Titecrm

1) Choose prior distribution for b parameter of logistic family

2) Assign first patient to dose level for which prior probability of DLT is closest to the desired percentile

3) Observe outcome and update posterior distribution

Assign next patient to dose level with probability of DLT closest to desired percentile; go to step 3) Sampling continues until fixed number N patients are treated

1) Choose prior distribution for b parameter of logistic family

2) Begin at lowest dose. Enroll 3 patients, observe outcomes and update posterior distribution

3) Determine dose level with probability of DLT closest to desired percentile, but escalate no more than one level; go to step 3)

Sampling continues until fixed number N patients are treated

1) Choose prior distribution for b parameter of logistic family

2) Choose T, duration of time over which toxicity will be monitored for each patient and tint, interval between dose cohorts (e.g., half-month)

3) Begin at lowest dose. Enroll 3 patients, follow for tint and observe outcomes

4) For all patients enrolled thus far, calculate g(x, u) (see text); then update posterior distribution

Determine dose level with probability of DLT closest to desired percentile, but escalate no more than one level; go to step 4) Sampling continues until fixed number N of patients are treated

More patients treated at therapeutic dose levels Utilizes all information available to choose next dose level

Targeted percentile is explicit

Less aggressive escalation than

CRM Utilizes all available information to choose next dose level Targeted percentile is explicit

Incorporates late toxicities Reduces trial duration Utilizes all information available to choose next dose level

Targeted percentile is explicit

Requires software to implement First patient could be assigned any dose and dose escalation can jump more than one level leading to higher observed toxicity rates

Requires software to implement

Requires software to implement More toxicities will be observed, particularly if they occur toward end of monitoring period T

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