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Food and Drug Administration

Docket: 2004N-0181 - Critical Path Initiative Public Comments Submitted
July 30, 2004

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| | 1.  Hurdle Identification. Please describe the product           |  |
| |     development issue, the nature of the evaluation tool that is |  |
| |     out-of-date or absent, how this problem hinders product      |  |
| |     development, and how a solution would improve the product    |  |
| |     development process. Please be as specific as possible.      |  |
| |                                                                  |  |
| | > \# 1 Hurdle: There is no system set up for advocacy groups to  |  |
| | > interact with FDA and others on these issues.                  |  |
| | >                                                                |  |
| | > \# 2 Hurdle: The clinical trials system needs big improvement. |  |
| | > There is no national system for clinical trials that is fully  |  |
| | > integrated and links all the trials, people, and results and   |  |
| | > science together, additionally there is no system for diseases |  |
| | > like pancreas cancer that is modified to fit the needs of the  |  |
| | > disease and the community. There is no national pancreas       |  |
| | > biospecimen system or patient reqistry system to accommodate   |  |
| | > research.                                                      |  |
| | >                                                                |  |
| | > \# 3 Hurdle: Clinical trials design and what it takes to get   |  |
| | > drugs and treatments approved is an obstacle. The current      |  |
| | > system of how we do clinical trials is too slow, it takes way  |  |
| | > too long to get drugs to be tested empirically. The clinical   |  |
| | > trials system and product development is currently a one size  |  |
| | > fits all system. This does not work for diseases like pancreas |  |
| | > cancer where the mortality rate is so high and so fast and the |  |
| | > overall patient community is small in patient numbers.         |  |
| | >                                                                |  |
| | > \# 4 Hurdle: The science is not being well managed and mapped. |  |
| | >                                                                |  |
| | > #5 Hurdle: System is not set up for emerging science i.e.      |  |
| | > molecular based treatments and tailored treatment based on a   |  |
| | > patient\'s genetic blueprint. Assays for diagnosis, choosing   |  |
| | > treatments, looking at response to treatment etc. do not exist |  |
| | > for pancreatic cancer. Imaging is another area that is in      |  |
| | > great need for diagnostics and treatment management.           |  |
| |                                                                  |  |
| | 2.  Please rank each hurdle identified in Question 1, above, in  |  |
| |     priority order according to which hurdles create the most    |  |
| |     severe product development problems. That is, which problems |  |
| |     present the greatest opportunity for improving product       |  |
| |     development processes? Our goal is to identify those aspects |  |
| |     of product development that would most benefit from new      |  |
| |     evaluation tools.                                            |  |
| |                                                                  |  |
| | These are all very important, however in order for some to       |  |
| | happen, others need to happen first. So they are more in order   |  |
| | of chronology than priority.                                     |  |
| |                                                                  |  |
| | \# 1 Hurdle: There is no system set up for advocacy groups to    |  |
| | interact for the purpose of action with FDA and others on these  |  |
| | issues.                                                          |  |
| |                                                                  |  |
| | \# 2 Hurdle: The clinical trials system needs big improvement.   |  |
| | There is no national system for clinical trials that is fully    |  |
| | integrated and links all the trials, people, and results and     |  |
| | science together, additionally there is no system for diseases   |  |
| | like pancreas cancer that is modified to fit the needs of the    |  |
| | disease and the community. There is no national pancreas         |  |
| | biospecimen system or patient registry system to accommodate     |  |
| | research.                                                        |  |
| |                                                                  |  |
| | \# 3 Hurdle: Clinical trials design and what it takes to get     |  |
| | drugs and treatments approved is an obstacle. The current system |  |
| | of how we do clinical trials is too slow, it takes way too long  |  |
| | to get drugs to be tested empirically. The clinical trials       |  |
| | system and product development is currently a one size fits all  |  |
| | system. This does not work for diseases like pancreas cancer     |  |
| | where the mortality rate is so high and so fast and the overall  |  |
| | patient community is small in patient numbers.                   |  |
| |                                                                  |  |
| | \# 4 Hurdle: The science is not being well managed and mapped.   |  |
| |                                                                  |  |
| | #5 Hurdle: System is not set up for emerging science i.e.        |  |
| | molecular based treatments and tailored treatment based on a     |  |
| | patient\'s genetic blueprint and assays for diagnosis, choosing  |  |
| | treatments, looking at response to treatment etc. do not exist   |  |
| | for pancreatic cancer.                                           |  |
| |                                                                  |  |
| | 3.  For each problem identified, please indicate the type of     |  |
| |     drug, biologic, or device to which the hurdle applies.       |  |
