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needs to be included in the report will vary from study to study and from one drug
class to another and the applicant must decide, if possible after consultation with the
regulatory authority, what to include in appendix to the study report. The study
report should indicate what material is included as an appendix, what is in the more
extensive archival case report tabulations, if required by the regulatory authority, and
what is available on request.
For a controlled study in which critical efficacy measurements or assessments (e.g.,
blood or urine cultures, pulmonary function tests, angina frequency, or global
evaluations) are repeated at intervals, the data listings accompanying the report
should include, for each patient, a patient identifier, all measured or observed values
of critical measurements, including baseline measurements, with notation of the time
during the study (e.g., days on therapy and time of day, if relevant) when the
measurements were made, the drug/dose at the time (if useful, given as mg/kg), any
measurements of compliance, and any concomitant medications at the time of, or
close to the time of, measurement or assessment. If, aside from repeated assessments,
the study included some overall responder vs non-responder evaluation(s),
(bacteriologic cure or failure), it should also be included. In addition to critical
measurements, the tabulation should note whether the patient was included in the
efficacy evaluation (and which evaluation, if more than one), provide patient
compliance information, if collected, and a reference to the location of the case
report form, if included. Critical baseline information such as age, sex, weight,
disease being treated (if more than one in study), and disease stage or severity, is also
helpful. The baseline values for critical measurements would ordinarily be included
as zero time values for each efficacy measurement.
The tabulation described should usually be included in appendix 16.2.6 of the study
report, rather than in the more extensive case report tabulations required by some
regulatory authorities, because it represents the basic efficacy data supporting
summary tables. Such a thorough tabulation can be unwieldy for review purposes,
however, and it is expected that more targeted displays will be developed as well.
For example, if there are many measurements reported, tabulations of the most
critical measurements for each patient (e.g., the blood pressure value at certain visits
might be more important than others) will be useful in providing an overview of each
individual's results in a study, with each patient's response summarised on a single
line or small number of lines.
11.4.4
Drug dose, drug concentration, and relationships to response
When the dose in each patient can vary, the actual doses received by patients should
be shown and individual patient's doses should be tabulated. Although studies not
designed as dose-response studies may have limited ability to contribute dose-
response information, the available data should be examined for whatever
information they can yield. In examining the dose response, it may be helpful to
calculate dose as mg/kg body weight or mg/m
²
body surface.
Drug concentration information, if available, should also be tabulated (Appendix
16.2.5), analysed in pharmacokinetic terms and, if possible, related to response.
Further guidance on the design and analysis of studies exploring dose-response or
concentration response can be found in the ICH Guideline "Dose-Response
Information to Support Drug Registration".