Dispositions and Causality Assessment in Pharmacovigilance: Proposing the Dx3 Approach for Assessing Causality with Small Data Sets.

A new approach is proposed for assessing causality in pharmacovigilance. The Dx3 approach is designed to qualitatively evaluate three types of dispositions when assessing whether a particular medicine has or could have caused a certain adverse event. These are: the drug disposition; the pre-disposition of the patient taking the drug (vulnerability) and; the disposition of the patient-drug interaction (mutuality). Each of these three types of dispositions will represent valuable causally relevant evidence for assessing a potential signal of harm. A checklist is provided to guide the assessment of causality for both single individual case safety reports (ICSRs) and case series. Different types of causal information are ranked according to how well suited they are for establishing a disposition. Two case examples are used to demonstrate how the approach can be used in practice for assessment purposes. One aim of the approach is to offer a qualitative way to assess causality and to make the reasoning of different assessors more transparent. A second aim is to encourage the collection of more qualitatively rich patient narratives in the ICSRs. Crucially, we believe this approach can support the inclusion of the single ICSR as a valid and valuable form of evidence.

Erice Call for Change: Utilising Patient Experiences to Enhance the Quality and Safety of Healthcare.

This 'Erice Call for Change' is a report from a group of experts, patients and patient representatives who met in Erice in September 2019 following previous similar meetings after the original Erice Declaration (1996). The aim of the meeting was to discuss the challenge of causal complexity and individual variation in modern healthcare. The group's concern was the impact that new clinical decision-making tools, based on statistical correlations in large databases, could have on individual patient care if they replace other types of clinical investigation and knowledge. The group calls for a change in the approach to the care of the individual patient, and indicates some specific challenges to overcome for such changes to happen.

Causal Evidence and Dispositions in Medicine and Public Health.

Since the introduction of evidence-based medicine, there have been discussions about the epistemic primacy of randomised controlled trials (RCTs) for establishing causality in medicine and public health. A growing movement within philosophy of science calls instead for evidential pluralism: that we need more than one single method to investigate health outcomes. How should such evidential pluralism look in practice? How useful are the various methods available for causal inquiry? Further, how should different types of causal evidence be evaluated? This paper proposes a constructive answer and introduces a framework aimed at supporting scientists in developing appropriate methodological approaches for exploring causality. We start from the philosophical tradition that highlights intrinsic properties (dispositions, causal powers or capacities) as essential features of causality. This abstract idea has wide methodological implications. The paper explains how different methods, such as lab experiments, case studies, N-of-1 trials, case control studies, cohort studies, RCTs and patient narratives, all have some strengths and some limitations for picking out intrinsic causal properties. We explain why considering philosophy of causality is crucial for evaluating causality in the health sciences. In our proposal, we combine the various methods in a temporal process, which could then take us from an observed phenomenon (e.g., a correlation) to a causal hypothesis and, finally, to improved theoretical knowledge.

Philosophical bias is the one bias that science cannot avoid.

Scientists seek to eliminate all forms of bias from their research. However, all scientists also make assumptions of a non-empirical nature about topics such as causality, determinism and reductionism when conducting research. Here, we argue that since these 'philosophical biases' cannot be avoided, they need to be debated critically by scientists and philosophers of science.

From Ideal to Real Risk: Philosophy of Causation Meets Risk Analysis.

A question has been raised in recent years as to whether the risk field, including analysis, assessment, and management, ought to be considered a discipline on its own. As suggested by Terje Aven, unification of the risk field would require a common understanding of basic concepts, such as risk and probability; hence, more discussion is needed of what he calls "foundational issues." In this article, we show that causation is a foundational issue of risk, and that a proper understanding of it is crucial. We propose that some old ideas about the nature of causation must be abandoned in order to overcome certain persisting challenges facing risk experts over the last decade. In particular, we discuss the challenge of including causally relevant knowledge from the local context when studying risk. Although it is uncontroversial that the receptor plays an important role for risk evaluations, we show how the implementation of receptor-based frameworks is hindered by methodological shortcomings that can be traced back to Humean orthodoxies about causation. We argue that the first step toward the development of frameworks better suited to make realistic risk predictions is to reconceptualize causation, by examining a philosophical alternative to the Humean understanding. In this article, we show how our preferred account, causal dispositionalism, offers a different perspective in how risk is evaluated and understood.