| |                                                                  |  |
| | Our answer: This applies to any and all drugs for pancreatic     |  |
| | cancer, imaging of pancreatic cancer for detection and diagnosis |  |
| | and monitoring of the effects of treatment. This includes        |  |
| | treatment and symptom management and overall management of the   |  |
| | disease. Prevention of pancreatic cancer is on the distant       |  |
| | horizon, but we need to first be able to diagnose it at the      |  |
| | earliest possible time to maximize the effects of treatment and  |  |
| | interventions.                                                   |  |
| |                                                                  |  |
| | 4.  For each problem identified, if a solution would facilitate  |  |
| |     the development of drugs, biologics, and/or devices for a    |  |
| |     particular disease or categories of disease, please indicate |  |
| |     which diseases would be affected?                            |  |
| |                                                                  |  |
| | > PANCREATIC CANCER and other cancers as well that are under     |  |
| | > researched and progress has been virtually non existent.       |  |
| |                                                                  |  |
| | 5.  Nature of the Solution. For each problem identified, please  |  |
| |     describe the evaluation tool that would solve the problem    |  |
| |     and the work necessary to create and implement the           |  |
| |     tool/solution. For example, would a solution come from       |  |
| |     scientific research to develop a new assay or validate a new |  |
| |     endpoint? If the solution involves biomedical research,      |  |
| |     please specify the necessary research project or program.    |  |
| |     Would a tool be developed through data mining or computer    |  |
| |     modeling? Would the right tool be a new FDA guidance or      |  |
| |     industry standard? If work on a solution is underway, what   |  |
| |     steps remain? Are there other innovative solutions that      |  |
| |     could be explored?                                           |  |
| |                                                                  |  |
| | > \# 1 Hurdle Solution:                                          |  |
| |                                                                  |  |
| | a.  Develop a working partnership with key advocacy groups and   |  |
| |     key stakeholders to develop a national plan. Bring together  |  |
| |     experts in pancreatic cancer and develop a national game     |  |
| |     plan to get develop novel and innovative ideas that can be   |  |
| |     validated, approved for use in patients.                     |  |
| |                                                                  |  |
| | b.  Plan that is flexible, not bureaucratic and cumbersome,      |  |
| |     allows collaborative and progressive actions to be taken.    |  |
| |     Don\'t get bogged down in politics and policy, but one that  |  |
| |     has the scientific freedom, ability to change regulations if |  |
| |     warranted, while protecting safety and rights of patients.   |  |
| |                                                                  |  |
| | c.  Identify barriers to drug development on disease by disease  |  |
| |     basis, cross map them to determine similarities and          |  |
| |     differences, then map the national strategy taking these     |  |
| |     elements into account.                                       |  |
| |                                                                  |  |
| | > \# 2 Hurdle Solution:                                          |  |
| |                                                                  |  |
| | a)  Create a network (can be virtual) and coordinated system     |  |
| |     that can translate biological insights into clinical use and |  |
| |     translate clinical observations into laboratory              |  |
| |     investigations.                                              |  |
| |                                                                  |  |
| | b)  Utilize information technology, to develop an appropriately  |  |
| |     integrated system that will serve as an infrastructure to    |  |
| |     build a national research system that includes clinical      |  |
| |     trials system.                                               |  |
| |                                                                  |  |
| | c)  Develop a coordinated system especially for cancers like     |  |
| |     pancreas cancer. The PanCAN Research MAP and PanCAN Clinical |  |
| |     Trials database will begin to create the information base we |  |
| |     need to get the job done.                                    |  |
| |                                                                  |  |
| | d)  Develop key infrastructure resources such as biospecimen     |  |
| |     network and patient registry that contains clinically        |  |
| |     annotated and relevant data.                                 |  |
| |                                                                  |  |
| | e)  Develop business plan and execute the plan with key          |  |
| |     stakeholders at the table.                                   |  |
| |                                                                  |  |
| | f)  Develop clinical trials model systems that are novel and not |  |
| |     duplicates or minor revisions of old systems that do not     |  |
| |     work for pancreas cancer.                                    |  |
| |                                                                  |  |
| | g)  Develop financial and academic career model for researchers  |  |
| |     and industry in under researched diseases.                   |  |
| |                                                                  |  |
| | h)  Develop everyday methods that enable and empower the patient |  |
| |     to be involved in either or both, specimen donation and      |  |
