Suggestions For Scientists Who Wish To Propose Interventions
The review committees also consider logistical constraints. For example, agents that must be administered by daily injection, or which must be stored cold with fresh materials provided daily, or which are very expensive to obtain, are not practical within the ITP protocols.
- The ITP Access Committee and Steering Committee evaluate each proposed intervention to evaluate the likelihood that the agent will have a beneficial effect on mouse health and lifespan, and to see if it will be practical to include the intervention in the ITP program. Criteria considered can include some of the following kinds of evidence:
- Data from pilot studies of lifespan (in rodents or invertebrates)
- Data from effects on specific diseases and processes thought to play a role in aging, from human studies or studies in model organisms.
- Data from cell cultures relevant to biochemical effects
- Epidemiological evidence for health benefits
- It is extremely helpful if proposals include data on bioavailability and toxicology in rodents, as well as proposals for evaluating some expected physiological or biochemical effect in rodents to assure that the intervention as used in the ITP has the expected biological effects. Such data, even from short-term studies, are very helpful in deciding whether a proposed dose is likely to tolerated and effective over a longer course of treatment. For any intervention for which the toxicity in mammals is unknown, a preliminary study in rodents to analyze toxicity, preferably including organ pathology, is highly valuable, because the ITP committees are reluctant to accept a proposal for an agent whose potential for rodent toxicity is entirely unknown.
- Proposals to study complex mixtures, such as plant extracts, pose a particular challenge, especially if the active ingredient(s) are unknown. The concern is that the extracts available may have different concentrations of the active ingredient(s), as well as variable levels of other contaminants with unknown beneficial or harmful effects. In addition, it is difficult to interpret studies of blood levels of a complex mixture whose active components are not known. Proposals to study complex mixtures would in nearly all cases benefit from clear documentation of physiological effects in rats or mice (or even humans) that could be used to assess the ability of the mixture, at the dose(s) proposed, to modify biochemical or physiological endpoints in mammals. Applications that lack mechanisms to validate the activity of the agent and demonstrate its efficacy in some physiological assays have not been competitive. It is incumbent upon applicants proposing to use complex mixtures to document efforts to standardize production of the mixture as well as efforts to identify active ingredients.
- Applicants are welcomed to propose multiple agents for test, or to propose a rationale for testing multiple doses of a single agent, or to propose combinations of agents with complementary activities. Three examples of successful ITP proposals (PDF, 1.15M) are provided. Prospective collaborators are also invited to discuss their ideas for ITP interventions by emailing Dr. Francesca Macchiarini at NIA or any of the three site directors: Dr. Richard Miller; Dr. David Harrison; Dr. Randy Strong.