Confirmatory Clinical Trial (CCT)

A Confirmatory Clinical Trial (CCT) is a Clinical Trial that is performed in a late-stage phase to evaluate and prove the efficacy or safety of a medical treatment or a device.

• AKA: Confirmatory Randomized Clinical Trial (CRCT).
• Context:
  • It usually comes after an early-phase clinical trials (e.g. exploratory clinical trial).
• Example(s):
  • Therapeutic Confirmatory Clinical Trial to Evaluate the Safety and Efficacy of Treatment of Articular Cartilage Lesions With CartiLife.
  • …
• Counter-Example(s):
  • Adaptive Clinical Trial,
  • Explanatory Clinical Trial,
  • Exploratory Clinical Trial,
  • Pragmatic Clinical Trial.
• See: First-In-Human (FIH) Clinical Trial, Decentralized Clinical Trial, Correlation, Therapy, Outcomes Research, Health System, Causality, Confounding, Drug Clinical Trial, Medical Device Clinical Trial, Clinical Procedure Trial, Observational Clinical Trial, Interventional Clinical Trial, Clinical Trial Management System, Clinical Trial Monitoring System, Clinical Trial Protocol, Clinical Trial Design System, Clinical Endpoint.

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References

2021a

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Confirmatory_trial Retrieved:2021-11-14.
  • A confirmatory trial is an adequately controlled trial where hypotheses are stated in advance and evaluated according to a protocol. This type of trial may be implemented when it is necessary to provide additional or firm evidence of efficacy or safety.

    The mechanism of the trial implements a key hypothesis of interest which is rigorously tested at the end of the confirmatory trial and directly follows the predefined primary objective of the trial. Of importance in a confirmatory trial is the process of estimating with due precision potential effects attributable to the treatment, the quantity of effects and relating these effects to their clinical significance.

    According to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use: "Confirmatory Trials are intended to provide firm evidence in support of claims and hence adherence to protocols and standard operating procedures is particularly important; unavoidable changes should be explained and documented, and their effect examined."

    Basic outline of the process of a confirmatory trial

    1. A design justification and statistical aspects such as the principal features of the planned analysis, is established as part of the initial protocol.
    2. The confirmatory trial should be concise in addressing only a specific number of questions.
    3. The confirmatory trial should clarify key clinical questions relevant to efficacy and/or safety clearly and definitively.
    4. The target patient population segmented for the trial is clearly outlined, understood and defined as this may influence the test sites and scientists (practitioners, specialists, etc.) involved.

2021b

• (NCI, 2021) &rArr: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/confirmatory-clinical-trial In: NCI's Dictionary of Cancer Terms, Retrieved: 2021-11-14.
  • QUOTE: A study that confirms how well a new treatment works after it was shown in early-phase clinical trials that it might be beneficial for patients. New drugs that are given an accelerated approval by the U.S. Food and Drug Administration (FDA) to treat a serious or life-threatening disease, such as cancer, are required to be tested in a confirmatory clinical trial. This is done to verify that they really work when they are tested on many more people in a randomized study. The FDA may remove a drug from the market if a confirmatory clinical trial shows that the drug is not beneficial for patients.

2019

• (EMA/CHMP, 2019) ⇒ Committee for Medicinal Products for Human Use (2019). "Guideline on the investigation of subgroups in confirmatory clinical trials". EMA/CHMP/539146/2013.
  • QUOTE: Confirmatory clinical trials are performed in late-stage drug development to inform a risk-benefit decision and to justify a treatment recommendation. For confirmatory trials, usually robust evidence for therapeutic efficacy is required in a relatively broad patient population that is representative of patient population (...)

1998

• (ICH, 1998) ⇒ ICH Expert Working Group (1998). "ICH Harmonised Tripartite Guideline Statistical Principles For Clinical Trials E9". In: International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use.
  • QUOTE: A confirmatory trial is an adequately controlled trial in which the hypotheses are stated in advance and evaluated. As a rule, confirmatory trials are necessary to provide firm evidence of efficacy or safety. In such trials the key hypothesis of interest follows directly from the trial’s primary objective, is always pre-defined, and is the hypothesis that is subsequently tested when the trial is complete. In a confirmatory trial it is equally important to estimate with due precision the size of the effects attributable to the treatment of interest and to relate these effects to their clinical significance.

2007

• (EMA/CHMP, 2007) ⇒ Committee for Medicinal Products for Human Use (2019). "Reflection Paper On Methodological Issues In Confirmatory Clinical Trials Planned With An Adaptive Design".
  • QUOTE: Confirmatory trial, confirmatory nature of a trial: In section 2.1.2 in ICH-E9 a confirmatory trial is defined as "an adequately controlled trial in which the hypotheses are stated in advance and evaluated. As a rule, confirmatory trials are necessary to provide firm evidence of efficacy and safety".

1996

• (Parmar et al., 1996) ⇒ Mahesh K. B. Parmar, Richard S. Ungerleider, and Richard Simon (1996). "Assessing Whether to Perform a Confirmatory Randomized Clinical Trial". In: Journal of the National Cancer Institute (JNCI), Volume 88, Issue 22.
  • QUOTE: A confirmatory randomized clinical trial is a trial that is aimed at assessing whether a treatment effect observed in a previous randomized trial (or trials) is real and important.

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