Mechanistic understanding in clinical practice: complementing evidence‐based medicine with personalized medicine

In the last century, medicine has undergone an unprecedented wave of radical changes. From the implementation of surgery up to the development of single gene‐targeted therapies, clinical decision making has become increasingly complex to handle. Today, this complexity needs to be rethought in the light of two emerging paradigms: evidence‐based medicine (EBM) and personalized medicine (P‐Med). The new availability of diverse sources of scientific evidence raises significant issues concerning how clinicians will compare, evaluate and orient their decisions in front of a rapidly growing plethora of therapies, procedures, medical technologies and drugs. In this paper, we compare the background visions behind these two paradigms, evaluating their respective relevance for present and future clinical decision making. In particular, we argue that EBM and P‐Med are driven by two diverse modes of reasoning about ‘evidence making’ in medicine. EBM is grounded on statistical notions and epidemiological data, generally gathered through systematic meta‐reviews of randomized controlled trials; P‐Med, instead, is grounded on mechanistic explanations of molecular interactions, metabolic pathways and biomarkers. While both paradigms are epistemically sound, we argue that they cannot, and should not, be hybridized into a unique model. Rather, they ought to represent two compatible, but alternative ways of informing the clinical practice. Hence, we conclude that clinicians may expect to see their responsibility increasing as they will deal with diverse, but equally compelling, ways of reasoning and deciding about which intervention will qualify as the ‘best one’ in each individual case.     

An epistemological shift: from evidence‐based medicine to epistemological responsibility

In decision making concerning the diagnosis and treatment of patients, doctors have a responsibility to do this to the best of their abilities. Yet we argue that the current paradigm for best medical practice – evidence‐based medicine (EBM) – does not always support this responsibility. EBM was developed to promote a more scientific approach to the practice of medicine. This includes the use of randomized controlled trials in the testing of new treatments and prophylactics and rule‐based reasoning in clinical decision making. But critics of EBM claim that such a scientific approach does not always work in the clinic. In this article, we build on this critique and argue that rule‐based reasoning and the use of general guidelines as promoted by EBM does not accommodate the complex reasoning of doctors in clinical decision making. Instead, we propose that a new medical epistemology is needed that accounts for complex reasoning styles in medical practice and at the same time maintains the quality usually associated with ‘scientific’. The medical epistemology we propose conforms to the epistemological responsibility of doctors, which involves a specific professional attitude and epistemological skills. Instead of deferring part of the professional responsibility to strict clinical guidelines, as EBM allows for, our alternative epistemology holds doctors accountable for epistemic considerations in clinical decision making towards the diagnosis and treatment plan of individual patients. One of the key intellectual challenges of doctors is the ability to bring together heterogeneous pieces of information to construct a coherent ‘picture’ of a specific patient. In the proposed epistemology, we consider this ‘picture’ as an epistemological tool that may then be employed in the diagnosis and treatment of a specific patient.     

Evidence‐based medicine: A cornerstone for clinical care but not for quality improvement

Quality improvement (QI) as a clinical improvement science has been criticized for failing to deliver broad patient outcome improvement and for being a top‐down regulatory and compliance construct. These critics have argued that the focus of QI should be on increasing adherence to clinical practice guidelines (CPGs) and, as a result, should be consolidated into research structures with the science of evidence‐based medicine (EBM) at the helm. We argue that EBM often overestimates the role of knowledge as the root cause of quality problems and focuses almost exclusively on the effectiveness of care while often neglecting the domains of safety, efficiency, patient‐centredness, and equity. Successfully addressing quality problems requires a much broader, systems‐based view of health‐care delivery. Although essential to clinical decision‐making and practice, EBM cannot act as the cornerstone of health system improvement.     

How evidence‐based medicine is failing due to biased trials and selective publication

Evidence‐based medicine (EBM) was announced in the early 1990s as a ‘new paradigm’ for improving patient care. Yet there is currently little evidence that EBM has achieved its aim. Since its introduction, health care costs have increased while there remains a lack of high‐quality evidence suggesting EBM has resulted in substantial population‐level health gains. In this paper we suggest that EBM's potential for improving patients' health care has been thwarted by bias in the choice of hypotheses tested, manipulation of study design and selective publication. Evidence for these flaws is clearest in industry‐funded studies. We argue EBM's indiscriminate acceptance of industry‐generated ‘evidence’ is akin to letting politicians count their own votes. Given that most intervention studies are industry funded, this is a serious problem for the overall evidence base. Clinical decisions based on such evidence are likely to be misinformed, with patients given less effective, harmful or more expensive treatments. More investment in independent research is urgently required. Independent bodies, informed democratically, need to set research priorities. We also propose that evidence rating schemes are formally modified so research with conflict of interest bias is explicitly downgraded in value.     

