1. Human Research Protections in 2008: The View from 30,000 ft. Daniel Nelson Outgoing Member, SACHRP Co-Chair, Subpart A Subcommittee Presentation to the Secretary’s Advisory Committee on Human Research Protections (SACHRP) July 16, 2008

2. How many angels can dance on the head of a pin? With apologies to Thomas Aquinas

3. This should not be what we’re all about!

4. Put another way… We spend too much time drowning in the details, and not enough time at 30,000 ft... or at least above sea level

5. Patchwork Quilt of Regulations…or… The Common Rule is Not Truly Common FDA Federally Funded (OHRP) Voluntary Application of Common Rule Unregulated Research HIPAA

6. “When you’ve seen one IRB… you’ve seen one IRB” IRBs are especially prone to “the one right way to do things” There may often be more than one right way, but that doesn’t mean they all need to be practiced… simultaneously, interchangeably, contradictorily We should minimize variability where possible, without sacrificing flexibility Consent form templates, common application forms, definitional interpretations

7. Alternative Models for an Evolving Research Environment (I) Research enterprise (esp. clinical research environment) has evolved considerably since 1970s Oversight system has failed to evolve to keep pace with volume, complexity and nature of research it oversees Research approaches increasingly do not fit neatly into current/traditional models of oversight Biobanking Population-wide studies Internet research International collaborations Multicenter trials

8. Alternative Models for an Evolving Research Environment (II) “Single site systems in a multi-center world” Predicated on local review of single sites Multi-center protocol is effectively a take-it-or- leave-it proposition for individual sites No effective means to modify underlying issues But… 300 versions of the “perfect consent form” Ineffective oversight of study-wide issues by patchwork quilt of independent sites AE reporting  example of positive reform

9. Mission Creep Combination of factors Uncertainty in applying definition(s) of Human Subjects Research Well-intended overreaching If a little protection is good, shouldn’t a lot of protection be better? After all, the IRB has an important job, with a lot riding on it! What is the harm in erring on the side of reviewing things that might technically fall outside those (admittedly blurry) lines? No one else to do it  give it to the IRB IRBs don’t do well with review/oversight of activities that are not Human Subjects Research

10. Ripe for Mission Creep? Athletics Administration Maintenance Garbage Clinical Care Education QI Human Subjects In Vitro Animal Subjects Case Reports Research Finance Policy Surveys Clinical Trials Observational

11. What requires IRB review? Where should the lines be drawn, in separating “Human Subjects Research” from activities that do not require IRB review… Quality improvement? Case reports? Classroom projects? De-identified specimens or data? Public health surveillance or interventions? Innovative clinical care? Key informant interviews about programmatic or organizational issues? Training or center grants? Other?

12. Why do we assume the worst? A system (or at least interpretations and practices) based on worst case scenarios e.g., investigators with wrongful intent, going to considerable lengths to re-identify genetic sequences they have agreed to use in a de-identified manner, by cross-linking to reference specimens that do not exist One sure way to eliminate risk  NO RESEARCH If we accept that research is a societal good, we accept that, by definition, some risk is acceptable… but are we obligated or justified in assuming the worst, in the absence of evidence that the worst is occurring… or is any more than a hypothetical?

13. “The national system for the protection of human research participants is indeed a system in jeopardy. The major source of the threat to its proper functioning is the increasing pressure to perform tasks that either do not require doing, could be done better by others, or could be done more efficiently using expedited review procedures.” Fost and Levine, JAMA, 2007