What is new? The current research/care demarcation should be revised. Optimal medical care continuously needs evaluation and revision. Some trials can be designed to (1) regulate unvalidated actions within medical care and (2) demarcate validated from unvalidated care Verifiable medicine can be practiced when care and care research are conjugated.
The most urgent problem of modern medicine is how can patients be treated in a transparent, prudent, and verifiable manner? This question applies to any intervention, whether it is a screening test [1], a change in diagnostic criteria [2], an imaging study [3], preventive care [4], the use of new devices [5], surgical innovations [6], or even prognostic studies if they impact on decision making [7]. What these interventions have in common is an action, an intrusion into the lives of vulnerable individuals. Such intrusions must be justified if they are to be prescribed with authority by trustworthy physicians. The justification for an action carried out on a patient must be the reliable demonstration that, in general, it leads to better outcomes. But how can a medical action be justified before it has been shown to be beneficial? This article proposes care trials, pragmatic trials used as patient care, as the best possible solution to this problem.
Three great barriers must be addressed. First, the current research care dichotomy must be revised. A prevailing view conceives clinical research as an enterprise dedicated to gain knowledge for the benefit of future patients. This view misses the normative role research methods can play immediately, in guiding medical actions and simultaneously providing the best possible care to patients given the uncertainty. When current care includes interventions that have yet to be proven beneficial, proper research methods must be brought into the sphere of care. Patients need a distinction between validated care (care confirmed to be beneficial by rigorous research) and clinical care research (care in the process of being evaluated). The fundamental ethical principle underlying the practice we propose is that physicians should either (1) provide validated care and refrain from using tests or treatments that have never been validated because they may be harmful or (2) offer promising interventions only within declared research, designed in the interests of those same patients needing care.
Care trials may play a dual role in this program: they are the test that an intervention must pass to qualify as validated care; in the meantime, care trials are the rational and ethical means to care for patients despite the shortcomings of our knowledge regarding what to do. In this context, the trial must be designed for the interests of the present patient in such a fashion as to address a number of ethical concerns, such as the notion that the patient is being used for the benefit of science [8], the therapeutic obligation (the notion that clinicians should offer the treatment they prefer) [9], and the therapeutic misconception (the notion that patients falsely believe they are being cared for when they are research subjects) [10]. With a proper trial design, these concerns can be addressed.
A second great barrier is practical: the financial, bureaucratic, and organizational obstacles to trials which view care, no matter how poorly justified, as a necessity, whereas research is a luxury [4]. It may be unrealistic to expect that all currently practiced unvalidated interventions will be trialed. However, if proper trials can be conducted to evaluate and limit unverified care, these obstacles should be removed.
The third and perhaps greatest barrier is cultural. Outside research, physicians and patients are led to believe that a single best treatment can be found in each particular case, even in the absence of evidence [4]. Uncontrolled interventions are used on a large scale, perpetuating a practice based on dogma, belief, custom, or fashion. This barrier can perhaps be addressed by reconstructing the ethical role that trial methods play in guiding conduct, by exposing how the design makes the trial optimal care. This cultural obstacle may slowly abate as care trials become customary. To make them realistic and accessible, their review and implementation must be simple and timely. If they are to be prioritized by patients, physicians, and institutions as optimal care, they must satisfy some criteria. To help research ethics committees identify the protocols that qualify as care trials, a checklist is provided along the CONSORT guidelines (Table 1) [11], [12]. Trial characteristics can also be displayed in a graphic form inspired from the pragmatic-explanatory continuum indicator summary [13], to readily identify trials that entail extra tests, risks, or costs (Fig. 1). Perhaps unsurprisingly, the end result resembles a pragmatic trial [13], [14], [15], [16]. This means there is no conflict between what is best for the patient and what will be the best way to judge the value of medical interventions. All pragmatic trials are not care trials, however. While pragmatic trials are designed to gain knowledge to inform decisions, care trials primarily guide clinical actions although knowledge remains lacking. The label remains important to emphasize the protection of present patients in need of care, which necessitates (1) methods that may affect usual care and (2) rules that ensure that the trial will not be devalued in favor of other interests (such as collecting interesting scientific observations). If the trial meets these criteria, competition for research funding, waiting for extra personnel or for contracts between institutions can only harm patients. The ultimate goal is to practice a verifiable medicine that patients can trust.
Care trials have a dual role. First, they offer optimal care in the presence of uncertainty (to protect each present patient). Patients and physicians are frequently confronted with an unresolved clinical dilemma. Clinical judgment may suggest that a test or treatment, standard or new, is preferred, but the belief that the intervention is beneficial remains an untested hypothesis; there is nearly always an alternative that has previously been validated. If not, doing nothing may be a prudent
The care trial concept has yet to be developed, adapted, and thoroughly tested in real medical practice. Care trials could, for one thing, be the optimal way to introduce new tests or interventions. The first real-life application of this concept, in our relatively small field, is the FIAT trial, which was designed to “provide a prudent, controlled clinical context for the use of flow diversion (FD), a promising but as-yet unproven treatment option for patients with difficult intracranial
Conventional trials are conceived to gain knowledge of causal mechanisms (explanatory trials) or of efficiency of treatment options (pragmatic trials). The knowledge that is gained is intended to help decision making regarding future patients. This emphasis on knowledge leaves many current patients subject to either unvalidated case-by-case care or research designed for the benefit of future patients. Care trials resemble pragmatic trials [13], [14], [15], [16], but it is the immediate
Care trials can help to identify which medical alternative should be the standard therapy. In the meantime, they provide optimal care in the presence of uncertainty.
Conflict of interest: J.R. was influenced by the premature interruption and failure of the TEAM trial, for which he was the principal investigator. J.R. and T.E.D. are investigators on a number of trials dealing with the treatment of intracranial aneurysms.
Funding: The study benefited from no financial support.
