Clinical Research Pilot Study Request for Proposals
RELEASE DATE:
Deadline for brief study outline:
Email researchgrants@alsa-national.org for study outline form.
The ALS Association’s (ALSA) is dedicating a major new scientific research program TREAT ALS (Translational Research Advancing Therapy for ALS) to focus specifically on drug discovery and the development of therapies that will effectively treat amyotrophic lateral sclerosis (ALS). Currently there is only one FDA approved drug for ALS, Riluzole, which has a modest effect on patient survival. There is a real need for the development of effective drugs for the disease. As part of this initiative TREAT ALS aims to focus efforts to accelerate clinical testing of compounds with promise for the disease. ALSA has partnered with the National Institute for Neurological Disorders and Stroke (NINDS) and sought community input to identify the most promising therapeutic candidates currently available that may be effective for the treatment of ALS. One by-product of this collaboration is a list of selected compounds described in a manuscript submitted for consideration to the journal Brain (refer to appendix 1 of this release).
This request for proposals (RFP) seeks to fund pilot clinical studies to obtain preliminary clinical data which will support applications to the National Institutes of Neurological Disorders and Stroke (NINDS) for subsequent larger clinical trials of an intervention to treat or prevent ALS. Although study designs are not limited to those including the prioritized compounds outlined in Appendix 1, applications considering studies of any one or more of these compounds to provide supporting data for larger clinical trials and of high scientific merit will be very favorably considered. Study designs of compounds not in Appendix 1 of high scientific merit and rationale will receive equally favorable consideration.
The proposed study must address questions that, when answered, will optimize the design of more definitive clinical trials rather than simply address the clinical question with lower power. The research proposal should directly address how the preliminary study will advance the design of a subsequent definitive clinical trial for efficacy.
Examples of relevant clinical research for this mechanism include, but are not limited to, the following:
- Studies to optimize the intervention strategy (e.g., dose, duration and frequency of dosing). For example, studies designed to investigate dose-concentration, dose-response, or concentration-response relationships may contribute to optimal dosage selection for definitive trials.
- Studies to assess the appropriate delivery system or parameter settings of an electronic device or surgical technique.
- Studies to assess the safety and tolerability at various doses or concentrations of a specific intervention or studies designed to select the best of two or more potential interventions or dosing regimens to evaluate in a subsequent definitive trial, based on tolerability or evidence of biological activity.
Note that in each of the above examples, the study is designed to provide specific data that will be essential to design the subsequent definitive efficacy trial. In many cases, a control group is not necessary nor preferable in order to achieve these objectives.
BUDGET: A maximum of $150,000/year for a maximum of 2 years
No indirect costs will be paid for these awards
APPLICATION RECEIPT DATES:
| Brief study outline | |
| Request by ALSA to submit full application | |
| Submission of full application | |
| Notification of award | |
| Funds begin on receipt of all relevant signatures | |
REVIEW CRITERIA
- Significance
- Approach
- Innovation
- Investigator
- Environment
- Appropriateness of Budget
(1) SIGNIFICANCE: Does this study address an important problem? Has the applicant addressed both the significance of the eventual definitive clinical trial AND the significance of this study in providing knowledge needed to proceed to the definitive clinical trial? Is there a sufficient body of high quality preclinical or clinical research that supports the rationale for the proposed study? What is the potential impact of the proposed intervention on health care and quality of life? If the aims of the study are achieved, how will these results contribute to the design and implementation of the definitive clinical trial?
(2) APPROACH: Are the conceptual framework, design, methods, and analyses adequately developed, well integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?
For the proposed preliminary study, reviewers will evaluate whether the approach is adequate in each of the following areas:
- The scientific soundness of the proposed methodology, such as translation of the clinical question into statistical hypotheses, selection of outcome measure(s), inclusion and exclusion criteria, plans for identifying, screening, and enrolling subjects, plans for randomization and masking, if appropriate, implementation of intervention (including determination of treatment dose), and plans for follow-up of patients;
- The soundness of plans for analysis of the primary and secondary questions, including the adequacy of the target sample size for achieving the goals of the study;
- The completeness and quality of the protocol and standardized procedures that will be used for this study;
- The ethical aspects of the study, including risks and benefits to patients, the adequacy of subject education and consent procedures, and safety protections;
- The adequacy of plans for safety monitoring of the study;
- The adequacy of data management and quality control procedures.
(3) INNOVATION: Are the aims of the study original? While the proposed study design, methods, and interventions may not necessarily be innovative, the underlying aims should represent an advancement in the field.
(4) INVESTIGATOR: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? The reviewers should consider training and expertise in the clinical problem and the proposed intervention, and training and expertise in clinical trials. If a multicenter study is proposed, the reviewers should also evaluate the investigator's ability to organize and manage the research group.
(5) ENVIRONMENT: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? Have appropriate agreements with participating industry sponsors, if any, been established?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items will be considered in the determination of scientific merit and the priority score:
BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research
Priority list for phase III ALS clinical trials.
A. Suitable for phase III trials in the near future
- Talampanel
- Tamoxifen
B. Already in phase III trials
- Ceftriaxone
- IGF-1 polypeptide
- Minocycline
- ONO- 2506
C. More data required prior to phase III testing
- AEOL 10150 (2, 3, 4)
- Arimoclomol (2, 3, 4)
- Celastrol
- Coenzyme Q10
- Copaxone (1, 4)
- IGF-1 viral delivery
- Memantine (1, 2, 3, 4)
- NAALADase inhibitors (1, 2, 3, 4)
- Nimesulide (1, 3, 4)
- Scriptaid (1, 2, 3, 4)
- Sodium Phenylbutyrate (2, 3, 4)
- Thalidomide
- Trehalose (1, 3, 4)
D. Already FDA approved as ALS therapy
- Riluzole
1 = transgenic efficacy animal studies 2 = human toxicology 3 = CNS pharmacokinetic studies 4 = Dose-ranging studies