Technology‐induced bias in the theory of evidence‐based medicine

Designing trials and studies to minimize confounding and bias is central to evidence‐based medicine (EBM). The widespread use of recent technologies such as machine learning, smartphones, and the World Wide Web to collect, analyse, and disseminate information can improve the efficiency, reliability, and availability of medical research. However, it also has the potential to introduce new sources of significant, technology‐induced evidential bias. This paper assesses the extent of the impact by reviewing some of the methods by and principles according to which evidence is collected, analysed, and disseminated in EBM, supported by specific examples. It considers the effect of personal health tracking via smartphones, the current proliferation of research data and the influence of search engine “filter bubbles”, the possibility of machine learning‐driven study design, and the implications of using machine learning to seek patterns in large quantities of data, for example from observational studies and medical record databases. It concludes that new technology may introduce profound new sources of bias that current EBM frameworks do not accommodate. It also proposes new approaches that could be incorporated in to EBM theory to mitigate the most obvious risks, and suggests where further assessment of the practical implications is needed.     

‘One mission accomplished,more important ones remain’: commentary on Every‐Palmer,S., Howick,J. (2014) How evidence‐based medicine is failing due to biased trials and selective publication. Journal of Evaluation in Clinical Practice, 20 (6), 908–914

Every‐Palmer and Howick suggest that evidence‐based medicine (EBM) is failing in its mission because of contamination of research by manufacturer and researcher‐motivated bias and self‐interest. They fail to define that mission and to distinguish between the EBM movement and the research enterprise it was developed to critique. An educational movement, EBM accomplished its mission to simplify and package clinical epidemiological concepts in a form accessible to clinical learners. Its wide adoption within educational circles fostered critical literacy among several generations of practitioners. Illumination of bias, subterfuge and incomplete reporting of research has been a strength of EBM. Increased uptake and use of clinical research within the health care system properly defines the failing mission that eludes Every‐Palmer and Howick. Responsibility for failure to make progress towards its achievement is shared by virtually all relevant streams within the system, including policy, clinical guideline development, educational movements and the development of approaches to evidence synthesis. Discordance between the epistemological premises pervading today's research and health care community and the complex social processes that ultimately determine research use constitutes an important factor that must be addressed as part of a remedy. Enhanced emphasis on and demonstration of alternative approaches to research such as realism and realist synthesis and the momentum towards development of a learning health care system hold promise as guideposts for the rapidly evolving health care environment.     

Corroborating evidence‐based medicine

Proponents of evidence‐based medicine (EBM) have argued convincingly for applying this scientific method to medicine. However, the current methodological framework of the EBM movement has recently been called into question, especially in epidemiology and the philosophy of science. The debate has focused on whether the methodology of randomized controlled trials provides the best evidence available. This paper attempts to shift the focus of the debate by arguing that clinical reasoning involves a patchwork of evidential approaches and that the emphasis on evidence hierarchies of methodology fails to lend credence to the common practice of corroboration in medicine. I argue that the strength of evidence lies in the evidence itself, and not the methodology used to obtain that evidence. Ultimately, when it comes to evaluating the effectiveness of medical interventions, it is the evidence obtained from the methodology rather than the methodology that should establish the strength of the evidence.     

The need for a rationalist turn in evidence‐based medicine

When evidence‐based medicine (EBM) became established, its dominant rhetoric was empiricist, in spite of rationalist elements in its practice. Exploring some of the key statements about EBM down the years, the paper examines the tensions between empiricism and rationalism and argues for a rationalist turn in EBM to help to develop the next generation of scholarship in the field.     

Failure to place evidence at the centre of quality improvement remains a major barrier for advances in quality improvement

Mondoux and Shojania (M&S) issued a critique of our call to unify all disciplines of relevance for quality improvement (QI). They do not challenge the need for alignment of different fields that have played roles in the QI space. They selected to focus their critique on our views that ultimately the discipline of QI should be based on the principles of evidence‐based medicine (EBM) and decision sciences. In our response, we reaffirm our calls to help achieve needed alignment and integration of all disciplines of importance to QI through “a unifying framework for improving health care” with EBM and decision sciences at helm. Challenging the importance of placing QI on solid empirical basis is misguided: As QI is all about measuring and consequently improving clinical care, acting on reliable evidence must remain its “cornerstone”. Apparent differences in our views appears to be due to our focus on what care should be delivered, while M&S concentrate on how that care should be delivered. The former is the domain of a narrowly defined EBM, while the latter is the realm of improvement/implementation science—which, we argue, should also be evidence‐based. QI initiatives are fundamentally local activities, and regulators would be most helpful if they require each institution to provide an annual plan of its top QI activities not included in the existing mandated list of performance measures. Finally, we addressed a number of specific QI initiatives highlighted by M&S—use of opioids, handwashing, venous‐thromboembolism prophylaxis, hip replacement, and perioperative beta‐blockers—to show that they would have been carried differently if they were based on the principles of EBM. Thus, the failure to place evidence at the centre remains a major barrier for advances in QI.     

