Month: May 2019

HHS/FDA Proposed Deregulations: Recommendations for HIPAA and IRB’s approval and informed consent process

By Colleen Sproul

The US Executive Branch’s  Spring 2019 Unified Agenda of Regulatory and Deregulatory Actions is out, and HHS/FDA have identified for deregulation, among other things, the current IRB approval process in order to allow any U.S. clinical site to rely on the approval of just one IRB in order to conduct a study at that site.  All proposed rule changes were made by the agency in response to the Administration’s request for all agencies to identify “ineffective regulations” and propose deregulations to meet the Administration’s objectives to streamline and improve “cost effectiveness” (although it is not clear whether it is HHS that would see economic benefit).  

Institutional Review Board Proposals

  • Title: Institutional Review Boards; Cooperative Research 
    • Abstract: This proposed rule would replace current FDA requirements for cooperative research such that any institution located in the United States (U.S.) participating in multisite cooperative research would need to rely on approval by a single Institutional Review Board (IRB) for that portion of the research that is conducted in the U.S., with some exceptions.  This proposed rule would also establish an IRB recordkeeping requirement for research that takes place at an institution in which IRB oversight is conducted by an IRB that is not operated by the institution.

  • Title: Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations
    • Abstract: This proposed regulation would permit an Institutional Review Board (IRB) to waive or alter the informed consent requirements under certain conditions for minimal risk clinical investigations. This would facilitate certain minimal risk clinical investigations to support the development of new products to diagnose or treat disease and would harmonize with the HHS Common Rule waiver provision that has been adopted and successfully employed by other agencies. This proposed regulation is intended to aid patient access to new products by facilitating investigators’ ability to conduct studies that may contribute substantially to the development of products to diagnose or treat diseases or conditions, or address unmet medical needs.

Health Insurance Portability and Accountability Act of 1996 (HIPPA) Proposals

Also proposed is the “removal of barriers” created by HIPAA compliance, which is especially interesting in light of the fact that, in 2018, the Office of Civil Rights set an agency record in HIPAA enforcement activity by levying fines totaling $28.7 million (against MD Anderson, Boston Medical Center and Brigham’s and Women’s Hospital and MGH, among others).   All proposed rule changes were made by the agency in response to the Administration’s request for all agencies to identify “ineffective regulations” and propose deregulations to meet the Administration’s objectives to streamline and improve “cost effectiveness” (although it is not clear whether it is HHS that would see economic benefit).

  • Title: HIPAA Privacy; Changes to Support, and Remove Barriers to, Coordinated Care
    • Abstract: This proposed rule would publish for comment proposals to modify provisions of the HIPAA Rules which present barriers that limit or discourage coordinated care and case management (including care coordination challenges arising from the opioid crisis) among hospitals, physicians (and other providers), payors, and patients, or otherwise impose regulatory burdens that may impede the transformation to value-based health care without providing commensurate privacy or security protections for patients’ protected health information (PHI) and while maintaining patients’ ability to control the use or disclosure of their PHI and to access PHI. This proposed rule would subsume the previous 0945-AA09 entry in the Regulatory Agenda.

Other HHS/FDA Proposals

The Office of Management and Budget’s Office of Information and Regulatory Affairs website has a synopsis of each regulation identified for “deregulation” by HHS/FDA, but the links to the meeting minutes for each proposal are inactive and the webpages with proposals under the Fall 2018 Unified Agenda are no longer active on the FDA website; it is not possible at this time to substantively review and compare the data (some of the HHS Spring 2019 proposals are updates to 2018 proposals) via the web.  Below is a list of changes we’ll be tracking as more information is made available as part of the public comment period:

  • Title: Definition of the Term “Biological Product” 
    • Abstract: The Food and Drug Administration (FDA) proposes to amend its regulation that defines biological product to conform to the statutory definition (21 U.S.C. 262) adopted in the Biologics Price Competition and Innovation Act of 2009. 
  • Title: ●HHS Policy for the Protection of Human Research Subjects: Update to Subpart E (IRB Registration) 
    • Abstract: This rule would amend subpart E of 45 CFR part 46 (Institutional Review Board (IRB) Registration) to align subpart E with recent amendments to the basic HHS Policy for the Protection of Human Subjects (subpart A of 45 CFR part 46, also known as the Common Rule) and to give effect to one of the policy goals of the subpart A revision (i.e., eliminating unnecessary administrative burden on IRBs and institutions regulated under 45 CFR part 46). The general compliance date of amendments to subpart A of 45 CFR part 46 was January 21, 2019.
  • Title: Part 50 Protection of Human Subjects and Part 56 Institutional Review Boards
    • Abstract: This proposed rule would harmonize, to the extent practicable and consistent with other statutory provisions, several sections certain provisions of FDA’s regulations on human subject protection and institutional review boards with the recently revised “Federal Policy for the Protection of Human Subjects” (the revised Common Rule (45 CFR 46, subpart A)). The rule also proposes minor amendments to related regulatory provisions.
  • Title: Updates to 1974 Privacy Act Regulations
    • Abstract: This rulemaking will update regulations at 45 CFR part 5b, which detail how the Department implements requirements of the Privacy Act of 1974, as amended (5 U.S.C. 552a).

