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

Sample of an Initial DSM plan for a Non-Medication Behavioral Treatment Clinical Trial

The purpose of this Stage II clinical trial is to test the efficacy of cognitive behavioral therapy versus cognitive behavioral therapy plus voucher incentives for treatment of cocaine dependent individuals with major depression. The study will use urn-randomized design, stratifying by age and gender. The sample will be 280 healthy volunteers between 18 and 60 years of age, who meet the study’s inclusion criteria, sign the consent form, and receive at least one session of therapy. The sample will be recruited and treated at a local Addictions Clinic for 8 weeks by Masters degree counselors. Study participants will not be provided any medication for treatment of cocaine dependence or major depression. Participants will be asked to come to the clinic three times per week to fill out questionnaires, be asked about their feelings, drug use, and any Adverse Events (AEs) or Serious Adverse Events (SAEs), provide a urine sample for toxicology analysis, and meet with a counselor for 1 hour to receive the respective therapy. Participants will be asked to come back to the clinic for follow-up at 3, 6 and 12 months after attending the last session of therapy.

The Principal Investigator will be responsible for monitoring the safety and efficacy of this trial, executing the Data and Safety Monitoring (DSM) plan, and complying 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, when available, 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 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 will be corrected by a supervisor, based on source documents. The quality of the data will be monitored once per month. 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, index of depression, 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. Therapists will receive standardized training on each of the therapies. Adherence to therapy techniques will be monitored using videotapes and individual supervision. If therapy drift is observed the therapists will be re-trained.

Blind interim analyses of the data will be conducted at two points when 50 and 75% of the sample has been 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 psychological tests to determine their eligibility and safety of their participation in this study. Special attention will be placed on history of suicidal ideation or suicide attempts. Suicidal risk factors, including suicidal ideation, intent, and plan will be assessed at each study visit. Patients who are at risk to commit suicide will not receive the study therapies and will be evaluated to determine whether continued study treatments are appropriate, and will be offered access to additional treatment including medication, if warranted. Study participants who have high or persistent risk of suicide or require anti-depressant medication will be discontinued from the study and will be offered mental health treatment in this clinic.

In this study we will use the FDA definition of serious adverse events (SAEs). SAEs will be systematically assessed at each clinic visit. Any SAE, whether or not related to study intervention, will be reported to the IRB and NIDA. The initial SAE report will be followed by submission of a completed SAE report to both 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 be monitored by the investigator via ongoing status assessment until 1) a resolution is reached i.e., the problem requiring hospitalization has resolved or stabilized with no further changes expected 2) the SAE is determined to be clearly unrelated to the study intervention, or 3) the SAE 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.