robustness of molecular biomarker development has the ability to conduct proof--

of-concept studies for delineating the pathways involved in particular disease for

targeted therapies and personalised medicine. The outcome has a narrow focus on

the discovery of individual biomarkers to search for genetic variation in patients

and development of personalised/precision medicines.

Keywords

Biomarkers · Precision medicine · Repurposed drugs · Drug discovery ·

Diagnostics · Targeted delivery

9.1

Introduction

The process of drug discovery and development continues to be slow, risk-laden,

inefficient and costly and is delivering result products of questionable value in terms

of efficacy and safety through translational research approach (benchtop to bedside)

(Cook et al. 2014). The translational approach in research generally begins with the

conception of ideas to solve the identified problems. It is the process of applying

discoveries generated during research in the laboratory, through preclinical studies,

to the clinical trials for providing new drugs in the market (Woolf 2008; Carini et al.

2019). It forms a connecting link between basic research/applied science and clinical

research (Cohrs et al. 2015; Fyfe 2019). However, the outcome of translational

research into a fruitful therapeutic entity is many a times insufficient when the results

are interpreted in terms of the clinical impact (Ashburn and Thor 2004; Scannell

et al. 2012).

The cumulative risk associated with translational drug discovery approach to bring

a new drug to market lies in the failure rate of a drug candidate at each stage of clinical

trial, i.e. 46% during Phase I, 66% in Phase II and 30% in Phase III (Paul et al. 2010). It

is estimated that 12–15 years and capitalised cost of approximately $2.87 billion are

required from drug discovery to product launch (DiMasi et al. 2016). It is pertinent to

note that besides the high budget, it majorly suffers with the additional detrimental

factors such as high attrition rates mostly during the middle of the project. The metrics

associated with the drug discovery and development process are clearly of concern and

eye-watering. The most feared outcome is the therapeutic failure and value proposition

of marketed drug products produced through benchtop-to-bedside research (Carvalho

et al. 2014; Waring et al. 2015; Waring and Naylor 2016).

Contrary to the conventional benchtop-to-bedside research being used for the

drug discovery, the reverse translational approach (bedside-to-benchtop research),

generally based on the data collection on a real-time basis, starts with the factual

studies covered by the real-life patient experiences present in the clinic. The said

mechanism of research usually works in an opposite direction to understand the

mechanism and experiences observed by the patients. Here, the therapeutic failure

represents an opportunity to identify new therapeutic targets and novel biomarkers of

drug response. Thus, in the reverse translation paradigm, research becomes a

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R. K. Goyal and G. Aggarwal