Public Review is Open for Comment: ICH Draft Revision of Guideline on General Trial Design and Conduct

By Colleen Sproul

The draft 2020 ICH(E8)R1 is three times the length of the original and is available for Sponsor comment. The ICH has taken its many years of data and identified principles which, among other things, will facilitate the acceptance of sponsor data worldwide, help ensure subject recruitment by involving subjects in study design and placing an emphasis on quality at every step of a trial.

Patient Input into Study Design

Patient organizations have already weighed in the updated Guideline reflects this critical input. Designing a study which fits the patients’ lifestyle (considering their disease state), will ensure that the drug itself will be better tailored to the population that will actually use the drug, post-approval.  From ICH(E8)(R1) 2.3:

“Involving patients at the early stage of study design is likely to increase trust in the study, facilitate recruitment, and promote adherence, which should continue throughout the duration of the study. Patients also provide their perspective of living with a condition, which contributes to the determination of endpoints that are meaningful to patients, selection of the right population, duration of the study, and use of the right comparators.”

Investigator Input into Study Design

ICH(E8)(R1) offers very early-stage study planning guidance and, not unexpectedly, it has found that reliance on just a few key opinion leaders for study design has to be augmented by opening the study to challenge by other subject matter experts: subjects and the potential investigators. From ICG(E8)(R1) 3.3.3:

“Clinical investigators and potential study subjects have valuable insights into the feasibility of enrolling subjects who meet proposed eligibility criteria, whether scheduled study visits and procedures may be overly burdensome and lead to early dropouts, and the general relevance of study endpoints and study settings to the targeted patient population”

Create a Sponsor Culture that Supports Open Dialogue

Interestingly, the ICH has identified a critical Sponsor success factor as “Establishing a Culture that Supports Open Dialogue” [ICH(E8)R1, 3.3] by rewarding team and individual critical thinking and encouraging open dialogue to go beyond “reliance on tools and checklists”. From the Guideline:

“Choose quality measures and performance indicators that are aligned with a proactive approach 169 to design. For example, an overemphasis on minimising the time to first patient enrolled may result in devoting too little time to identifying and preventing errors that matter through careful design.”

And:

“Study designs should be operationally feasible and avoid unnecessary complexity and unnecessary data collection. Patient consultation early in the study design process contributes to these factors and would be likely to result in fewer protocol amendments.”

Deemphasize Factors Such as First-Patient-In

The Guideline suggest that shifting team focus onto high-level quality goals in the planning stages, as opposed to micro-goals tied to enrolment, will contribute to overall study success:

“Choose quality measures and performance indicators that are aligned with a proactive approach to design. For example, an overemphasis on minimising the time to first patient enrolled may result in devoting too little time to identifying and preventing errors that matter through careful design.”

And:

“Consider whether nonessential activities may be eliminated from the study to simplify conduct, improve study efficiency, and target resources to critical areas.” [ICH(E8)(R1) 3.3.2]

Guidance on Operational Criteria

The Guideline provides Sponsor guidance to help achieve another critical success factor:  proactive, routine communication of changing study priorities and ongoing risks mitigation activities to its study sites, as site understanding of priorities and necessary resource allocation will enhance the correct implementation of a study protocol (ICH E8(R1). One possible solution would be implementation of sub-program management team, with an emphasis on crafting routine communication to update investigators on the changing study priorities (outside of the Protocol) and any operational issues such as drug availably, delays in safety reporting by other study sites and whatever else a sponsor may think a site needs to know to increase its investigators knowledge of the drug.

The draft is currently under public consultation. Stakeholders may submit comments or questions to step2comments@ich.org

Read the draft guideline here: https://bit.ly/2Jyzzjl