The treatment trial application consists of 7 parts:
Part 1– Investigators. Please list the principal investigator and all co-investigators for the study. CVs are required for the PI and all co-PIs (not to exceed 5 pages). These CVs should be attached in the “attachments” section in Part 5.
Part 2- Treatment Trial Details. Fill in the details of the treatment trial, noting that sample size and sample design are required fields. Note that SMRI gives strong preference to randomized, double-blind studies.
Part 3- Abstract and Proposal. Contains fields to paste in the study abstract and proposal. Please note the character limits (which includes spaces). The proposal limit equates to about 5 pages. Figures and tables should be included in the “attachments” section in Part 5, and should be limited to 1-2 figures per application.
Part 4-Blood Brain Barrier. Please provide information on whether the compound crosses the blood brain barrier. There are no character limits for the associated text box.
Part 5- References and Attachments. Attach the list of references, not to exceed five pages. CVs and figures should be attached in the “attachments” section.
Part 6– Budget Items. Provide a list of budget items for the study. Salary costs should be listed individually for each person, but other items can be grouped by category. If more detail is needed, the review panel will ask for it.
Part 7– IRB approval status.
After completing all 7 parts, you will have the opportunity to review your application and print if desired. Please hit “submit application” to enter your application into the system for review. Please note that only the applications that have been “submitted” from your account will be reviewed.
Additional Application Information:
Again this year, SMRI is offering assistance for treatment trial applicants. Many applicants have good ideas regarding a drug to be studied but are unfamiliar with some of the complexities of carrying out such trials. Any applicants who wish to do so can indicate on their applications that, if approved for funding, they will ask SMRI consultants to help develop the details for any of the following:
- Optimal trial design
- Inclusion and exclusion criteria for patient selection
- Development of clinical report form (CRF)
- Data management, including the possibility of using SMRI for central data entry
- Evaluation of dropout data
- Statistical analysis
The two consultants SMRI is using in this regard are Drs. John Davis (University of Illinois at Chicago and SMRI Associate Director for Treatment Trials) and Mark Weiser (Chaim Sheba Medical Center, Tel Aviv), both experienced treatment trial experts. If an applicant wishes to use these consultants for any items on the above list, they should not include a cost for this in their budget and SMRI will add the estimated cost.
Placebo-Controlled Clinical Trials: Applicants may wish to consider the Sequential Parallel Comparison Design [SPCD] (Fava M et al, Psychotherapy and Psychosomatics 2003; 72: 115-27), which is a proven, highly effective, partial enrichment trial design and analysis method. SPCD enables efficient signal detection, while ensuring complete integrity, validity and superior generalizability. This design and analysis paradigm significantly reduces clinical trial risk, time and cost. Empiric evidence shows that it consistently lowers placebo response and variability, and offers improved power and predictivity at lower sample sizes, in comparison to parallel arm designs with or without placebo lead-in, in a wide range of therapeutic indications and interventions. SPCD has demonstrated reliable therapeutic signal detection, while meeting regulatory standards of integrity. This partial enrichment strategy is superior in generalizability and efficiency to single stage parallel arm and other two-stage alternatives. SPCD is exclusively licensed by PPD which offers tools for design, execution, and analysis that comprise the proprietary Trimentum™ technology. Applicants interested in learning more about the Trimentum design are welcome to contact PPD for further information, and review www.ppdi.com/Trimentum.**
Data Analysis and Access: For large trials we encourage building into your protocol an interim analysis. Since SMRI often supports more than one trial on a drug, we sometimes ask investigators to modify their protocol so that their data can be combined with other trials on the same drug.
Data from well-characterized clinical samples constitute an important scientific resource. SMRI believes that their full value can only be realized if they are made available, under appropriate terms and conditions, in a timely manner to the wider scientific community. SMRI expects and supports the timely release and sharing of final research data (raw, individual patient data) from SMRI-supported studies for use by other researchers, and we support the general guidelines developed by NIH in this regard. Limited access datasets from treatment trials supported by SMRI, will be made available for distribution no later than six months after the acceptance for publication of the main findings from the final data set.
SMRI recognizes that data sharing may be complicated or limited, in some cases, by organizational policies, local IRB rules, and local, State and Federal laws and regulations. The rights and privacy of individuals who participate in SMRI-sponsored research must be protected at all times. Thus, data intended for broader use should be free of identifiers that would permit linkages to individual research participants and variables that could lead to deductive disclosure of the identity of individual subjects. When data-sharing is limited, applicants should explain such limitations in their applications.
To assure that the confidentiality and privacy of study participants are protected, all investigators seeking access to data from SMRI-supported studies must execute and submit as their request a Data Use Certification (DUC). As a condition of receiving the limited access dataset, the requesting investigator must agree to the terms specified in the DUC.
SMRI Data and Safety Monitoring Board Policy
Since 2009, the Stanley Medical Research Institute has required that all newly funded studies involving more than minimal risk be overseen by a Data and Safety Monitoring Board (DSMB). DSMBs are currently required for most studies funded by the National Institutes of Health and the United States Food and Drug Administration. DSMBs are also being increasingly required for articles on clinical trials submitted to medical journals.
At this time, there is some variation in terms of how DSMBs are constituted and what their duties are. We would suggest that DSMBs overseeing SMRI-funded trials meet the following requirements:
- The DSMB should have a minimum of 3 members, at least one of whom is outside of the Institution performing the trial. It is strongly recommended that at least one member of the DSMB have proficiency in biostatistics or clinical trial design. It is also strongly recommended that at least one member of the DSMB be able to communicate in verbal and written English.
- The DSMB should meet at least once every 6 months. Meetings by teleconference are acceptable.
- The DSMB should prepare a written report at least once a year and at the end of the study. These reports should be submitted to SMRI along with the fourth quarter report.
- The DSMB should have access to all of the relevant data of the study, including the number and nature of serious adverse events in each treatment arm.
- Feel free to contact SMRI with any questions concerning the DSMB or with suggestions for DSMB members.
The most comprehensive reference on DSMBs can be found at:
Additional references include the following:
- Wittes J et al. Monitoring the randomized trials of the Women’s Health Initiative: the experience of the Data and Safety Monitoring Board. Clin Trials 2007;4:205–206.
- Witts J. Forming your phase III trial’s data and safety monitoring board: a perspective on safety.J Investig Med 2004;52:453–458.
- Lang T et al. Data safety and monitoring boards for African clinical trials. Trans R Soc Trop Med Hyg 2008;102:1189–1194.
- NIMH Collaborative HIV/STD Prevention Trial. Role of data safety and monitoring board in an international trial. AIDS 2007;21(suppl 2): S99–102.
- Czaja SJ et al. Data and safety monitoring in social behavioral intervention trials: the REACH II experience. Clin Trials 2006;3:107–118.
- Hedenmalm K et al. The conscientious judgement of a DSMB—statistical stopping rules re-examined. Eur J Clin Pharmacol 2008;64:69–72.
Special Treatment Trials and Drug Development
SMRI also supports special treatment trials and occasional drug development. Special treatment trials are usually multi-center trials that require more than $300,000 per year to carry out. Such trials are usually reserved for medications for which preliminary SMRI-supported trials have been promising.
SMRI has, in the past, also supported the development of promising medications at selected corporate biotechnology companies. At this time new applications are not being accepted.