Two new series are being launched in Intensive Care Medicine. The first one starts in this issue and concerns the process of clinical research, with a special focus on legal and ethical aspects in intensive care medicine. The series is directed by François Lemaire, who also authors the first paper, dealing with the doctors' trial in Nuremberg [1]. Why such a terrible story to open the discussion of innovations applied to patients today? First, simply because all modern rules about ethics applied to medical research, such as patient's information and consent to research, come from there. Second, and unfortunately, because it illustrates in a very sad and extreme manner the ambiguity underlying clinical research, which is conducted to improve our knowledge for the good of future patients but not specifically for the benefit of the particular patient under scrutiny in a given research protocol. Undoubtedly, the functional evaluation performed during a clinical research trial or the application of a strict management procedure can benefit individual patients enrolled in such trials. This is not, however, the main objective of a clinical research protocol. In addition, it is often claimed that patients enrolled in research protocols tend to do better than patients outside a protocol. There is, however, very little evidence that this is true, or even that it is usually true. In a study by Vitacca and coworkers comparing two modalities of weaning from mechanical ventilation in ventilator-dependent patients, the authors reported that entering either of two research arms seemed to benefit patients compared with an historical group [2]. The benefit seemed to be explained entirely by the systematic assessment performed at study entry and not specifically by the rest of the protocol. By contrast, it was shown that patients not entering the ARDS-Net low tidal volume study had a mortality similar to patients randomized to the low tidal volume arm [3], which may indirectly suggest that enrolled patients randomized to the high tidal volume arm could have been harmed by the protocol. Such comparisons, should be interpreted cautiously, for obvious reasons, but illustrate the lack of strong data saying that being enrolled in a research protocol is always good. The physicians judged during the Nuremberg trial, motivated by their desire to increase their knowledge, adopted an extreme attitude in which the individual patient's life was of no value and only the – highly debatable – “benefit” for science of the “research” counted. The intense debate generated by this behavior helped to build strong foundations for ethics in clinical research. This story is thus an apt initiation of this series on the ethical and regulatory aspects of clinical research.
The second series, entitled “Mini-series: Basic Research-related Reviews in Intensive Care Medicine”, begins in a forthcoming issue and will be under the responsibility of Herwig Gerlach as Associate Editor. As Herwig will describe in an editorial, with these series we are striving to minimize the distance between basic research and clinical practice. One fundamental aspect of our discipline is that we are facing highly complex situations and patients. Therefore, in any individual case we need to understand the mechanism underlying the severe physiological derangements often referred to as organ dysfunctions or failures. Incorporating physiology and pathophysiology into our everyday reasoning at the bedside is necessary to apply urgent and potentially harmful treatments in the best possible way. Cookbook recipes are often of limited value in such situations. In the journal we have repeatedly tried to offer the readers some clues regarding the history of concepts (Seminal Studies in Intensive Care [4, 5, 6]), or about major physiological trails (Physiological Notes [7, 8]), thus providing information useful at the bedside for setting the ventilator, understanding hemodynamic disturbances, monitoring intracranial pressure or optimizing renal replacement therapy, for instance. For a number of modern therapies or strategies, we also need to understand the cellular or molecular mechanisms behind the physiological abnormalities or justifying the new treatments. This will be announced with more details soon.
Research is like a continuous, never-ending jigsaw puzzle. There are so many pieces to add before we can see the whole picture. Every piece of research is like looking at the details of a painting by Cezanne. Often, with surprise, one can observe (and recognize from painting to painting) all those little colored rectangles; one can then easily imagine the motion of the brush that made these rectangles and the hand holding the brush. Because a rectangle is green or brown you understand that it represents nature. However, you need to walk several steps backward to make the rectangles vanish and a beautiful landscape of the French Provence appear. You then understand that these numerous little brush strokes were what made it happen. For research, we try to publish as many little colored rectangles as we can, hoping it will help to give a broader view of medicine.