Microsoft Excel Dose Level Assignment Program
for Accelerated Titration Designs for Phase I Clinical Trials

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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].

Warning:
this program provides only general guidance related to the proposed designs.
It is not meant to substitute for professional medical judgement in the treatment of individual patients.

Software requirements:
Microsoft Excel 5.0 or higher.

Spreadsheet Layout
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.

Operating instructions
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.