompanied by considerable fading of a signal between active drug (verum) and placebo. Design of a study, type of institution, patients characteristics, rating factors, type of a rating scale, outcome measure, type of a symptom or a disease (pain vs diabetes), type of medication and dosing schedule (frequency of contact with a carer), sample size, randomization (regression toward average), sensitivity to placebo (cultural context), and qualification of raters may contribute to the observed decrease of the verum-placebo signal.
In addition, the use of placebo in combination with ethical concerns moves clinical studies far away from the real environment, particularly because of the exclusion of suicidal, severe, aggressive, alcohol and drug dependent or comorbid patients, what is however often a clientele in everyday practice. The results of such academic research thus become hardly applicable in routine clinical practice.