| |     clinical research including developing a national \"ATM\"    |  |
| |     type system for integrating clinically annotated data that   |  |
| |     will be coded to the patient specimen, to a national patient |  |
| |     registry system as well as to the patients own medical       |  |
| |     records.                                                     |  |
| |                                                                  |  |
| | i)  Develop a system that analyzes drug failure and work to      |  |
| |     improve the rate of failure in pancreatic cancer that is     |  |
| |     disproportionately high.                                     |  |
| |                                                                  |  |
| | > \# 3 Hurdle Solution: A system that is faster and more         |  |
| | > flexible in pancreatic cancer. Optimize novel clinical trials  |  |
| | > specific to pancreatic cancer, do multi drug and combination   |  |
| | > trials in more of a \"plug and play\" type mindset.            |  |
| |                                                                  |  |
| | a)  ways to get patients into clinical trials sooner and more    |  |
| |     patients onto trials                                         |  |
| |                                                                  |  |
| | b)  ways for the advocacy community to work with the research    |  |
| |     community and FDA and NCI                                    |  |
| |                                                                  |  |
| | c)  develop the appropriate standardized technology and          |  |
| |     platforms for standardized protocols for specimen handling   |  |
| |     and acquisition.                                             |  |
| |                                                                  |  |
| | d)  integrate other disciplines that are essential to the        |  |
| |     process but may not be involved in oncology, such as         |  |
| |     gastroenterologists, general surgeons, primary care          |  |
| |     physicians, basic scientists, epidemiologists etc.           |  |
| |                                                                  |  |
| | e)  explore alternative trial designs to address specific        |  |
| |     problems in pancreatic cancer for example: the difficulty of |  |
| |     assessing response or benefit in patients with locally       |  |
| |     advanced and metastatic pancreatic cancer and the activity   |  |
| |     of new therapeutic strategies that may not kill tumor cells, |  |
| |     but stop their growth.                                       |  |
| |                                                                  |  |
| | f)  validate novel surrogate endpoints, including disease        |  |
| |     stabilization, biochemical markers, and results of           |  |
| |     functioning imaging studies.                                 |  |
| |                                                                  |  |
| | g)  design studies to include correlative components and design  |  |
| |     studies to maximize and leverage the amount of scientific    |  |
| |     data that is captured.                                       |  |
| |                                                                  |  |
| | h)  develop system for better sharing of data, mining and        |  |
| |     statistical, and mathematical models.                        |  |
| |                                                                  |  |
| | i)  develop standardized tiered consent form                     |  |
| |                                                                  |  |
| | j)  Use scientific tools to select patients for trials and       |  |
| |     treatments based on algorithm that optimizes potential       |  |
| |     utility of treatment.                                        |  |
| |                                                                  |  |
| | > \# 4 Hurdle Solution:                                          |  |
| | >                                                                |  |
| | > a\) Create mechanisms that get key stakeholders working well   |  |
| | > together.                                                      |  |
| | >                                                                |  |
| | > b\) Using the PanCAN-NCI Pancreatic Cancer Research MAP, and   |  |
| | > PanCAN\'s proprietary clinical trials database, work together  |  |
| | > in understanding the clinical trials landscape and the state   |  |
| | > of the science in pancreas cancer.                             |  |
| | >                                                                |  |
| | > c\) Work closely with FDA, NCI and their clinical trials       |  |
| | > experts along with the experts in pancreatic cancer clinical   |  |
| | > trials. There should be a national plan for clinical trials    |  |
| | > development that is cross coordinated within the public and    |  |
| | > private sectors.                                               |  |
| | >                                                                |  |
| | > d\) Facilitate the discovery and development of targeted       |  |
| | > therapeutics by using a national plan based on the PanC        |  |
| | > Research MAP.                                                  |  |
| | >                                                                |  |
| | > e\) Communicate the science, the opportunity and the results   |  |
| | > to the patient community and this can be accomplished through  |  |
| | > working partnerships with the pancreatic cancer advocacy       |  |
| | > community.                                                     |  |
| | >                                                                |  |
| | > f\) Develop mechanisms to ensure that research results and     |  |
| | > treatment advances are integrated out into community settings. |  |
| | >                                                                |  |
| | > #5 Hurdle Solution:                                            |  |