What is the guidelines challenge? The CauseHealth perspective.

This paper is an introduction to the conference, The Guidelines Challenge, held in Oxford in October 2017. My aim is to explain our motivation for organising this conference, as part of the research project Causation, Complexity, and Evidence in Health Sciences (CauseHealth). Depending on the professional starting point, the guidelines challenge can be interpreted in a number of ways. Our idea with this conference was to discuss guidelines from 3 overarching perspectives: practice, policy, and philosophy. In particular, we wanted to discuss some of the challenges that face anyone developing and implementing clinical guidelines in the evidence-based era of medicine. This introduction gives a brief overview of what CauseHealth sees as the guidelines challenge from these perspectives. More attention is given to the philosophical issues with which the CauseHealth project is particularly concerned, although a proper treatment or discussion of these issues naturally falls outside the scope of this introduction.

A philosophical argument against evidence-based policy.

RATIONALE, AIMS AND OBJECTIVES: Evidence-based medicine has two components. The methodological or ontological component consists of randomized controlled trials and their systematic review. This makes use of a difference-making conception of cause. But there is also a policy component that makes a recommendation for uniform intervention, based on the evidence from randomized controlled trials. METHODS: The policy side of evidence-based medicine is basically a form of rule utilitarianism. But it is then subject to an objection from Smart that rule utilitarianism inevitably collapses. If one assumes (1) you should recommend the intervention that has brought most benefit (the core of evidence-based policy making), (2) individual variation (acknowledged by use of randomization) and (3) no intervention benefits all (contingent but true), then the objection can be brought to bear. CONCLUSIONS: A utility maximizer should always ignore the rule in an individual case where greater benefit can be secured through doing so. In the medical case, this would mean that a clinician who knows that a patient would not benefit from the recommended intervention has good reason to ignore the recommendation. This is indeed the feeling of many clinicians who would like to offer other interventions but for an aversion to breaking clinical guidelines.

At the borders of medical reasoning: aetiological and ontological challenges of medically unexplained symptoms.

Medically unexplained symptoms (MUS) remain recalcitrant to the medical profession, proving less suitable for homogenic treatment with respect to their aetiology, taxonomy and diagnosis. While the majority of existing medical research methods are designed for large scale population data and sufficiently homogenous groups, MUS are characterised by their heterogenic and complex nature. As a result, MUS seem to resist medical scrutiny in a way that other conditions do not. This paper approaches the problem of MUS from a philosophical point of view. The aim is to first consider the epistemological problem of MUS in a wider ontological and phenomenological context, particularly in relation to causation. Second, the paper links current medical practice to certain ontological assumptions. Finally, the outlines of an alternative ontology of causation are offered which place characteristic features of MUS, such as genuine complexity, context-sensitivity, holism and medical uniqueness at the centre of any causal set-up, and not only for MUS. This alternative ontology provides a framework in which to better understand complex medical conditions in relation to both their nature and their associated research activity.

Causation and evidence-based practice: an ontological review.

This paper explores the nature of causation within the framework of evidence-based practice (EBP) for health care. The aims of the paper were first to define and evaluate how causation is presently accounted for in EBP; second, to present an alternative causal account by which health care can develop in both its clinical application and its scientific research activity. The paper was premised on the idea that causation underlies medical and health care practices and impacts on the way we understand health science research and daily clinical practice. The question of what causation is should therefore be of utmost relevance for all concerned with the science, philosophy and progress of EBP. We propose that the way causation is thought of in contemporaneous health care is exposed by evidential frameworks, which categorize research methods on their epistemological strengths. It is then suggested that the current account of causation is limited in respect of both the functionality of EBP, and its inherent scientific processes. An alternative ontology of causation is provided, which has its roots in dispositionalism. Here, causes are not seen as regular events necessitating an effect, but rather phenomena that are highly complex, context-sensitive and that tend towards an effect. We see this as a better account of causation for evidence-based health care.