Barbara Osimani

Until RCT proven? On the asymmetry of evidence requirements for risk assessment

The problem of collecting, analysing and evaluating evidence on adverse drug reactions is an example of the more general class of epistemological problems related to scientific inference and prediction, as well as a central problem of health care practice. Philosophical discussions have analysed critically the methodological pitfalls and epistemological implications of evidence assessment in medicine; however, they have focused predominantly on evidence of treatment efficacy. Most of this work is devoted to statistical methods of causal inference with a special focus on the privileged role assigned to randomized controlled trials (RCTs) in evidence-based medicine. Regardless of whether the RCTs privilege holds for efficacy assessment, it is nevertheless important to make a distinction between causal inference in relation to intended and unintended effects, in that the unknowns at stake are heterogeneous in the two contexts. This point has been emphasized by epidemiologists in the last decade. Their primary focus is methodological and regards the fact that bias and confounding factors do not affect studies on intended and unintended effects in the same way. However, deeper concerns ground the intuition for such a distinction; these are related to the constraints we impose on evidence and their epistemological justification. My thesis is that such constraints ought to be understood as being different in evidence for risk versus for efficacy. I present the recent debate on the causal association between acetaminophen and asthma in order to illustrate the point at issue. The upshot of my analysis is that different epistemologies confer different methodological choices, which in turn bring about relevant practical implications such as the decision to restrict or suspend drug use rather than leaving it on the market. Thus, it is worth considering the criteria underlying our evidence constraints because they may be ill suited to the purpose for which they are used.

The precautionary principle in the pharmaceutical domain: a philosophical enquiry into probabilistic reasoning and risk aversion

Pharmaceutical decisions are affected by several forms of uncertainty, which are sharpened both by the high stakes at play and by the complexity of the epistemological procedures needed to provide the necessary information to make these decisions. The precautionary principle as applied to pharmaceutical decisions through the notion of ‘well-founded suspicion’ takes into account one special sort of these uncertainties: the uncertainty concerning the causal connection between observed adverse reactions and the drug suspected of causing these effects. Commentators have criticised the precautionary principle for its inhibitory action on innovation and research, for its unjustified imbalance towards the risk produced by human agency versus natural risks; and from a formal point of view, for its vagueness and unsystematic application. Their criticisms have generally been grounded in the supposed risk-aversive nature of the precautionary principle. The purpose of this article is to address these criticisms. In this article, Iengage in a discussion of the current methodological debate about epistemic asymmetries concerning standards of evidence for pharmaceutical harm and benefits to examine the rationale underpinning the logic of the precautionary principle. I show that the precautionary principle has been developed as a means of acknowledging uncertainty, and therefore, the basis of its implementation should be based on inductive rather than deductive approaches to scientific enquiry.

Pharmaceutical risk communication: sources of uncertainty and legal tools of uncertainty management

The purpose of this article is to differentiate between the different functions of pharmaceutical risk communication and make explicit their different legal natures and implications. Risk communication has been generally categorised as a warning act, which is performed in order to prevent or minimise risk. Risk analysis has also drawn attention to the role played by information in reducing uncertainty about risk. Both approaches focus on the safety aspects of communication and its role in harm reduction. However, there are cases where a risk cannot be avoided or uncertainty reduced, for example the side effects associated with pharmaceutical products or when a decision about drug approval or withdrawal has to be made on the basis of available evidence. In these instances, risk communication has other purposes than preventing risk or reducing uncertainty. This article analyses the legal instruments which have been developed to control and manage the risks related to drugs (such as the notion of ‘development risk’ or ‘residual risk’) and relates them to different kinds of uncertainty. These are conceptualised as epistemic, ecological, metric, ethical and stochastic, depending on their nature. By referring to this taxonomy, different functions of pharmaceutical risk communication are identified and connected with the legal tools of uncertainty management.

Causal Assessment of Pharmaceutical Treatments: Why Standards of Evidence Should not be the Same for Benefits and Harms?

It is increasingly acknowledged both among epidemiologists and regulators that the assessment of pharmaceutical harm requires specific methodological approaches that cannot simply duplicate those developed for testing efficacy. However, this intuition lacks sound epistemic bases and delivers ad hoc advice. This paper explains why the same methods of scientific inference do not fare equally well for efficacy and safety assessment by tracing them back to their epistemic foundations. To illustrate this, Cartwright’s distinction into clinching and vouching methods is adopted and a series of reasons is provided for preferring the latter to the former: (1) the need to take into account all available knowledge and integrate it with incoming data; (2) the awareness that a latent unknown risk may always change the safety profile of a given drug (precautionary principle); (3) cumulative learning over time; (4) requirement of probabilistic causal assessment to allow decision under uncertainty; (5) impartiality; and (6) limited and local information provided by randomised controlled trials. Subsequently, the clinchers/vouchers distinction is applied to a case study concerning the debated causal association between paracetamol and asthma. This study illustrates the tension between implicit epistemologies adopted in evaluating evidence and causality; furthermore, it also shows that discounting causal evidence may be a result of unacknowledged low priors or lack of valid alternative options. We conclude with a presentation of the changing landscape in pharmacology and the trend towards an increased use of Bayesian tools for assessment of harms.

