One important issue is the apparent low success rate of drug discovery grant applications at the NIH over the past several years, both real (in terms of the actual numbers of drug discovery applications that are funded) as well as perceived (in terms of the types and ranges of comments commonly seen in the pink sheets).

From having participated regularly in a drug discovery special emphasis panel at the CSR, I wonder if there might be some structural issues surrounding the new drug discovery initiatives at NIH, and would like to ask Drs. Buckholtz and Refolo to comment on some of the following considerations:

1) Drug discovery study section members come in with quite varied backgrounds and perspectives, with some strongly favoring pharma-style, assay-based discovery (e.g., high-throughput screening of chemical compound libraries), others favoring hypothesis-driven testing in animal models, and others still mostly favoring the optimization of drug molecules whose targets have already been validated in the clinic. As a result, it seems difficult to achieve the level of...  Read more

One important issue is the apparent low success rate of drug discovery grant applications at the NIH over the past several years, both real (in terms of the actual numbers of drug discovery applications that are funded) as well as perceived (in terms of the types and ranges of comments commonly seen in the pink sheets).

From having participated regularly in a drug discovery special emphasis panel at the CSR, I wonder if there might be some structural issues surrounding the new drug discovery initiatives at NIH, and would like to ask Drs. Buckholtz and Refolo to comment on some of the following considerations:

1) Drug discovery study section members come in with quite varied backgrounds and perspectives, with some strongly favoring pharma-style, assay-based discovery (e.g., high-throughput screening of chemical compound libraries), others favoring hypothesis-driven testing in animal models, and others still mostly favoring the optimization of drug molecules whose targets have already been validated in the clinic. As a result, it seems difficult to achieve the level of consensus necessary for a numerical score that is competitive against those emerging from traditional study sections of long-standing which typically have very tight scientific and experimental focus.

2) Exacerbating this issue is that drug discovery applications for any and all neurological or psychiatric diseases seem to come to the same study section. Thus, the disease focus of the grant application becomes a significant element (that can be plus or minus) of the grant score, in effect, pitting different diseases against each other for perceived importance. Again, this is in contrast to conventional study sections in which the focus of the study section is a given.

3) Most study section members still have a strong predilection—both conscious and subconscious—for traditionally structured, hypothesis-driven applications, yet "discovery science" by its very nature must play by different rules at least part of the time. This builds in a natural bias towards late-stage drug development studies (such as second/third generation drug and drug delivery optimization studies), at the expense of the very early-stage, high-risk, high-gain drug discovery proposals. In pharma this would effectively shut off the front end of the drug development pipeline.

4) Finally, there appears to be significant uncertainty among study section members as to what role the NIH should play in the drug discovery process—should a "drug discovery" study section at the NIH favor only proposals to develop new drug molecules specifically for the clinic, or should it also favor more basic science grants that develop research tools that help to build the scientific foundations upon which discovery science is based?

Of course, none of these issues would probably be all that significant if funding levels were much, much higher! But as only one or a few grants, in these times, have any likelihood of receiving funding in any given study section cycle, all such issues that contribute breadth and diversity to drug discovery study sections (which would seem at first to be a good thing), also make it difficult to achieve enough consensus to translate even significant enthusiasm in a study section for a given proposal into a fundable score.

As a result, I must admit that my drug discovery colleagues and I have become increasingly less likely to submit true drug discovery grant applications to the NIH, rather relying on foundation support for drug discovery efforts until the science matures enough to be cast into a traditional NIH grant application—one not directed through the drug discovery mechanisms!

View all comments by Donald C. Lo

I am responding to the comments of Dr. Lo. Since 1998, we at the Alzheimer's Drug Discovery Foundation (ADDF) and the Institute for the Study of Aging (ISOA) have provided more than $27 million for early-stage drug discovery grants for AD and related dementias, for exactly the reasons Dr. Lo describes. Many of our grants go to the type of programs Dr. Lo is referring to, namely, early-stage programs that may not be fundable by NIH study sections and require foundation funding. We also are co-sponsors of the NIH NIA R21 program for "drug discovery in AD." Investigators who have received foundation grants from us have obtained preliminary data, and gone on to obtain NIH funding. We are actively seeking applicants for our AD drug discovery grant programs. We encourage all interested investigators (including those in private biotech companies) to apply to ADDF, including those who intend to apply, or are applying to NIH for drug discovery in AD and related to dementias. For NIH applicants, we can accept the NIH grant format without...  Read more

I am responding to the comments of Dr. Lo. Since 1998, we at the Alzheimer's Drug Discovery Foundation (ADDF) and the Institute for the Study of Aging (ISOA) have provided more than $27 million for early-stage drug discovery grants for AD and related dementias, for exactly the reasons Dr. Lo describes. Many of our grants go to the type of programs Dr. Lo is referring to, namely, early-stage programs that may not be fundable by NIH study sections and require foundation funding. We also are co-sponsors of the NIH NIA R21 program for "drug discovery in AD." Investigators who have received foundation grants from us have obtained preliminary data, and gone on to obtain NIH funding. We are actively seeking applicants for our AD drug discovery grant programs. We encourage all interested investigators (including those in private biotech companies) to apply to ADDF, including those who intend to apply, or are applying to NIH for drug discovery in AD and related to dementias. For NIH applicants, we can accept the NIH grant format without further changes, reducing paper work. For programs not intended for NIH, the scientific component of the application is only five pages. We have no deadlines. If there are any questions regarding process, or inquiries about possible funding, we are happy to discuss potential programs with applicants. Please email me at hfillit@alzdiscovery.org, or call either myself or Antony Horton, PhD, our Director of Scientific Affairs at 212.935.2402. Howard Fillit, MD Executive Director Alzheimer's Drug Discovery Foundation

References:
www.alzdiscovery.org

View all comments by Howard Fillit