Table 1: Summary of main Phase I clinical trial designs.

DesignsAdvantagesDisadvantages

Standard 3 + 3 designRobust.
Simple.
Easy to carry out.
MTD is not a dose with any particular probability of DLT, but in the range from 20% to 25% DLT.
Can not estimate MTD with target probability of DLT <20% or >33%.
Not all toxicity data of all patients are used to determine the MTD.
Many patients are likely to be treated at low doses.

ID isotonic designOnly assumes a monotonically increasing relationship between dose and toxicity.
Semiparametric.
Can estimate MTD with different TTL (0~100%).
Robust and easy to use.
Good for combination of multiple drugs and treatments.
The accuracy of MTD may not be as good as CRM or EWOC.
The trial efficiency may not be as good as CRM or EWOC.

CRM continual reassessment methodFit parametric model for dose toxicity relationship.
Adaptive optimal design.
Accurate estimation of MTD.
Improved trial efficiency.
Allow flexible MTD with different TTL.
High risk of patients being treated with over toxic dosages.
If the parametric model is not reliable, the result could be questionable.
May fail to find MTD.

EWOC escalation with overdose controlIncludes all advantages of CRM.
Controls the overdosing probability.
Further improves MTD accuracy and trial efficiency.
If the parametric model is not reliable, the result could be questionable.
May fail to find MTD.