| | >                                                                |  |
| | > a\) Provide incentives to industry and equipment manufacturers |  |
| | > to work with the research community in understudied diseases   |  |
| | > and diseases with high mortality rates that have little to no  |  |
| | > measurable progress in the last ten years.                     |  |
| | >                                                                |  |
| | > b\) Facilitate interactions and collaborations between Key     |  |
| | > Advocacy groups , FDA, Industry, and NCI programs such as the  |  |
| | > Specialized Programs of Research Excellence (SPORES), Early    |  |
| | > Detection Research Network (EDRN) and the Mouse Models of      |  |
| | > Human Cancer Consortium (MMHCC), the Pancreatic Cancer Genetic |  |
| | > Consortium (PacGene) and the Pancreatic Cancer Collaborative   |  |
| | > Registry (PCCR).                                               |  |
| | >                                                                |  |
| | > c\) Identify the problem areas and the opportunities for       |  |
| | > scientific advancement.                                        |  |
| | >                                                                |  |
| | > d\) Develop simple, reliable, and valid instruments for        |  |
| | > assessing clinical benefit in pancreatic cancer patients.      |  |
| | >                                                                |  |
| | > e\) Develop an open source national pancreas cancer            |  |
| | > biospecimen repository system and patient registry as          |  |
| | > described in the National Biospecimen Network Blueprint.       |  |
| | >                                                                |  |
| | > f\) Develop everyday methods that enable and empower the       |  |
| | > patient community to be involved in either or both, specimen   |  |
| | > donation and clinical research this includes developing a      |  |
| | > national \'ATM\' type system for integrating the clinically    |  |
| | > annotated data that will be coded to the patient specimen, to  |  |
| | > a national patient registry as well as to the patients own     |  |
| | > medical records.                                               |  |
| | >                                                                |  |
| | > 6\. For each solution identified, please indicate which could  |  |
| | > be accomplished quickly, in less than 24 months, and which     |  |
| | > require a long-term approach?                                  |  |
| | >                                                                |  |
| | > If you bring together the right people with the right mindset  |  |
| | > and the right attitude. Every one of these solutions could be  |  |
| | > integrated into a pilot program that could be up and running   |  |
| | > within 24-36 months and validated within five years. This      |  |
| | > would require adequate resources and the will of many, but it  |  |
| | > is possible. In order to accomplish this, it needs to be a     |  |
| | > committee infrastructure and process that is not totally       |  |
| | > managed and run by any government agency.                      |  |
| | >                                                                |  |
| | > We can accomplish this by developing a pilot program that      |  |
| | > brings in business expertise from the private sectors,         |  |
| | > advocacy sectors, information techology sectors and other key  |  |
| | > private sector groups that have experience in designing        |  |
| | > nationally integrated systems. The government agencies while   |  |
| | > key stakeholders, their most important role is to bridge and   |  |
| | > link together innovative science with policy.                  |  |
| | >                                                                |  |
| | > \# 1 Hurdle: There is no system set up for advocacy groups to  |  |
| | > interact for the purpose of action with FDA and others on      |  |
| | > these issues.                                                  |  |
| | >                                                                |  |
| | > Time Frame for Solution: This could be up and running within   |  |
| | > 12 months.                                                     |  |
| | >                                                                |  |
| | > \# 2 Hurdle: The clinical trials system needs big improvement. |  |
| | > There is no national system for clinical trials that is fully  |  |
| | > integrated and links all the trials, people, and results and   |  |
| | > science together, additionally there is no system for diseases |  |
| | > like pancreas cancer that is modified to fit the needs of the  |  |
| | > disease and the community. There is no national pancreas       |  |
| | > cancer biospecimen system or patient registry system to        |  |
| | > accommodate research. The amount of support for the            |  |
| | > infrastructure and running of publicly funded clinical trials  |  |
| | > is inadequate.                                                 |  |
| | >                                                                |  |
| | > Time Frame for Solution: This can be accomplished in 24        |  |
| | > months. With key milestones in place at earlier intervals.     |  |
| | > Pilot could be up and running within 24 months.                |  |
| | >                                                                |  |
| | > \# 3 Hurdle: Clinical trials design and what it takes to get   |  |
| | > drugs and treatments approved is an obstacle. The current      |  |
| | > system of how we do clinical trials is too slow it takes way   |  |
| | > too long to get drugs to be tested empirically. The clinical   |  |
| | > trials system and product development is currently a one size  |  |
| | > fits all system. This does not work for diseases like pancreas |  |
| | > cancer where the mortality rate is so high and so fast and the |  |
| | > overall patient community is small in patient numbers.         |  |
