MPS Society Survey Response from Sen. Judd Gregg

Senate Health Education Labor and Pensions Committee

Attn: Katy French, MS, Majority Staff Research Assistant

Re: Survey of NIH Issues

This letter has been drafted in response to the survey we received during our meeting on January 17th 2003. I have reviewed the survey regarding the experience the National MPS Society has had with National Institutes of Health, our answers are listed in the order the questions appear on the survey document.

The National MPS Society serves children and families struggling with MPS (Mucopolysaccharidosis) disorders. MPS disorders are multi systemic lysosomal storage disorders wherein the body lacks the ability to produce certain natural enzymes in sufficient quantities. The lack of enzyme production results in the storage of deposits in the bodies cells, as a resulting in cells that are progressively damaged. The damage occurs throughout the body and is profound in the heart, bones, joints, respiratory system and central nervous system. The disorders are degenerative and result in very complex management issues and in most cases death in childhood.

Our organizations experience with the NIH and research in general

As of FY2000, the NIH has historically funded approximately 85% of the research being conducted by the Scientific Advisory Board of the National MPS Society, a group of many of the nation’s most qualified investigators in MPS and lysosomal storage disorders. The remaining 15% comes from a number private sources including the National MPS Society and other non profit organizations. Public and privately funded research has grown steadily in recent years, a short time ago MPS was a relatively obscure field of study. The MPS related research proposals supported by the NIH have increased at a moderate rate, particularly since 1998.

NIH supported research has contributed greatly to the knowledge and understanding of MPS disorders and the underlying biology of these disorders. Currently, we have an ongoing dialog with the National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Diabetes Digestive and Kidney Disorders (NIDDK), National Institute of Child Health and Human Development (NICHD), the Office of Rare Diseases (ORD) and National Center for Research Resources (NCRR). We have also met with the Center for Scientific Review (CSR) regarding study section policy issues.

Meetings with NINDS, NIDDK, NICHD and ORD have, and continue to, consist of discussions of MPS research issues and how we may collaborate in advancing this field of study and research in pursuit of effective therapies. These institutes sponsored and supported a scientific conference focusing on the central nervous system in MPS disorders in September of 2002, the conference was jointly planned by the NIH, National MPS Society and members of the National MPS Society Scientific Advisory Board. NCRR continues to support a number of MPS and related disease animal models. We are currently discussing MPS research priorities and the areas most in need of advancement. Our goal is to make meaningful progress in developing therapeutic options for treating MPS disorders and determining how the NIH may affect positive action in this regard in 2003.

Public Input in the NIH Research Planning and Allocation Process

Representatives of the National MPS Society have served on an advisory committee for any NIH Institute or Center. Members of our Board of Directors and I have had contact with Office of Public Liaison (OPL) officers in NINDS, NIDDK and NIAMS. Our contacts with NIDDK and NIAMS OPL officers were brief and usually intended to gain access to appropriate institute officers when initial contact was made.

We have been in frequent contact with the OPL at NINDS and our contact has been positive in nature. Initially our contact with the NINDS OPL was to gain access to NINDS officers and information. As time has passed, the NINDS OPL has expressed interest in our organizations efforts and has solicited information and material from our organization on MPS disorders, disease management and organizational services.

The National MPS Society does not currently have a Memoranda of Understanding (MOU) with any NIH Institute or Center. MOU development has not been discussed in our meetings with NIH, therefore I cannot comment with respect to its implementation or impact. The Society has no previous experience with development or implementation of MOU’s however, as per the question posed, the Society would consider the participating in the development of an MOU. In our view its content would reflect the establishment of principal corporative goals related to the enhancement of investigator and Institute collaboration with respect to the study of the Blood Brain Barrier in Lysosomal Storage Disorders and mechanisms to implement research in pursuit of effective therapies. The larger impact and cross cutting nature of advancement in this field of study and usefulness of lysosomal storage disorders, particularly MPS as model disorder, would justify such action.

Concerning the question addressing the possibility of patient advocate training to serve on review panels (study sections) at NIH similar to other government agencies. While I strongly support healthy interaction between the NIH and disease groups, the review of investigator proposals must remain the domain of scientists fully qualified in the basic underlying biology of the disorders and diverse experience in the field of study in question. Easily accessed training and or informational resources to educate the public about the review process at NIH would be beneficial.

Internal and External Communication

Our organization as noted above does work with multiple institutes, I would describe the level of communication and coordination between the Institutes, Offices and Centers as adequate to excellent. The efficiency and effectiveness of communication and collaboration is often dependent on the performance of individual NIH officers, that is, with appropriate commitment both communication and collaboration takes place and is effective. From our organizations perspective the principal challenge may be development of consistent leadership within Institutes with respect to specific disorders and initiatives, given the strict controls, time constraints and work load NIH officers work under and what may be organizational challenges to implementing decisive action on critical research issues.

