What is it? Why is it important?

Before a therapeutic product, be it a Medicinal Product (MP) or a Medical Device (MD), is sold on the market, it must undergo several mandatory processes.

Mandatory processes differ depending on the type of product. The clinical development of:

  • MPs typically consists of 4 phases, with phase I / II / III and IV
  • MDs is less standardized. According to risk assessment, its development is divided into stages: pilot, pivotal and post-market stage

The clinical development MP-phases and MD-stages are described in further details under more.

More

Here a rough overview regarding the development of MPs and MDs.

MPs clinical development phases:

  • Pre-clinical studies: a new IMP is identified and tested in the laboratory on living cells and animal models
  • Phase I: first-in-human studies, with safety being the main concern. Which is the maximum tolerated dose?
  • Phase II studies: Established dose in Phase I is tested for safety and efficacy. The aim is to define the lowest required effective dose coupled with a minimum occurrence of Adverse Reactions (AR)
  • Phase III studies: The efficacy and safety of the drug is compared with a current standard treatment, or against a placebo
  • Phase IV studies: are done after the IMP has been approved and released on the market. The aim is to study how the now approved MP operates within the general population. Long term or still unknown (rare) safety data are collected. Other aspects such as quality of life, or cost effectiveness are also included

By providing scientific evidence from phase III studies that a MP is both effective and safe, allows manufacturers to apply for market authorization from regulatory authorities.

Quality needed to develop the drug must also be proven (e.g. GMP).

MDs clinical development stages:

  • *Pilot stage: these studies primarily collect information regarding IMD limitations and advantages. This will help to plan further required steps in IMD development
  • Pivotal stage: these are confirmatory studies that evaluate the clinical performance, effectiveness and safety of the IMD
  • Post-market stage include:
    • Additional confirmatory studies to establish MD clinical performance or effectiveness in a broader population
    • Observational studies for better understanding of safety

What do I need to do?

Familiarise yourself with the required processes for therapeutic product development. Be aware that the potential risk to your study participants differs depending on:

  • Its regulatory status. Does you study use a pre-market or post-market product?
  • The MP phase of your study (e.g. phase / - IV)
  • The MD stage of your study (e.g. pilot- post-market)

Before marked approval: the efficacy and safety of new therapeutic products are studied and followed-up in a few thousand carefully selected participants. Due to the small and highly selected population and the limited duration of these studies, only common side effects are identified at this stage.

After market approval:a much larger and heterogeneous population is exposed. More side effects will be observed and reported by patients and healthcare professionals, including those that occur only sporadically, and those with long-term outcome.

More

MPs clinical development and potential risks to study participants:

  • Phase I: Carries the highest safety risk (especially first-in-human studies). Small test groups (>20) with healthy volunteers or patients with the disease under investigation
  • Phase II: Test groups enrolling patients with the disease remain small. Many safety risks are still unknown. Consequently, risks to participants remain high
  • Phase III: Large test groups based on multi-centre international studies. Safety risks are better defined and the risk for participants is lower
  • Phase IV: Safest type of study. Evaluation focuses on long term and rare safety risks

MDs clinical development stages and potential risks to study participants:

  • Pilot stage: Includes first in human and feasibility studies. Carries the highest safety risk (especially first-in-human studies)
  • *Pivotal: Large numbers of subjects can be recruited, sample size is statistically driven
  • Post-market stage: Safest type of study. Evaluation may focus on long term and rare safety risks

In order to protect participants from unnecessary risks, the risk-benefit ratio is continuously reassessed. Actions are taken if new information indicates that the therapeutic product is no longer as safe and effective as previously thought (e.g. implementation of risk reduction measures).

Where can I get help?

Your local CTU can support you with experienced staff regarding this topic

References

ISO 14155:2020 Medical Device (access liable to cost) – see in particular annex

  • Annex I Clinical development stages
Abbreviations
  • AR – Adverse Reactions
  • CTU – Clinical Trials Unit
  • GMP – Good Manufacturing Practices
  • IMD – Investigational Medical Device
  • ISO – International Organization for Standardization
  • MD – Medical Device
  • MP – Medicinal Product
  • IMP – Investigational Medicinal Product
Basic ↦ Safety ↦ Safety Data ↦ Product Development
Study
Basic

Provides some background knowledge and basic definitions

Basic Protocol
Basic Statistics
Basic Monitoring
Basic Drug or Device
Basic Biobanking
Concept

Starts with a study idea

Ends after having assessed and evaluated study feasibility

Concept Protocol
Concept Statistics
Concept Drug or Device
Concept Biobanking
Development

Starts with confidence that the study is feasible

Ends after having received ethics and regulatory approval

Development Protocol
Development Statistics
Development Drug or Device
Development Biobanking
Set-Up

Starts with ethics and regulatory approval

Ends after successful study initiation

Set-Up Protocol
Set-Up Ethics and Laws
Set-Up Statistics
Set-Up Drug or Device
Set-Up Biobanking
Conduct

Starts with participant recruitment

Ends after the last participant has completed the last study visit

Conduct Protocol
Conduct Statistics
Conduct Drug or Device
Conduct Biobanking
Completion

Starts with last study visit completed

Ends after study publication and archiving

Completion Protocol
Completion Statistics
Completion Drug or Device
Completion Biobanking
Current Path (click to copy): Basic ↦ Safety ↦ Safety Data ↦ Product Development

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