Mapping the ethical landscape of digital biomarkers: A scoping review.

In the evolving landscape of digital medicine, digital biomarkers have emerged as a transformative source of health data, positioning them as an indispensable element for the future of the discipline. This necessitates a comprehensive exploration of the ethical complexities and challenges intrinsic to this cutting-edge technology. To address this imperative, we conducted a scoping review, seeking to distill the scientific literature exploring the ethical dimensions of the use of digital biomarkers. By closely scrutinizing the literature, this review aims to bring to light the underlying ethical issues associated with the development and integration of digital biomarkers into medical practice.

Current trials in erythropoietic protoporphyria: are placebo controls ethical?

A new active substance called "dersimelagon" (MT-7117) is being tested as an alternative treatment option for Erythropoietic protoporphyria (EPP). At the moment, dersimelagon is being tested both in the US and in Europe in a phase III placebo-controlled RCT. However, given the availability of an already approved treatment option for EPP the use of a placebo arm is questionable from an ethics point of view. We analyze the issue and suggest that a noninferiority active-control trial without placebo is an ethically and scientifically more valid design to test the efficacy of dersimelagon as well as other EPP treatments.

Accelerated drug approval: Meeting the ethical yardstick.

Drugs addressing unmet medical needs can change the lives of millions. Developing and validating new drugs can, however, take many years. To streamline the assessment of new drugs, regulatory agencies have long established shortened review pathways. Among these programs, Accelerated Approval (AA) has recently come under scrutiny due to the U.S. Food and Drug Administration's decision to authorize Aducanumab, the first Alzheimer's disease drug. This decision attracted fierce criticism due to the allegedly insufficient evidence about the safety and efficacy of the drug. While considerable scholarly attention has been devoted to this case, the ethical aspects of the AA regulatory pathway have so far remained relatively unexplored. In this paper, we set out to fill this gap. We illustrate six conditions that should be met for AA to be ethically acceptable: moral solicitude, evidence, risk mitigation, impartiality, sustainability, and transparency. We discuss such conditions and suggest practical steps to implement them in regulatory and oversight processes. Taken together, our six conditions represent a benchmark for assessing the ethical validity of AA processes and decisions.

A defense of surgical procedures regulation.

Since the advent of drug regulation in 1962, regulatory agencies have been in the practice of using strict standards to test the safety and efficacy of medical treatments and products. Regulatory agencies, such as the FDA, demand two full-fledged Randomized Clinical Trials demonstrating the safety and effectiveness of drugs to grant its marketing authorization. On the contrary, surgical treatments are left completely unregulated. There are several reasons explaining this difference, and all of them point to the difficulty of conducting well-designed RCTs in surgery. However, we argue that none of these arguments is decisive and that, under certain conditions, surgical RCTs can be morally justified and methodologically sound. Although ethical constraints restrict the number of testable surgical procedures, and surgical trials might not be as dependable as pharmaceutical RCTs, our analysis suggests that, in certain cases, it is possible to obtain high-quality evidence about the safety and efficacy of surgical procedures. Untested surgical treatments may prove to be ineffective and harm patients. Therefore, regulation of surgical procedures seems not only morally acceptable and able to provide reliable scientific evidence, but also desirable and justified from an ethical-political standpoint.

Genuine versus bogus scientific controversies: the case of statins.

Science progresses through debate and disagreement, and scientific controversies play a crucial role in the growth of scientific knowledge. However, not all controversies and disagreements are progressive in science. Sometimes, controversies can be pseudoscientific; in fact, bogus controversies, and what seem like genuine scientific disagreements, can be a distortion of science set up by non-scientific actors (e.g., interest groups). Bogus controversies are detrimental to science because they can hinder scientific progress and eventually bias science-based decisions. The first goal of this paper is to elucidate the distinction between bogus and genuine scientific controversies and provide a qualitative methodology, based on the literature on expertise, for distinguishing between the two. We will illustrate six epistemic criteria for distinguishing bogus from genuine scientific debates in science and medicine. This heuristic strategy applies directly to scientific reports, and it relies mostly on the social structure of science. We will then apply the above criteria to a case study: the controversy over statins, which are widely prescribed drugs for reducing the level of cholesterol and preventing cardiovascular disease.

More Than One Way to Measure? A Casuistic Approach to Cancer Clinical Trials.

Testing new oncological treatments in the era of personalized medicine is raising many challenges to the current regulatory paradigm. In particular, randomized controlled trials (RCTs) have proved to be inadequate for testing targeted therapies. Nonetheless, the Food and Drug Administration (FDA) still requires them to grant market approval. This article questions the idea that regulatory decision-making can be reduced to sound statistical inferences. The author discusses the implications of tumor heterogeneity for regulatory assessment of new medications, considering the challenges that the current paradigm is facing and addressing criticisms that could explain its resistance to change. To overcome those criticisms, the author proposes implementing casuistic method into regulatory decision-making.

[Reliability of biomedical research.] / L'affidabilità della ricerca biomedica. La crisi della replicabilità.

In the last century, use of statistics became widespread in biomedical research, making medicine more scientific. However, the misuse of statistical methods may have a negative impact on the reproducibility of experiments, which instead should be at the core of scientific method. The consequence is the so called "replicability crisis", which can affect the reliability of scientific results: if one cannot replicate a published finding, she would hardly trust it. In this paper, firstly, we will provide a short review of the replicability crisis. Indeed, this issue has recently drawn the attention of the entire scientific community. Secondly, we will try to figure out some potential explanation for this phenomenon. Finally, we will show how this problem deeply affects also the reliability of randomized clinical trial, which is fundamental for the medical and regulatory decision-making.