Identifying Aims, Objectives, Hypotheses, and Variables for a Clinical Study
The aims or goals of a study are short general statements (often just one statement) of the overall purpose of the trial. For example, the aim of a study may be “to assess the safety and efficacy of drug XYZ in patients with moderate hyperlipidemia.”
The objectives are much more specific than the aims. Objectives usually refer to the effect of the product on specific safety and efficacy variables, at specific points in time, in specific groups of subjects. An efficacy study may have many individual efficacy objectives, as well as one or two safety objectives; a safety study may or may not have efficacy objectives.
You should identify one or two primary objectives — those that are most directly related to the aim of the study and determine whether the product passes or fails in the study. You may then identify up to several dozen secondary objectives, which may involve different variables or the same variables at different time points or in different subsets of the study population.
You may also list a set of exploratory objectives, which are less important, but still interesting. Finally, you list one or more safety objectives (if this is an efficacy study) or some efficacy objectives (if this is a safety study).
A typical set of primary, secondary, exploratory, and safety objectives (this example shows one of each type) for an efficacy study might look like this:
Primary efficacy objective: To compare the effect of drug XYZ, relative to placebo, on changes in serum total cholesterol from baseline to week 12, in patients with moderate hyperlipidemia.
Secondary efficacy objective: To compare the effect of drug XYZ, relative to placebo, on changes in serum total cholesterol and serum triglycerides from baseline to weeks 4 and 8, in patients with moderate hyperlipidemia.
Exploratory efficacy objective: To compare the effect of drug XYZ, relative to placebo, on changes in serum lipids from baseline to weeks 4, 8, and 12, in male and female subsets of patients with moderate hyperlipidemia.
Safety objective: To evaluate the safety of drug XYZ, relative to placebo, in terms of the occurrence of adverse events, changes from baseline in vital signs (blood pressure and heart rate), and safety laboratory results (chemistry, hematology, and so on), in patients with moderate hyperlipidemia.
Hypotheses usually correspond to the objectives but are worded in a way that directly relates to the statistical testing to be performed. So the preceding primary objective may correspond to the following hypothesis: “The mean 12-week reduction in total cholesterol will be greater in the XYZ group than in the placebo group.”
Alternatively, the hypothesis may be expressed in a more formal mathematical notation and as a null and alternate pair:
Identifying the variables to collect in your study should be straightforward after you’ve enumerated all the objectives. Generally, you should plan on collecting some or all of the following kinds of data:
Basic demographic information (such as date of birth, gender, race, and ethnicity)
Information about the subject’s participation in the study (for instance, date of enrollment, whether the subject met each inclusion and exclusion criterion, date of each visit, measures of compliance, and final status (complete, withdrew, lost to follow-up, and so on)
Basic baseline measurements (height, weight, vital signs, safety laboratory tests, and so forth)
Subject and family medical history, including diseases, hospitalizations, smoking and other substance use, and current and past medications
Laboratory and other testing (ECGs, X-rays, and so forth) results related to the study’s objectives
Responses from questionnaires and other subjective assessments
Occurrence of adverse events
Some of this information needs to be recorded only once (like birthdate, gender, and family history); other information (such as vital signs, dosing, and test results) may be acquired at scheduled or unscheduled visits, and some may be recorded only at unpredictable times, if at all (like adverse events).
For very simple studies, you may be able to record all your data on a single (albeit large) sheet of ruled paper, with a row for each subject and a column for each variable. But in formal clinical studies, you need to design a Case Report Form (CRF). A CRF is often a booklet or binder with one page for the one-time data and a set of identical pages for each kind of recurring data.
Many excellent CRF templates can be downloaded from the web (or just enter “CRF templates” in your browser).