Conceptual and Methodological Pitfalls in Experimental Studies: An Overview, and the Case of Alzheimer's Disease.

Daniela Puzzo,Fiorenzo Conti

doi:10.3389/fnmol.2021.684977

Abstract

The main goal of scientific research is to uncover new knowledge to understand reality. In the field of life sciences, the aim of translational research—to transfer results “from bench to bedside”—has to contend with the problem that the knowledge acquired at the “bench” is often not reproducible at the “bedside,” raising the question whether scientific discoveries truly mirror the real world. As a result, researchers constantly struggle to overcome the dichotomy between methodological problems and expectations, as funding agencies and industries demand expandable and quick results whereas patients, who are uninterested in the epistemological dispute, only ask for an effective cure. Despite the numerous attempts made to address reproducibility and reliability issues, some essential pitfalls of scientific investigations are often overlooked. Here, we discuss some limitations of the conventional scientific method and how researcher cognitive bias and conceptual errors have the potential to steer an experimental study away from the search for the vera causa of a phenomenon. As an example, we focus on Alzheimer’s disease research and on some problems that may have undermined most of the clinical trials conducted to investigate it.

Highlights

Translational or “bench to bedside” research aims to transfer knowledge from basic science to clinical practice
The whole process depends on the validity of the experimental approach itself, since besides the objective risks and intrinsic difficulties of the bench to bedside transition (Seyhan, 2019), methodological and, more frequently, interpretive mistakes may lead to falls in crossing the “valley of death” (Llovera and Liesz, 2016)
Results cannot be replicated in different models

Summary

Introduction

Translational or “bench to bedside” research aims to transfer knowledge from basic science to clinical practice. As theorized by Claude Bernard, the founder of Experimental Medicine (Conti, 2001, 2002), the process starts with understanding how a physiological system works and tries to uncover the pathophysiology of a disease in order to diagnose, prevent and cure it. In translational research the challenge and pressure are felt especially keenly, considering the expectations of clinical application and their public health implications. To prevent the failure of the translation process, several studies have examined the main confounding factors that might invalidate an experimental study (see Table 1), focusing on result reproducibility and reliability (e.g., National Academies of Sciences, Engineering, and Medicine (NASEM)., 2019). In life sciences the issue of the scientific method is often dismissed, based on the widespread belief of the existence of only one, undoubtedly correct method (Wagensberg, 2014)

Methods

Results

Conclusion