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The thesis consists of an introduction and two papers. In the introduction a brief historical survey of empirical investigations into the effectiveness of medicinal interventions is given. Also, the main ideas of the EBM (evidence-based medicine) movement are presented. Both included papers can be viewed as investigations into the reasonableness of EBM and its hierarchies of evidence. Paper I: Typically, in a clinical trial patients with specified symptoms are given either of two or more predetermined treatments. Health endpoints in these groups are then compared using statistical methods. Concerns have been raised, not least from adherents of so-called alternative medicine, that clinical trials do not offer reliable evidence for some types of treatment, in particular for highly individualized treatments, for example traditional homeopathy. It is argued that such concerns are unfounded. There are two minimal conditions related to the nature of the treatments that must be fulfilled for evaluability in a clinical trial, namely (1) the proper distinction of the two treatment groups and (2) the elimination of confounding variables or variations. These are delineated, and a few misunderstandings are corrected. It is concluded that the conditions do not preclude the testing of alternative medicine, whether individualized or not. Paper II: Traditionally, mechanistic reasoning has been assigned a negligible role in standard EBM literature, although some recent authors have argued for an upgrading. Even so, mechanistic reasoning that has received attention has almost exclusively been positive -- both in an epistemic sense of claiming that there is a mechanistic chain and in a health-related sense of there being claimed benefits for the patient. Negative mechanistic reasoning has been neglected, both in the epistemic and in the health-related sense. I distinguish three main types of negative mechanistic reasoning and subsume them under a new definition of mechanistic reasoning in the context of assessing medical interventions. Although this definition is wider than a previous suggestion in the literature, there are still other instances of reasoning that concern mechanisms but do not (and should not) count as mechanistic reasoning. One of the three distinguished types, which is negative only in the health-related sense, has a corresponding positive counterpart, whereas the other two, which are epistemically negative, do not have such counterparts, at least not that are particularly interesting as evidence. Accounting for negative mechanistic reasoning in EBM is therefore partly different from accounting for positive mechanistic reasoning. Each negative type corresponds to a range of evidential strengths, and it is argued that there are differences with respect to the typical strengths. The variety of negative mechanistic reasoning should be acknowledged in EBM, and presents a serious challenge to proponents of so-called medical hierarchies of evidence. QC 20150413