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| title | chunk | source | category | tags | date_saved | instance |
|---|---|---|---|---|---|---|
| Adaptive design (medicine) | 1/4 | https://en.wikipedia.org/wiki/Adaptive_design_(medicine) | reference | science, encyclopedia | 2026-05-05T09:48:46.125163+00:00 | kb-cron |
In an adaptive design of a clinical trial, the parameters and conduct of the trial for a candidate drug or vaccine may be changed based on an interim analysis. Adaptive design typically involves advanced statistics to interpret a clinical trial endpoint. This is in contrast to traditional single-arm (i.e. non-randomized) clinical trials or randomized clinical trials (RCTs) that are static in their protocol and do not modify any parameters until the trial is completed. The adaptation process takes place at certain points in the trial, prescribed in the trial protocol. Importantly, this trial protocol is set before the trial begins with the adaptation schedule and processes specified. Adaptions may include modifications to: dosage, sample size, drug undergoing trial, patient selection criteria and/or "cocktail" mix. The PANDA (A Practical Adaptive & Novel Designs and Analysis toolkit) provides not only a summary of different adaptive designs, but also comprehensive information on adaptive design planning, conduct, analysis and reporting.
== Purpose == The aim of an adaptive trial is to more quickly identify drugs or devices that have a therapeutic effect, and to zero in on patient populations for whom the drug is appropriate. When conducted efficiently, adaptive trials have the potential to find new treatments while minimizing the number of patients exposed to the risks of clinical trials. Specifically, adaptive trials can efficiently discover new treatments by reducing the number of patients enrolled in treatment groups that show minimal efficacy or higher adverse-event rates. Adaptive trials can adjust almost any part of its design, based on pre-set rules and statistical design, such as sample size, adding new groups, dropping less effective groups and changing the probability of being randomized to a particular group, for example.
== History == In 2004, a Strategic Path Initiative was introduced by the United States Food and Drug Administration (FDA) to modify the way drugs travel from lab to market. This initiative aimed at dealing with the high attrition levels observed in the clinical phase. It also attempted to offer flexibility to investigators to find the optimal clinical benefit without affecting the study's validity. Adaptive clinical trials initially came under this regime. The FDA issued draft guidance on adaptive trial design in 2010. In 2012, the President's Council of Advisors on Science and Technology (PCAST) recommended that the FDA "run pilot projects to explore adaptive approval mechanisms to generate evidence across the lifecycle of a drug from the pre-market through the post-market phase." While not specifically related to clinical trials, the council also recommended that they "make full use of accelerated approval for all drugs meeting the statutory standard of addressing an unmet need for a serious or life-threatening disease, and demonstrating an impact on a clinical endpoint other than survival or irreversible morbidity, or on a surrogate endpoint, likely to predict clinical benefit." By 2019, the FDA updated their 2010 recommendations and issued "Adaptive Design Clinical Trials for Drugs and Biologics Guidance". In October of 2021, the FDA Center for Veterinary Medicine issued the Guidance Document "Adaptive and Other Innovative Designs for Effectiveness Studies of New Animal Drugs".
== Characteristics == Traditionally, clinical trials are conducted in three steps:
The trial is designed. The trial is conducted as prescribed by the design. Once the data are ready, they are analysed according to a pre-specified analysis plan.
== Types ==
=== Overview === Any trial design that can change its design, during active enrollment, could be considered an adaptive clinical trial. There are a number of different types, and real life trials may combine elements from these different trial types: In some cases, trials have become an ongoing process that regularly adds and drops therapies and patient groups as more information is gained.
=== Dose finding design === Phase I of clinical research focuses on selecting a particular dose of a drug to carry forward into future trials. Historically, such trials have had a "rules-based" (or "algorithm-based") design, such as the 3+3 design. However, these "A+B" rules-based designs are not appropriate for phase I studies and are inferior to adaptive, model-based designs. An example of a superior design is the continual reassessment method (CRM).