Treatment Trials and Drug Development: Overview
The largest program at SMRI is for the identification of medications that will improve the treatment of schizophrenia and bipolar disorder. Although medications have been available since the 1960s, they have proven to be only partially effective. Many individuals affected with these diseases continue to have symptoms even when taking available medications, while others find it difficult to take medications because of side effects.
I. Regular Treatment Trials
The purpose of this program is to support the testing of medications to assess their efficacy for treating schizophrenia and bipolar disorder. At any given time, SMRI is supporting 40-50 treatment trials, the majority of which are generic and/or off-label medications. SMRI expects to fund 5-10 additional trials this year. To view a list of SMRI-funded trials, click on List of Awarded Treatment Trials. To view a description of a trial, click on the "select" button to the left of the grant identification number. The list can be sorted numerically/alphabetically by clicking on a column head.
What drugs can be tested? SMRI is most interested in supporting research on the efficacy of drugs for which pharmaceutical companies are unlikely to be interested because the drugs lack commercial potential. Such drugs include those which have lost patent protection, off-label indications, repurposing, etc. SMRI aims to support clinical trials testing the efficacy of compounds or biological interventions. Although studies can include a psychosocial component, studies that have a psychosocial intervention as the primary focus will not be considered, nor will analyses of existing data, or trials of drugs focused on alleviating side effects of existing medications.
Who is eligible to apply?
Applications will be accepted from researchers in any country except where prohibited by United States law. The skills and academic experience of the applicant will be considered, but no particular academic degree is required.
How are applications submitted, and when is the deadline?
Applications must be submitted electronically on the SMRI website by 11:59 p.m. Eastern Standard Time on October 1 of each year.
What is the maximum award given?
For most awards the maximum amount $300,000 per year for up to three years, depending on the stage of development of compounds to be tested and the type of trial required. Special treatment trials (see below) may be funded at a higher level.
May I include indirect costs in my budget?
Yes, indirect costs of up to 15 percent may be included as part of the total grant budget, i.e., the total direct and indirect costs for each year cannot exceed $300,000.
What may I include in my budget?
You should request whatever funds you will need to conduct the proposed research. This may include money for salaries, supplies, laboratory costs, patient reimbursement, testing, etc. We are flexible on what applicants may include. We look at the budget vis a vis the proposed research, and we are especially impressed by economy.
How does the review process work?
Treatment trial grant applications are reviewed by at least three peer reviewers. A priority score is compiled from all reviewers, and the applications are ranked according to merit.
How abbreviated should my CV be?
CV's should be no more than five pages in length.
What do the members of the review committee really like?
We like economy. Ask for what you need and no more. No applicant has enhanced his or her standing by padding the budget. On the other hand, if you need the full amount, ask for it. We evaluate the budget simultaneously with the scientific content in what is essentially a cost-benefit analysis. You can attach one or two reprints to section 7 of the application if needed to explain a new technique or provide preliminary data, but for the majority of applications, they are not necessary. If we need more information, we will ask for it.
When will I find out if my application is funded?
Our complete application review cycle is approximately 4 to 6 weeks from deadline to notification.
If my application is selected for funding, when can I expect my funding to begin?
If your application is selected for funding, you will be required to complete and return a grant agreement along with two other accounting forms, a copy of IRB or Ethical Committee's approval letter, and a copy of the approved patient informed consent form for your grant project. Awards are tentatively scheduled for payment in February, pending receipt of the required documents.
Assistance for Applicants: 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 Controls: For treatment trials using placebo controls, applicants may wish to consider using the Sequential Parallel Comparison Design (SPCD) (see attachment). It was originally described by Fava et al. in Psychotherapy and Psychosomatics 72:115-27, 2003 and has been licensed to RCT Logic LLC under Matt Bowman. For therapies which do have therapeutic benefit, SPCD can, over a wide range of treatment responses, increase power for trials using placebo controls, regardless of whether placebo response is expected to be high or low. Applicants who wish to consider using SPCD should contact Mr. Bowman for additional details and include any costs involved in their budget.
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 (http://www.nimh.nih.gov/research-funding/grants/nimh-policy-on-data-and-safety-monitoring-in-extramural-investigator-initiated-clinical-trials.shtml) 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.
II. 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.
Whom should I contact if I have additional questions?
Ms. Jana Bowcut
Treatment Trials Administrator
The Stanley Medical Research Institute
8401 Connecticut Avenue, Suite 200
Chevy Chase, MD 20815
updated July 2012