Smarter Metrics for Smarter Medicine: Reinventing Outcome Rankings
A Worrying Context A 2018 prospective study, IATROSTAT , conducted by the French network of pharmacovigilance centres, reveals a concerning rise in hospital admissions caused by adverse drug reactions (ADRs). Commissioned by the French National Agency for Medicines and Health Products Safety (ANSM), the study also examined whether such incidents could have been prevented. According to the findings, 8.5% of hospitalised patients were admitted due to an ADR, with a mortality rate of 1.3% among those cases. Alarmingly, in 16% of these instances, the ADRs could have been avoided. These preventable cases typically involved the use of medications in a manner inconsistent with either the product’s official summary of characteristics (SmPC) or established clinical guidelines issued by medical societies. By extrapolating the data, researchers estimate that approximately 212,500 hospital admissions occur annually in France due to ADRs, leading to around 2,760 deaths each year. The controversy surrounding side effects is fueled by the difficulty of assessing and clearly communicating risks, the societal perception of the benefit-risk balance, and the rise of the precautionary principle. Some side effects are accepted when their occurrence is outweighed by a significant benefit, but this acceptance depends on the context, the severity of the illness, the transparency of the information, and the level of trust in the healthcare system. The is all the more relevant for CNS treatments, knowing that 60% of patients do not adhere to their treatments (meaning that the drug has either no efficacy or conducts to adverse effects). The Requip case clearly illustrates the dilemmas faced by doctors, patients, and health authorities: this medication, prescribed for Parkinson’s disease, is highly effective in most cases but can cause serious side effects in some patients, such as hypersexuality or gambling addiction. For Antoine Béguin and Dr. Irène Frachon, authors of the book Effets secondaires : le scandale français ( Side Effects: The French Scandal ), the issue is not to question the usefulness of such treatments, but to denounce the lack of transparency when it comes to side effects and proper information. Improving the win-ratio for precision medicine To tackle the benefit risk issue regarding adverse effects, the Win Ratio was introduced in 2012 as a new method for examining composite endpoints and has been recommended by the FDA and EMA to analyze hierarchical and multiple outcomes in clinical trials. Originally, the Win Ratio involves pairing two patients: patient A receives the treatment, while patient B does not. The outcomes for both are then compared, and this is referred to as the causal treatment effect. The causal treatment effect is defined as the difference between what would have happened to a person with the treatment and what would have happened to that same person without the treatment. Therefore, in heterogeneous populations (where patients differ greatly (be it by gender, ethnicity, age, comorbidities), the Win Ratio can lead to misleading conclusions about the effectiveness of the treatment. This highlights a major limitation of the current Win Ratio: the two patients being compared may differ significantly in their characteristics, making the results less generalizable to the broader population. One approach to address this issue is to form groups of patients that are as homogeneous as possible. Dr. Mathieu Evens, researcher at Inria Montpellier and Theremia, proposes a new way to measure the effects by creating a new measure of individual causal effect called the Nearest Neighbor Pairing: each treated patient is matched with the most similar control patient (based on observed variables). This approach allows for a better estimation of a causal effect. It can be seen as an extreme form of stratification,where individuals who are very similar are grouped together. Want to read the full article ? Click here https://arxiv.org/abs/2501.16933
