Research: Before we can even start

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ResearchBefore we can even start!

• Neil R. M. Buist MD
• Professor Emeritus, Pediatrics and
  Medical Genetics
• Oregon Health Science University
  Portland OR
• Sept 07

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The Halcyon Days

• We screened for diseases that we had no idea of
  the biological variability, the need for Rx or
  even the prognosis eg PKU!
• We made the medical Foods MSUD formulas in the
  Laboratory
• We invented new analytical methods for new
  diseases
• If we thought we had a good idea, we just went
  ahead and did it!
• We even used high doses of strychnine for NKH!

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This paperless society!Preparing

• Research grant?
• 100-1000 pages, 3-12 months
• Regulatory paperwork
• 500-5000 pages, 100 forms 1
  year
• IRB
• 50-500 pages 25 forms
  Months
• Continuing surveillance and reporting
• 10-1000 pages, must keep until pt is
  adult

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Regulatory paperwork for 10 person study
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Regulatory paperwork for BH4 Study ONE patient!
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Regulatory paperwork for ONE patient!
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Visit 1A forms binder!
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One patient s regulatory paperwork for 6 visits
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Pre-study IRB forms - 1

• Proposed project Questionnaire
• Initial Submission Checklist   
• Initial Review Questionnaire
• Complete Grant Proposal
• Lay Language Protocol Summary
• Data Safety Plan Questionnaire
• Individual Investigator Agreement
• Application for individual investigator to be
  covered off campus
• Use of Ionizing Radiation in Human Subject
  Research

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Pre-study IRB forms - Consents

• Adult, Child, Media Genetic consents also in
  other languages?
• HIPAA Research Authorization
• HIPAA for Existing PI
• HIPAA Waiver of Agreement
• HIPAA Data Use Agreement
• HIPAA Business Associate Agreement
• Other HIPAA Forms

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Pre-study IRB forms Drug Studies

• All Company package inserts safety sheets etc
• Pyrogenicity, Purity Potency Testing nfo
• All advertisements for subjects ads, Craigs
  List, TV etc
• Survey data collection forms
• Collaborative agreements
• CLIA certification for each lab
• Clinical billing schedule, Fee agreements
  industry budget
• Use of ionizing radiation form
• Humanitarian device exemption application
• IND IDE
• FDA forms regarding exemptions
• Interinstitution agreements

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Other IRB Forms

• Project Revision/Amendment Form
• Adverse Experience Report Form
• Adverse Experience Flow Chart
• Tissue Use Review Form
• Project Termination Form
• Protocol Deviation Form

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IRB Forms Summary

• Animal studies 15
• Conflict of Interest 2
• Human research subjects 14
• HIPAA 7
• DNA/Infectious agents 6
• OHSU Agreements 3
• Sponsored research 16
• Technology research transfer 8

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• CHANGE OF TOPIC
• FROM IRBs
• TO
• PROBLEMS WITH MEDICAL FOODs

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Medical Foods for Inborn Errors of Metabolism

• Definition
•   foods (specially) formulated to be consumed or
  administered enterally under the supervision of a
  physician and are intended for the specific
  dietary management of a disease or condition for
  which distinctive nutritional requirements based
  on recognized scientific principles are
  established by medical evaluation.
• Orphan Drug Amendments of 1988 (section 5 (b)(3)
  of the Orphan Drug Act 21 USC 360ee (b)(3))

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Medical foods are in a never-never land

• Food is consumers responsibility with no
  reimbursement except WIC, Food Stamps etc
• Drugs are typically covered by insurance via
  state legislative mandates
• Medical Foods are in limbo considered neither
  food nor drug each state has adopted some sort
  of insurance mandate for them
• Some only cover PKU
• Some only cover till age 18 or 21
• Some have unrealistic financial limits
  1,500-4,000
• Some limit the choices of food
• Only 14 states have no limits for any disorder at
  any age
• State mandates are not portable between states

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Problems with Medical nutritional therapy

• Two main types Protein sources
  
• ( infant formulas, pills, powders etc)
  
  Energy sources
  
  (pasta, baking mixes, cookies, soups, etc)
• It is impossible to give a balanced diet without
  using both kinds
• Very limited choices (90 v. 10,000 regular
  foods)
• Costly (3-20 times more than regular foods)
• Cost for 12 year old with PKU 12,000/year

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Daily food requirement for 9 y old with PKU

• TARGET NUMBERS
• Calories Protein g
• Medical Foods Regular Foods
• Normal 1900 0
  40
• PKU 1900 35
  5
• You can use a diet based mainly on, high protein
  infant formula/pills products to provide 1500
  Cals 80g protein
• Annual cost 12,600
• OR
• Less hi-pro products and lots of variety from
  hi-cal/lo-pro products to provide 1500 Cals 35g
  protein
• Annual cost 8,100

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Insurance Coverage for Screening and Medical
Foods

• Newborn Screening is done in all states 4-35
  tests
• S1858 would require Extended NBS in all states
• S1858 has no provision to provide treatment
• Treatment by Medical Foods is required by all
  states
• BUT
• There is no consistency, some states only include
  PKU
• Others have unrealistically low financial caps
• Others exclude certain types of Food that are
  critical
• There is no guarantee of portability
• Federal programs ERISA, Tricare preempt state
  laws
• and do not ensure coverage

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What needs to be done?

• We have been to 12 Senate /House offices this
  week to present the case for a bill that
• a) establishes a standard of continuity of
  treatment for IEMs to meet both national and
  internationally accepted standards for treatment,
  and
• b) addresses the specific issue regarding
  nationwide and equitable insurance coverage for
  the treatment of IEM.
• This provision could be incorporated this into
  the NBS legislation that is expected to be
  reviewed by the Senate HELP Committee in October.
  
• Families, affected by the current situation
  should approach their own legislators and
  present their own stories with a request for
  action. (We can help with info).

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Bonbouche!

• Let food be your medicine and
• medicine be your food
• Hippocrates 400 BC