A clinical trial or clinical study is defined as any investigation in human subjects intended to discover or verify the clinical, pharmacological, and/or other pharmacodynamic effects of an investigational product, and/or to identify any adverse reactions to an investigational product, and/or to study absorption, distribution, metabolism, and excretion of an investigational product with the objective of ascertaining its safety and/or efficacy. While the major questions answered are those of clinical value in all three phases, economic end-points and strategic end-points like quality of life (QoL) are introduced during Phases II and III. It is not uncommon that these economic and strategic end-points are introduced in earlier phases as well.
In Evidence-Based Medicine (EBM), evidence for drug is shown through clinical and research studies and the evidence includes the clinical value and comparative effectiveness of the drug. On the other hand, in Value-Based Medicine (VBM), BioPharma companies are required to show the economic and strategic value (indirect economic value) of the drug as part of evidence in addition to the clinical value of the drug. VBM is critical as many stakeholders seek this information to make decisions regarding product access, utilization, advocacy, and policy.
Value-Based Study Design: As the name implies, value-based study design revolves around designing the clinical study to generate the required evidence and value of the product to maximize its commercial potential. The VBS design revolves around generating evidence as envisioned in the Drug Value Profile. The VBS design has three main components:
Study Design Endpoints: The most important part of study design is being able to develop realistic and achievable primary and secondary end-points to show value and to achieve differentiation. As an example, in cancer trials, the “overall survival” can be a primary endpoint and “progression free survival” can be a secondary endpoint. Both secondary research and expert advice must be leveraged to develop compelling end-points as the drug’s ultimate perceived value by different stakeholders when approval is directly linked to these end-points.
Study Design: The next step is to define the type of study that is required (e.g., randomized, non-randomized, single/double-blinded) to generate adequate evidence for the safety and efficacy of the drug; the dosage and dosage regimen of the drug including dosage form, duration, and routes of administration, packaging, and labeling; and the optimal size of study subjects required to ensure that the results will be statistically significant. Additionally, the number of sites where the clinical trials will be conducted also have to be determined and accordingly identified. .
Study Protocols: The final step is to define the protocols, inclusive of subject inclusion, exclusion, and withdrawal criteria. “Stopping rules" or "discontinuation criteria" for individual subjects, parts of trial, and entire trial are defined in this step. Rules are also set for accountability procedures for the drug and the placebo and comparator, if any.
A VBS study must exploit the “adaptive design” principles to develop the drug faster while achieving both efficiency and effectiveness. An adaptive design allows a company to change protocols at any stage during the clinical trial execution. This type of flexible design is essential to effectively respond to changes in the competitive and market dynamics.