This book delineates the fundamental transformations that, according to its precepts, are now needed in the objects and methods of 'patient-oriented' clinical research, in order to make it genuinely patient-relevant. These transformations are presented as providing for transition from today's 'evidence-based' practices (advocated by 'clinical epidemiologists') to knowledge-based succedanea of these. While those existing practices vary according to doctors' personal opinions about the burden of the available evidence, their knowledge-based succedanea will be essentially invariant across individual doctors, as they'll be guided by 'expert systems' (imbedded in cyberspace). At issue in this is transformation in what the authors present as the very essence of clinical medicine, namely clinical doctors' esoteric ad-hoc knowing: "gnosis." This is clinical doctors' knowing - probabilistic - about relevant-but-hidden truths about their patients' health, and constitutes the basis for their teaching ("doctoring") the patients about these esoteric insights. The probabilities are 'personalized' in the meaning of their specificity to the cases' gnostic profiles. Genuinely patient-relevant clinical knowledge this book presents as the requisite basis for three species of clinical doctors' gnosis: diagnosis - knowing about whether a particular type of illness is present (though hidden) in the patient; etiognosis - knowing about whether the patient's illness was caused by a particular antecedent of it; and prognosis - knowing about the patient's future health, including as to its dependence on the choice of treatment. Pivotal in gnostic clinical research this book presents to be the studies' objects design in terms of a statistical model for the rate of occurrence of the entity of health in question, in a defined domain of case presentations. The essentials of the studies' methods designs are deduced from their objects designs. Study of this book - on the theory of "meta-epidemiological clinical research" - is essential preparation for teaching 'patient-oriented' clinical research and for actual design & conduct of the studies and of their critical reviews. And by the same token, study of this book is essential preparation for the needed replacement of 'case-based learning' of clinical medicine, for suitably-learned teaching of the practice of clinical medicine - focused on the status quo of the scientific knowledge-base for (gnoses in) the discipline ('specialty') at issue.