Revision of International Classification of Functioning, Disability and Health ethical guidelines: International Classification of Functioning, Disability and Health-related ethical issues.

Colombetti E, Osimani B, Aluas M, Pessina A, Musio A: Revision of international classification of functioning, disability and health ethical guidelines: international classification of functioning, disability and health-related. Am J Phys Med Rehabil 2012;91(suppl):S155YS158.

Disability, Human Rights, and the International Classification of Functioning, Disability, and Health Systematic Review

ABSTRACTThis literature review focuses on the literature on disability from the ethical and human rights perspective in the light of the International Classification of Functioning, Disability, and Health in the period from January 1, 2008, to June 30, 2010. This article identifies and examines studies that deal with the subject of disability with reference to rights, ethical issues, and justice. A total of 42 articles and 33 books were selected. The subject most frequently dealt with in studies on disability is that of human rights (76% of the articles and 79% of the books examined), followed by topics relating to welfare (52% of articles and 64% of books), International Classification of Functioning, Disability, and Health (38% of articles and 45% of books), justice (24% of articles and 48% of books), education (21% of articles and 61% of books), and work (19% of articles and 39% of books). The subject of disability is dealt with in various fields of study and various disciplines. Most of the studies are based on the legal approach. It is to be hoped that there will be an increase in the philosophical and ethical study of disability, which has only recently entered the European debate.

Is genetic information family property? Expanding on the argument of confidentiality breach and duty to inform persons at risk

A current trend in bioethics considers genetic information as family property. This paper uses a logical approach to critically examine Matthew Liao’s proposal on the familial nature of genetic information as grounds for the duty to share it with relatives and for breach of confidentiality by the geneticist. The authors expand on the topic by examining the relationship between the arguments of probability and the familial nature of genetic information, as well as the concept of harm in the context of genetic risk. Lastly, they examine the concept of harm in relation to the type of situations w the potential recipient of the information is not the person directly affected by the risk.A current trend in bioethics considers genetic information as family property. This paper uses a logical approach to critically exami - ne Matthew Liao’s pro...

¿LA INFORMACIÓN GENÉTICA ES DE PROPIEDAD FAMILIAR? AMPLIANDO EL ARGUMENTO DE LA RUPTURA DE LA CONFIDENCIALIDAD Y EN EL DEBER DE INFORMAR PERSONAS EN SITUACIÓN DE RIESGO

A current trend in bioethics considers genetic information as family property. This paper uses a logical approach to critically examine Matthew Liao’s proposal on the familial nature of genetic information as grounds for the duty to share it with relatives and for breach of confidentiality by the geneticist. The authors expand on the topic by examining the relationship between the arguments of probability and the familial nature of genetic information, as well as the concept of harm in the context of genetic risk. Lastly, they examine the concept of harm in relation to the type of situations w the potential recipient of the information is not the person directly affected by the risk.A current trend in bioethics considers genetic information as family property. This paper uses a logical approach to critically exami - ne Matthew Liao’s pro...

A INFORMAÇÃO GENÉTICA É DE PROPRIEDADE FAMILIAR? AMPLIANDO O ARGUMENTO DA QUEBRA DA CONFIDENCIALIDADE E O DEVER DE INFORMAR PESSOAS EM SITUAÇÃO DE RISCO

A current trend in bioethics considers genetic information as family property. This paper uses a logical approach to critically examine Matthew Liao’s proposal on the familial nature of genetic information as grounds for the duty to share it with relatives and for breach of confidentiality by the geneticist. The authors expand on the topic by examining the relationship between the arguments of probability and the familial nature of genetic information, as well as the concept of harm in the context of genetic risk. Lastly, they examine the concept of harm in relation to the type of situations w the potential recipient of the information is not the person directly affected by the risk.A current trend in bioethics considers genetic information as family property. This paper uses a logical approach to critically exami - ne Matthew Liao’s pro...

Safety vs. efficacy assessment of pharmaceuticals: Epistemological rationales and methods

In their comparative analysis of Randomised Clinical Trials and observational studies, Papanikoloau et al. (2006) assert that “it may be unfair to invoke bias and confounding to discredit observational studies as a source of evidence on harms”. There are two kinds of answers to the question why this is so. One is based on metaphysical assumptions, such as the problem of causal sufficiency, modularity and other statistical assumptions. The other is epistemological and relates to foundational issues and how they determine the constraints we put on evidence. I will address here the latter dimension and present recent proposals to amend evidence hierarchies for the purpose of safety assessment of pharmaceuticals; I then relate these suggestions to a case study: the recent debate on the causal association between paracetamol and asthma. The upshot of this analysis is that different epistemologies impose different constraints on the methods we adopt to collect and evaluate evidence; thus they grant “lower level” evidence on distinct grounds and at different conditions. Appreciating this state of affairs illuminates the debate on the epistemic asymmetry concerning benefits and harms and sets the basis for a foundational, as opposed to heuristic, justification of safety assessment based on heterogeneous evidence.