Evidence‐based nursing: clarifying the concepts for nurses in practice

Aim. To provide a critical analysis of key concepts associated with evidence‐based nursing (EBN) to substantiate an operational definition for nurses to use in practice. Background. Despite the plethora of literature surrounding what evidence‐based nursing is and is not and how it differs from its cousins, evidence‐based medicine and evidence‐based practice, nurses still struggle to get evidence into practice. Several reasons for this have been reported, for example, a lack of understanding about what evidence‐based nursing means or time to engage with and apply the evidence into practice. Design. An in‐depth critical review and synthesis of literature was undertaken. Method. Using the key words; evidence‐based nursing, evidence‐based medicine and evidence‐based practice 496 articles were yielded. These articles were limited to 83. Using Burns and Grove’s (2001) phased approach to reviewing the literature the articles were critically reviewed and categorised into key concepts and themes. Results. The in‐depth critical review and synthesis of the literature demonstrated that evidence‐based nursing could be defined as a distinct concept. The review clearly shows that for evidence‐based nursing to occur, nurses need to be aware of what evidence‐based nursing means, what constitutes evidence, how evidence‐based nursing differs from evidence‐based medicine and evidence‐based practice and what the process is to engage with and apply the evidence. Conclusion. The in‐depth critical review and synthesis of the evidence‐based nursing literature reinforces the need to consolidate a position for nursing in the evidence‐based field. The review confirms that evidence‐based nursing can be defined and conceptualised; however, for nurses to engage and apply with the evidence‐based processes they need to be informed of what these are and how to engage with them in practice. Relevance to clinical practice. This paper examines the concept of evidence‐based nursing and its application to clinical practice.     

Evidence‐Based Medicine and the Challenge of Low Back Pain: Where Are We Now?

Abstract: Low back pain has long been described as a challenge for both primary care physicians and specialists. Management of low back pain has also been criticized as frequently arbitrary, inappropriate, or ineffective. Contributing factors have been an inadequate evidence base and a need for more rigorous appraisals of the available literature. Evidence‐based medicine, an approach to clinical problem solving, is predicated on the premise that high‐quality health care will result from practices consistent with the best evidence. In contrast to the traditional medical paradigm that placed a heavy reliance on expert opinion, authority, and unsystematic clinical observations, evidence‐based medicine emphasizes the need for rigorous critical appraisals of the scientific literature to inform medical decision making. Evidence‐based medicine places strong weight on the requirement for valid studies, particularly randomized controlled trials, to appropriately evaluate the effectiveness of health care interventions. Because of the rapidly increasing volume of medical literature, however, most clinicians are unable to keep up‐to‐date with all the new data. Two types of preprocessed evidence that can aid busy clinicians in medical decision making are systematic reviews and evidence‐based clinical practice guidelines. Like primary studies, systematic reviews and clinical practice guidelines must adhere to high methodologic standards to reduce error and bias. As in other areas of medicine, the approach to the management of low back pain has been positively affected by the availability of more clinical trials and better use of critical appraisal techniques to evaluate and apply research findings. In addition to more rigorous primary studies, an increasing number of high‐quality systematic reviews and evidence‐based clinical practice guidelines for low back pain are also available. Although some research gaps and methodologic shortcomings persist, the richer evidence base has greatly improved our understanding of what does and does not work for low back pain. Despite these advances, the best available evidence often does not inform everyday clinical decisions for low back pain. Nonetheless, there is widespread agreement that adherence to evidence‐based practice will help improve low back pain patient outcomes and reduce arbitrary variations in care. This article reviews basic principles of evidence‐based medicine, discusses evidence‐based medicine in the context of low back pain management, and summarizes some useful evidence‐based medicine resources.     