| | >                                                                |  |
| | > Time frame for solution: A pilot system can be developed       |  |
| | > within 24 months if developed in conjunction with previous     |  |
| | > steps required for a national system.                          |  |
| | >                                                                |  |
| | > \# 4 Hurdle: The science is not being well managed and mapped. |  |
| | >                                                                |  |
| | > Time frame for Solution: Can be executed in the concurrent     |  |
| | > 24-36 months along with the previous recommendations.          |  |
| | >                                                                |  |
| | > #5 Hurdle: System is not set up for emerging science i.e.      |  |
| | > molecular based treatments and tailored treatment based on a   |  |
| | > patient\'s genetic blueprint. Assays for diagnosis, choosing   |  |
| | > treatments, looking at response to treatment etc. do not exist |  |
| | > for pancreatic cancer. Imaging is another area that is in      |  |
| | > great need for diagnostics and treatment management.           |  |
| | >                                                                |  |
| | > Time frame for Solution: This would be integrated into a pilot |  |
| | > program and could be up and running in 24-36 months.           |  |
| | >                                                                |  |
| | > 7\. For each problem identified, what role should FDA play and |  |
| | > what role shouldbe played by others? Should FDA play a         |  |
| | > convening role, bringing the relevant parties together to      |  |
| | > discuss an approach or solution? If so, who else should        |  |
| | > participate? Should FDA coordinate scientific research, the    |  |
| | > results of which would be publicly available? We are seeking   |  |
| | > input on ways to target FDA scientific and collaborative       |  |
| | > activities to help industry bring more safe and effective      |  |
| | > medical products to us for review.                             |  |
| | >                                                                |  |
| | > Most of our perspective is addressed in previous solutions to  |  |
| | > the hurdles. The government agencies such as FDA are key       |  |
| | > stakeholders, and their most important role is to bridge and   |  |
| | > link together innovative science with policy. To help address  |  |
| | > the barriers whether they are real or perceived and then work  |  |
| | > with the community to address each barrier through             |  |
| | > re-engineering and re-tooling of the system. The Critical Path |  |
| | > Initiative is a very good first step. FDA\'s role is to be     |  |
| | > part of the solution and to be a team player. FDA can assist   |  |
| | > in facilitating collaborations. FDA can help meld science and  |  |
| | > innovative thinking as it relates to policy modifications that |  |
| | > might be required to pilot innovative solutions to age- old    |  |
| | > problems. FDA can take the lead and demonstrate the capability |  |
| | > and expertise of the FDA in drug development for cancers like  |  |
| | > pancreatic cancer that have suffered from a tremendous lack of |  |
| | > progress. FDA can bring all of us together so we can           |  |
| | > collectively figure out a way for organizations to work        |  |
| | > together in a bureaucratic situation. FDA\'s role is to be     |  |
| | > dynamically responsive in working with the community to        |  |
| | > develop the most effective and efficient way to safely         |  |
| | > expedite innovative drugs and treatments to patients.          |  |
| |                                                                  |  |
| | 8\. What factors should guide FDA in setting priorities among    |  |
| | the hurdles and solutions identified?                            |  |
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| | Cancers that have little or no treatment options available       |  |
| | should be given the highest of priorities. One key factor needs  |  |
| | to be a complete and thorough examination of public and private  |  |
| | efforts aimed at disease specific cancer research and the        |  |
| | research progress for each area. MAP out all approved treatments |  |
| | including compendia listings. Drug development is a disease      |  |
| | specific endeavor and needs to be reviewed on that basis. Cross  |  |
| | map the progress with the state of the science to determine      |  |
| | scientific areas for opportunity that take advantage of          |  |
| | technology. Upon completion of that exercise, the FDA needs to   |  |
| | look at mortality of cancers and which cancers have not enjoyed  |  |
| | any progress in treatment, diagnosis and management. There       |  |
| | should be a high priority given to the needs of cancers like     |  |
| | pancreatic cancer, the 4th leading cause of cancer death and one |  |
| | which the patient community suffers from a severe lack of        |  |
| | treatment options. In cancers with many treatment options, FDA   |  |
| | should review areas of need and gaps in managing those types of  |  |
| | diseases and then facilitate collaborations aimed at national    |  |
| | strategies for those cancers.                                    |  |
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> Thank you very much for the opportunity to offer comment. We have
> attempted to scratch the surface on some very important issues for the
> entire community and look forward to engaging with you on more
> substantive and progressive interactions. The newly created Office for
> Oncology Products will hopefully help us all move in the direction
> needed.
>
> We are ready when you are to get started, we have an entire patient
> community of pancreatic cancer patients and families that is counting
> on all of us.
>
> Respectfully,
>
> Paula Kim
>
> President of Scientific and Government Affairs,
>
> Co-founder