While we do not have specific structural recommendations with respect to improvement of multi Institute ? multi disciplinary research collaboration and communication, it would be logical to assume that employing additional program staff and resources would improve the ability of NIH Institutes to carry out these efforts.

We have not had any experience that would allow meaningful comment regarding coordination between the NIH and other HHS agencies.

With respect to the question regarding what barriers exist that make relationships with NIH and the private sector difficult. In my view one of the principal barriers to non profits working effectively with NIH is the lengths one must go to educate themselves how NIH works and what officers to approach, what resources are available to the consumer as well as the challenges involved in moving the scientific community to join the dialog with NIH officers and advocates.

It is noteworthy that the Office of Rare Diseases (ORD) has recently established a series of workshops titled “Gaining Access to Research Resources”. The purpose of these workshops is to inform the rare disease community about the internal workings of NIH and other federal agencies (FDA) that provide resources and services to the rare disease community. One member of our Board of Directors attended this workshop on January 11th 2002 and found it quite useful. We encourage the continuation of this and other programs to facilitate private sector/NIH communication and collaboration.

Allocation and Priority Setting

Regarding the impact of top leadership vacancies at NIH on allocation and priority setting, given our experience, it has not been evident to us that these vacancies have had a negative impact on the allocation of resources in MPS research, nor do we have specific suggestions with respect to Institute leader recruitment.

With respect to difficulty reporting allocations of dollars to disease specific areas, we understand that basic science is difficult to attribute to specific diseases, dollars spent in one diseases category are often double counted as expenditures in related diseases and that in light of the fact that Congress funds NIH on an Institute level and some variability exists between accounting practices. When we obtain funding information for MPS research from the NIH OBF, we are given the expenditures for “MPS related research” which covers a much broader field of study.

In my view however the NIH reports allocations as accurately as possible given these difficulties. With respect to specific recommendations, it would be logical to assume that in the long run, parody of accounting practices of Institutes and Centers could improve the situation.

With respect to the five criteria that NIH uses to make priority setting and allocation decisions, from an objective standpoint, we believe the criteria used represent a sound basis for which to make these critically important decisions and maintain the independence required to ensure NIH functions in an scientifically sound and equitable manner.

Grant Application Process *

With respect to the question pertaining to the NIH grant application process, it was noted that the mechanics of submitting applications to the NIH is reasonable, the volume of paperwork processed at the NIH must be extensive, the expanded use of technology to improve the efficiency of submissions and allow NIH to focus more on the substantive aspects of the process rather than paper shuffling is attractive. It was also noted that faster responses from study sections to allow resubmission of material without missing funding cycles would be beneficial.

Basic Verses Applied (Translational) Research*

With respect to the question how should NIH evaluate what is an appropriate balance between basic and applied (translational) research it was noted that a balance is needed between PhD basic reviewers and MD translational reviewers or the translational values particularly for disease focused research may be less appreciated. Additionally is was noted that NIH could support more translation from animal models to clinical trials as well as scaling up from rodent to large animal studies as pre clinical trials. Credit should be given to NINDS for its implementation of special grant mechanisms bridging preclinical and clinical trials as well as to NIDDK and NCRR for support of large animal models and “bridge money” that prevent valuable animal models from being lost.

Barriers to Developing and Implementing Translational Protocols *

Regarding barriers to developing and implementing translational protocols, it was noted that a major barrier may be insufficient interaction between clinical and basic researchers, the current reorganization of review bodies at NIH may present an opportunity to mix basic and clinically oriented researchers. In addition there is a clear consensus that the allocation of resources remains an issue, to quote one scientist “Researchers go where the money is, make funding available and those with the best ideas will go after it.” One recommendation put forth by an investigator and approved of by the National MPS Society to support translation to clinical trials, is for the NIH to establish a mechanism to support grants specifically for clinical development focused on rare diseases like the MPS disorders.

(*) Indicates that the answers to these questions were developed in consultation with the National MPS Society SAB.

Closing Comments

The National MPS Society supports the continued improvement of the NIH, however, we have found our contact and collaboration with the National Institutes of Health to be a positive and worthwhile endeavor.

The National MPS Society extends our appreciation to Senator Gregg and the Senate Health Education Labor and Pensions Committee for your interest in our views regarding the National Institutes of Health. We look forward to our continued communication with Congress on this and other matters of interest to the MPS and rare disease community.

Respectfully Submitted on 2-22-03 By

Les Sheaffer
Board of Directors, National MPS Society Inc.
Chairman, Committee on Federal Legislation