Values‐based practice and phenomenological psychopathology: implications of existential changes in depression

Values‐based practice (VBP), developed as a partner theory to evidence‐based medicine (EBM), takes into explicit consideration patients' and clinicians' values, preferences, concerns and expectations during the clinical encounter in order to make decisions about proper interventions. VBP takes seriously the importance of life narratives, as well as how such narratives fundamentally shape patients' and clinicians' values. It also helps to explain difficulties in the clinical encounter as conflicts of values. While we believe that VBP adds an important dimension to the clinician's reasoning and decision‐making procedures, we argue that it ignores the degree to which values can shift and change, especially in the case of psychiatric disorders. VBP does this in three respects. First, it does not appropriately engage with the fact that a person's values can change dramatically in light of major life events. Second, it does not acknowledge certain changes in the way people value, or in their modes of valuing, that occur in cases of severe psychiatric disorder. And third, it does not acknowledge the fact that certain disorders can even alter the degree to which one is capable of valuing anything at all. We believe that ignoring such changes limits the degree to which VBP can be effectively applied to clinical treatment and care. We conclude by considering a number of possible remedies to this issue, including the use of proxies and written statements of value generated through interviews and discussions between patient and clinician.     

The judgements that evidence‐based medicine adopts

In “The evidence that evidence‐based medicine omits”, Brendan Clarke and colleagues argue that when establishing causal facts in medicine, evidence of mechanisms ought to be included alongside evidence of correlations. One of the reasons they provide is that correlations can be spurious and generated by unknown confounding variables. A causal mechanism can provide a plausible explanation for the correlation, and the absence of such an explanation is an indication that the correlation is not causal. Evidence‐based medicine (EBM) proponents remain sceptical about this argument, one problem being that the formulation of a mechanism requires judgements that are external to the evaluation of data and experimental designs—for instance judgements of plausibility against, or derivability from, background knowledge. Because background knowledge is always incomplete and therefore unreliable, EBM proponents maintain that the plausibility of a hypothesis should be evaluated mainly by the quality of population data that yielded it. Here, I use the example of oestrogen replacement therapy's effect on coronary heart disease, an example that is often quoted in defence of the epistemic advantage of randomized controlled trials, to show that the evaluation of the most reliable study design necessarily implies the adoption of judgements that are external to the specific evidence of correlation. The exclusion of evidence of mechanism, therefore, is not effective in bypassing paradigm‐dependent judgements, which are external to specific evidence. Because such judgements cannot be excluded by evidence evaluation, they can only be kept under scrutiny, or adopted uncritically. I propose that the latter option can hinder the maintenance of an active critical inquiry, as well as the analysis of experts' disagreement.     

The hard art of soft science: Evidence-Based Medicine, Reasoned Medicine or both?

In the past 14 years, Evidence-Based Medicine (EBM) has enjoyed unprecedented developments and gained widespread acceptance among health professionals. However, should we be content with producing, critically appraising and using the best evidence available for our understanding of health problems and decision making about them? Are our convictions about EBM's relevance, our conviction and intellectual satisfaction with its mastery and adoption enough? Should we continue pushing forward along this promising path, or should we further diversify the content and scope of EBM? Is EBM the only way to view medicine in the near future? This paper presents some options to choose from in terms of direction and content as well as questions to answer given the current EBM crossroads. More intensive and extensive EBM combined with 'other features'-based medicines may be the preferred strategy to follow in the future to determine the development, use and evaluation of EBM. Argument-based medicine or Reasoned Medicine is one of the options that can be integrated into the mainstream of medical reasoning and decision making.     

循证医学实践与干部医疗保健工作

循证医学实践在临床工作中已取得一定经验，采用循证医学的原理和方法指导干部和老年人群的医疗保健工作是一项全新的课题。不仅对临床医生认识疾病诊治和判断疗效及预后，建立客观合理的健康保健计划具有指导意义。对保健对象获取科学先进的预防保健知识，认知疾病治疗目标和预后，避免不合理和不必要的医疗负荷具有重要意义。同时对卫生行政部门的医疗保健决策也有一定的参考意义。     

Therapist self‐disclosure and the problem of shared‐decision making

Therapist self‐disclosure is one of the most controversial topics in the history of psychotherapy. The controversies reflect some basic discussions regarding the nature of psychotherapy practice. In psychotherapy practice, a particular concern is the interaction between the psychotherapist and the patient. The expert‐patient interaction has been addressed in a novel framework for clinical practice called shared‐decision making. In this paper, we discuss the relationship between self‐disclosure and shared‐decision making. The chief aim is to illustrate some of the principles and practical problems with shared‐decision making by using therapist self‐disclosure as an example.     

Shared decision‐making in mental and behavioural health interventions

Elements of shared decision‐making (ie, collaboration, patient preferences, and working alliance) have long been discussed and studied in the field of clinical psychology; however, research indicates that shared decision‐making is not typically used in clinical practice. Instead, clinicians often rely on a paternalistic approach. In this article, we provide a narrative review of the existing research supporting shared decision‐making for mental and behavioural health concerns, we discuss several barriers that impede its use in actual clinical practice, and we provide recommendations for increasing shared decision‐making when working with patients.