Guidelines for Developing a Data and Safety Monitoring Plan: Appendix B

Sample of an Initial DSM Plan for a Medication Trial

The purpose of this Phase II clinical trial is to test the efficacy of aspirin versus placebo for treatment of cocaine dependence, using a randomized, double blind, and placebo-controlled design. The sample will be 80 healthy volunteers between 18 and 60 years of age who sign the consent form, are randomized and take the first dose of study medication. The sample will be recruited and treated at a local Addictions Clinic for 8 weeks. Study participants will be asked to come to the clinic three times per week. At each clinic visit study participants will fill out questionnaires, be asked about adverse events, provide a urine sample for toxicology analysis, and be medicated by the study nurse. No take home medications will be provided. Participants will be asked to come back to the clinic for follow-up at 3, 6 and 12 months after taking the last dose of study medication.

The Principal Investigator will be responsible of monitoring the safety and efficacy of this trial, executing the DSM plan, and comply with the reporting requirements. The PI will provide a summary of the DSM report to NIDA on an annual basis as part of the progress report. The DSM report will include the participants’ sociodemographic characteristics, expected versus actual recruitment rates, treatment retention rates, any quality assurance or regulatory issues that occurred during the past year, summary of AEs and SAEs, and any actions or changes with respect to the protocol. The DSM report to NIDA will also include, if applicable, the results of any efficacy data analysis conducted.

Data monitoring plan

Data will be collected using standardized paper forms and will only be identified with the study’s ID of the participant. The codes that link the name of the participant and the study ID will be kept confidential by the Principal Investigator in a secured cabinet. Collected forms will be securely transported to the PI’s data entry center. Data will be entered in the computer independently by two teams of trained data entry staff, and discrepancies corrected by a supervisor based on source documents. The study’s statistician will analyze the data, using the Clindat® software.

The primary outcome will be the percent of study participants in each group with 6 or more consecutive urine samples negative for cocaine. Secondary outcome measures include self-reported drug use and psychosocial functioning. Outcome data will be analyzed using chi-square, ANOVA, and HLM. The alpha level will be set at 5%.

Data quality will be monitored by random inspection of the completed forms by one of the research assistants and any problems detected will be discussed with the PI. If necessary, re-training of data collectors will be conducted.

Blind interim analysis of the data will be conducted when 50% of the sample is accrued. If the results show statistically overwhelming significant differences between groups, the blind will be broken and the study stopped.

Safety monitoring plan

During screening, study applicants will undergo a complete battery of medical laboratory tests and physical exam to determine their eligibility and safety of their participation in this study. Study applicants will be excluded if they have bleeding problems, peptic ulcer, or any other clinical problem that may contraindicate their participation in this study. During the treatment phase of the study, participants will be asked about adverse events at each clinic visit and vital signs will be obtained before administering the study medication. Patients will not receive the medication if they are bleeding or have any signs or symptoms that may contraindicate its administration.

All adverse events (AEs) occurring during the course of the study must be collected, documented, and reported to the Principal Investigator. The occurrence of AEs will be assessed at baseline and each clinic visit during the treatment phase of the study and again during the 6, 9 and 12-month follow-up visits. Each week a study investigator will review the AE Forms from the previous week for events that were reported as new or continuing. The study investigators will follow all AEs to the point of a satisfactory resolution. A study participant may have their medication discontinued of may be withdrawn from the study if the medically responsible investigator determines it is the best decision in order to protect the safety of a participant. All AEs will be assessed to determine if they meet criteria for an SAE.

Serious adverse events (SAEs), as defined by the FDA, will be systematically evaluated at each clinic visit. Any SAE, whether or not related to study medication, will be reported to the IRB, NIDA, and the FDA. The initial SAE report will be followed by submission of a completed SAE report to all three institutions.

In the event that a patient either withdraws from the study or the investigator decides to discontinue a patient due to SAE, the patient will have appropriate follow-up medical monitoring. Monitoring will continue until the problem requiring hospitalization has resolved or stabilized with no further change expected, is clearly unrelated to study medication, or results in death. Outcome of SAEs will be periodically reported to NIDA. A summary of the SAEs that occurred during the previous year will be included in the annual progress report to NIDA.