Porzsolt and Jauch highlight so-called „ideal conditions“. It may be that narrowly defined conditions are necessary for certain issues. However, equating randomization and „ideal conditions“ is fundamentally wrong. If one is even interested in the „real-world benefit“—and this idea is little more than a buzzword, then of course you can and should study this in an RCT. Nothing rules out using so-called pragmatic RCTs, as addressed in our publication (1). Tools other than RCTs are usually unnecessary, more elaborate, and (as everyone knows) provide less reliable results. In fact, only recently, authors of a study with so-called real-world data almost distanced themselves from their own results: despite a significant difference observed in favor of therapy escalation, they still were unwilling to base a recommendation on it („real-life data are exposed to important potential biases“). (2). Nobody needs this (3).
Indeed, the main question is whether effects under the conditions described as „ideal“ are different from others (effect modification). If one is interested in effect modification, then it would be highly unwise, for clarification in the context of another study, to change not only one factor for all study participants („real-world“ instead of „ideal“) but at the same time also a second one (non-RCT instead of RCT). In this case, differences in outcome in the two studies could not be attributed to any specific factor. Incidentally, evidence for obtaining significantly distinct effects in this way is surprisingly sparse.
Torremante rightly states that randomized trials should not replace medical observation and intuition. We would also like to emphasize his statement that one‘s “own judgment” is required. However, the statement that RCTs play no role for antibiotics and vaccinations is not correct. Especially for vaccinations, drawing a conclusion about positive or negative effects due to „clinical assessment“ is simply impossible. No one will be able to determine whether the fact that someone did not get the flu was due to being vaccinated or simply to not getting infected. The importance of using RCTs for vaccinations (for example, the HPV vaccine) as well as for antibiotics is self-evident, and it is equally evident that RCTs should be the basis of their assessment.
Tsamaloukas identifies equipoise as „a central problem in the ethics of clinical research“. A call for equipoise as the most important ethical prerequisite is probably not helpful for the feasibility of RCTs, and if at all, then it should apply also to all other study types; we have addressed this in a further article that shall appear shortly in this journal.
On behalf of the authors:
Dr. med. Dipl.-Psych. Jörg Lauterberg
IQWiG – Institute for Quality and Efficiency
in Health Care
Conflict of interest statement
The author declares that no conflict of interest exists.
|1.||Lange S, Sauerland S, Lauterberg J, Windeler J: The range and scientific value of randomized trials—part 24 of a series on evaluation of scientific publications. Dtsch Arztebl Int 2017; 114: 635–40 VOLLTEXT|
|2.||Delaloge S, Pérol D, Courtinard C, et al.: Paclitaxel plus bevacizumab or paclitaxel as first-line treatment for HER2-negative metastatic breast cancer in a multicenter national observational study. Ann Oncol 2016; 27: 1725–32 CrossRef MEDLINE|
|3.||Macleod MR, Michie S, Roberts I, et al.: Biomedical research: increasing value, reducing waste. Lancet 2014; 383: 101–4 CrossRef|