Question based drug development is sometimes referred to as drug development 2.0. This is a modern approach of drug development, which allows researchers to for example obtain substantial information concerning the drug or therapy in development early on. 

However, some may ask why is drug development 2.0 is needed. First, let’s look into some problems in the current drug development phases:  

• Yearly, 200 000 compounds are screened on potential medicinal properties worldwide, however about only twenty new drugs are eventually introduced each year.  

• The discovery and development of new medicines is an expensive and time-consuming process. This rigorous process takes an average of 10-15 years to discover and develop a new medicine, with most of the time spent focusing on testing the drug’s safety.  

• Drug development is costly. The average cost of bringing one new medicine to the market is several hundreds of millions. But if you also include all 'indirect costs' (e.g. cost of failed drugs, 'capitalized costs', etc.) a large study ('Tuft study') estimates it could well be estimated at $2.5 billion. 

Recent studies have shown that the amount of money pharmaceutical industries spend on research and development of new drugs keeps rising over the years, while the number of new compounds approved decreases. This implies that these companies need to rely on a few highly successful products in order to fund the high costs of innovative research and development (R&D)

The question-based approach is designed to make main issue in drug development projects explicit rather than implicit. This main issue can be described briefly as “Are all the questions asked and, most importantly, answered adequately?  If so, a regulatory authority can confidently give market authorization. During the whole drug development period, project managers can monitor the progress of the study by the questions that have been answered and the length of the remaining list. Note that one question can be answered with different studies and one study can provide partial answers to multiple questions. 

So, what are these questions?  

During the classical phases 1 to 3 (and 4), a number of generic questions have to be answered: 

1) Does the biologically active compound/active metabolites get to the site of action?  

Issues that should be determined by answering this question concerns the absorption, distribution, metabolism and excretion of the drug and possible active metabolites. Additionally, properties such as the ability to penetrate the blood-brain-barrier should be determined for central nervous system (CNS) active drugs. Biologically active metabolites that are unexpectedly formed in vivo or the discovery of unexpected sites of action should be incorporated in this main question as soon as observed.  

2) Does the compound cause its intended pharmacological/ functional effect(s)?  

Answering this question includes a demonstration of the mechanism of action of the investigational drug.  

3) Does the compound have beneficial effects on the disease or its pathophysiology? 

This question is to establish the effects on the disease but also the alteration of other physiological systems resulting in clinical side-effects. This question further mirrors the question traditionally answered in the classical phase 3 studies.  

4) What is the therapeutic window of the new drug? 

In order to select an optimal dosing that is efficacious at tolerated levels, the therapeutic window of each investigational drug needs to be determined. This question focuses on this topic and includes important sub-questions that will aid in determining the therapeutic window, like: Which dose regimen will keep the drug’s concentration within the therapeutic window? What is the optimal dosing interval relative to the intended indication (chronicity of intended drug exposure)?

5) How do the sources of variability in drug response in the target population affect the development of the product?  

The sources of variability in drug response have been defined as:  

·   Dose (Formulations and compliance)  

·   Pharmacokinetics: what the body does to the drug  (Absorption, distribution, metabolism and elimination (ADME))

·   Pharmacodynamics: what the drug does to the body (Sensitivity, maximum response, etc)

The main question in this section should include: Are there any specific factors in the target population that may affect dosage?

Furthermore, general sub-questions could arise, like Is there any food-interaction with this compound?