Concomitant medication data

An essential detail for the statistical programmer to watch for in prior or concomitant medications data is whether or not the start and stop dates are important for analyses. Unfortunately, it is often the case that the importance of the timing of prior or concomitant medications is not determined until after much of the data have been entered or even after the database is closed to entry. For instance, it may be decided later that a specific concomitant medication has to be watched carefully for interaction with a medication used in the study. If insufficient attention was placed on the quality of the medication start and stop dates, then determining whether there is overlap with study medication is difficult if not impossible. 

Like concomitant medication data, patient medical history data are collected in one of two forms a list-type free-text format where the histories get coded, or a pre-categorized data format. Here is the free-text CRF format ... 

INPUT SAMPLE CONCOMITANT MEDICATION DATA. data cm ... 

Here again PROC SQL is used where DATA steps may have been used before. In this single PROC SQL the treatment data are joined with the concomitant medications data and unique medications are selected within a patient. 

Please outline any concomitant medications that are permitted for the duration of the trial. If the medicinal product (s) is currently licensed it is recommended that the current summary of producf characteristics (Previously known as the data sheet) is consulted for information on potential drug interactions. 

Demographics and Trial-Specific Baseline Data 27 Concomitant or Prior Medication Data 27 Medical History Data 29 Investigational Therapy Drug Log 30 Laboratory Data 31 Adverse Event Data 32 Endpoint/Event Assessment Data 35 Clinical Endpoint Committee (CEC) Data 36 Study Termination Data 37 Treatment Randomization Data 38 Quality-of-Life Data 40... 

Imagine you have a data set of adverse event data and a data set of concomitant medications, and you want to know if a concomitant medication was given to a patient during the time of the adverse event. The following program defines the two data sets and joins them with PROC SQL so that you get all medications taken during any specific... 

The following example relies on more PROC SQL, a little DATA step programming, a few SAS macro variables, and a final PROC REPORT for table presentation. Here are the concomitant medication summary annotated SAS program, notes for the program, and the output. 

Additional objectives of clinical trials conducted in Phase II may include evaluation of potential study endpoints, therapeutic regimens (including concomitant medications) and target populations (e.g., mild versus severe disease) for further study in Phase II or III. These objectives may be served by exploratory analyses, examining subsets of data and by including multiple endpoints in trials. 

It is reasonable that data should be required to demonstrate whether the response of patients to a new active substance is likely to change or be changed by concomitant medication. However, there is clearly a huge number of potential drug combinations, and some rational selection is required. To assist with the selection of drug combinations for which data are required, the following seven questions at least should be asked. 

Individual subject/patient data including demographics, concomitant medication, blood/urine levels, laboratory tests, and adverse reactions... 

This critical section should include individual patient data in a tabulated form. Demographic values (age, sex, race, etc.), patient inclusion and exclusion criteria, relevant clinical measures for the particular study must also be included. Special clinical and laboratory measures used for the study must have a rationale for these tests as well as an explanation for the significance of the results. All concomitant medications used during the clinical trial must be listed for each patient admitted into the study. Other clinical observations of less relevance should be addressed. 

The protocol should list all medications that patients are allowed to receive simultaneously with the study drug. Any contraindicated medications or those that are to be excluded during the investigation because they might interfere or interact with the study drug also should be listed. It should be emphasized that patients who receive any kind of concomitant medication not permitted in the protocol will be dropped from the study, and their data will not qualify for inclusion in the final statistical analysis of efficacy. 

Based on published data in humans, concomitant medications were classified as potential inhibitors (cimetidine, fluoxetine, levopromazine, paroxetine, and thioridazine) or inducers of haloperidol metabolism (carbamazepine, phenobarbital, and phenytoin). 

All research personnel must search for clues about safety events from many sources, such as information in clinical records at the study sites information in data collection forms (e.g. CRFs, diary cards, quality-of-life forms, psychiatric rating scales, etc.), occurrence of missed and/or unscheduled visits, dropouts and withdrawals use of any concomitant medications/devices and abnormal laboratory data. AEs may also occur simply as a result of study procedures and study participation. Information about definitions of AEs and requirements for reporting AEs must be clearly stated in the protocol and explained to the site staff, who must also be educated in the correct procedure and immediate requirement for reporting any AE suspected to be serious or unexpected as per the regulatory definitions. 

---