This program provides assistance in dose level assignment for Accelerated
Titration Designs for Phase I Clinical Trials [Simon, Freidlin, Rubinstein, Arbuck,
Collins, Christian, Journal of National Cancer Institute, 1997; 89, 1138-47].
this program provides only general guidance related to the proposed
It is not meant to substitute for professional medical judgement in the treatment of
Microsoft Excel 5.0 or higher.
Each row corresponds to one patient. It contains a patient ID field and a section for each
treatment course. The program supports up to ten courses per patient. Each course section
consists of four columns: the date the course begins, the administered dose level, the
recommended dose level, and the worst toxicity. The worst toxicity is defined
to be the severity of the worst toxicity in any organ system, judged to be definitely or
probably drug related, and observed for the treatment course in that patient.
A separate Excel workbook file must be used for each phase I trial. Files for different
phase I trials must be saved under different file names, to avoid overwriting previously
accumulated data. The main spreadsheet in each workbook must be initially devoid of data
from any other trial or test.
To begin using the program, enter a protocol identifier (up to 8 characters) and a
design (2A, 2B, 4A or 4B). When a new patient has consented to treatment, a dose level
recommendation is obtained by clicking on an "Assign dose level" button. The
program will request a patient identifier. A patient identifier may be any label up to 8
characters.The program will then provide the recommended dose level, according to the
design used, for the first course of the new patient. The program automatically records
the recommended dose level in the appropriate column for the new patient. At that point
user may save the updated spreadsheet and exit.
Between runs of the spreadsheet macro, user should update the fields giving start dates
of the treatment courses, dose levels actually administered, and worst toxicities for all
previously entered patients. The program checks that: (a) all patients courses for
which recommended dose level has been assigned have been updated with start dates and
administered dose levels; and (b) that all courses starting more than 30 days before the
current date contain worst toxicity evaluation.
The program will also recommend dose levels for subsequent courses of previously
entered patients. After clicking on the "Assign dose level" button when prompted
for patient identification, provide the ID of a previously entered patient.
The program works based on dose level, not dose. The Accelerated Titration Designs call
for defining the dose levels based on approximately 40% increments.
It is important that the information entered into the worst toxicity fields be based on
careful assessment and complete observation of the at-risk period (at least 15 days). The
observation of the dose limiting toxicity, however, should be recorded as soon as it is
observed even if at-risk period has not been completed. No lower grades of toxicity should
be recorded, however, until the full at risk period has been completed. If a patient is
not evaluated for toxicity because of death (not drug related) or inaccessibility, the
worst toxicity should be recorded as NA (not available). Toxicities should be recorded
using one of the following short codes: LT, DLT, MOD, MILD, NONE or NA. Either upper or
lower case characters may be entered, but will be converted to upper case.