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Comments on NPRM amendments to the Common Rule.

 

Jerry Menikoff, MD, JD
Director, Office for Human Research Protections
Department of Health and Human Services
1101 Wootton Parkway, Suite 200
Rockville, MD 20852

January 2, 2016

Regarding docket number HHS-OPHS-2015-0008 on www.regulations.gov: Comments on NPRM amendments to the Common Rule.

Dear Dr. Menikoff:

We, the undersigned, organized by Genetic Alliance, offer the following comments. Genetic Alliance is a nonprofit health advocacy organization with a 29-year track record of engaging individuals, families, and communities to transform health. Genetic Alliance is a network of more than 1,200 advocacy organizations as well as thousands of universities, private companies, government agencies, and public policy organizations.

Overall impressions
We think that this NPRM does not meet the standard of a proposed Rule, since it raises more questions than the ANPRM that preceded it four years ago. This NPRM is not responsive to most of the issues that many organizations raised in 2011. In general, the NPRM lacks the clarity and precise definitions and concepts required by an NPRM. Instead, the document states that the agency will develop critical elements in the future, rather than offering them here as part of the NPRM. The resulting Final Rule will cause confusion and unintended consequences that will not protect research participants, nor further the benefits of research.

We agree that “science has continued to advance, as has the dialogue regarding the changing nature of research and the preferred balance of protections for research participants among the principles of respect for persons, beneficence, and justice.” In fact, we recommend that the terms ‘subject’ and ‘patient’ be replaced with the term ‘participant’ for all references to individuals in research. In fact, the Common Rule should refer to human participants, not human subjects. Employing the term “human subjects” denigrates participants’ involvement as essential partners in these critical aspects of biomedical research. Likewise, labeling participants ‘patients,’ continues to assign us a passive role and undercuts the very dignity and respect the NPRM aims to instill throughout updated research regulations. Employing the term ‘participant’ recognizes agency and autonomy. President Barack Obama and the National Institutes of Health Director, Francis Collins, have gone on record declaring that individuals engaged in research are partners and participants, not subjects or patients, and we recommend these terms as well.

Informed consent should be simple and offer more meaningful, culturally appropriate engagement
We agree with the NPRM’s recommendation to shorten and simplify consent forms; we particularly applaud the emphasis placed on meaningful choices and decisions informed by pertinent information “a reasonable person would want to know”. We believe that is contextual.

The Common Rule should recognize consent as a process, and not a translational form. A form, particularly one is not responsive to context cannot not be meaningful. In the process of shortening and simplifying consent forms, we recommend the Common Rule support and enable culturally and clinically appropriate consent processes — these should be contextually appropriate. The Common Rule should also rely on the Fair Information Practice Principles, and employ other relational methods of engaging individuals in research.

We recommend including the proposed notifications of potential commercial profit, of return of clinically relevant results, and of possibilities for re-contact, as standard procedure in consent forms unless researchers can justify their omission through documented approval from an appointed oversight professional or participating IRB. We also recommend that results are returned in accordance with the preferences of the participant and in the context of their family, community, and situation.

The provision regarding allowable waivers of signatures with cultural groups in which signatures are not normally employed is a reasonable provision in that it acknowledges the specific needs of various cultures. However, it assumes that researchers can sufficiently evaluate cultural norms and make culturally appropriate judgments regarding minimal risk. To preserve justice, beneficence, and proper respect for participants’ autonomy, we advise that a waiver of signature should only be permitted after documented consultation with a recognized cultural expert and/or the community under consideration.

Broad informed consent for primary and secondary research conducted on biospecimens and for the storage of biospecimens and identifiable private information is not sufficient for responsible participant engagement We agree that biospecimens should be afforded the same protections as other information from human research participants with consent required for inclusion in research.

However, we have reservations about the use of broad consent for biospecimens-related research as described in the NPRM. Broad consent is a valid option, but should not be the only option. The NPRM fails to provide clear definitions of broad consent and how and when it should be used. As described, it appears to be a binary choice, which denies participants autonomy and respect.

Broad consent would exclude participants who might hesitate to include their specimens in secondary research for which they had insufficient knowledge. This could be, for example, out of fear the research may conflict with certain religious beliefs or other convictions. It might also prevent participants from choosing to share their biospecimens more broadly than solely in one institution or study.

It has been documented through numerous studies that participants prefer to be offered relevant information, granular choices, the opportunity to withdraw, and research results. Broad, one-size-fits-all, consent, cannot achieve these goals.

We are aware that there is resistance to even broad consent for biospecimens, let alone dynamic and granular consent. Researchers and institutions are concerned that the added costs and complications will be prohibitive. We suggest that 1) the value of engaging participants trumps cost and convenience, 2) consent does not equal engagement, 3) true engagement might include notification, ongoing communications, and various kinds of consent processes. Various technologies can now support novel methods of engagement and decrease associated costs and time. For example, the Reg4ALL, based on the Platform for Engaging Everyone Responsibly (PEER), enables community based, contextual, granular, dynamic consent for much lower costs than traditional written paper consent .

NPRM exclusions and exemptions in general support improved research and participant engagement, subject to certain concerns
The systematic changes described in the NPRM could have the inadvertent effect of encouraging researchers to design studies eligible for exemption or exclusion, and discourage researchers from planning more rigorous and involved human research due to the perceived “penalty” of needing to undergo IRB review.

Common Rule exclusions
We find most of the exclusions listed sensible, though we hesitate to allow the determination of exclusion to rest primarily on researchers’ judgment. Studies excluded from oversight under the Common Rule should still be reviewed with some regularity by someone other than the principal investigator. IRBs generally have a great deal of experience and skill in dealing with the possibility of exemption and should be consulted, albeit in a streamlined process.

Invoking HIPAA to convey privacy and security protections is illogical since HIPAA regulations specifically do not apply to de-identified biospecimens.

Additional categories of exempt research
It seems peculiar to leave enormous gaps in processes for determining exemption and relegate these uncertainties to a Rule. As written, determination of exemption would depend on web-based tools that are not yet developed. These tools should be developed before becoming part of the Rule.

Moreover, these tools will depend on accurate input for success. Oversight should be built in, not necessarily as much to check exemption status but to verify the accuracy of the information provided in order to secure exemption. While it could be acceptable for researchers to provide the information determining their work’s status either to the proposed tool or to an oversight expert, it would be possible for researchers to contrive their answers to secure exempt status in either case. An outside auditor therefore seems advisable. Notification given to participants of exempt status is also advisable.

The exemption for the secondary use of identifiable private information is confusing and lacks specificity. The term ‘identifiable private information’ is not well defined, and may be at odds with similar definitions in federal laws, rules, and acts. This creates a troublesome lack of harmonization.

Guidelines around obtaining a waiver of consent require further clarity
A waiver of consent for biospecimens research may make sense in certain contexts. We are concerned about instances of researchers wishing to take advantage of this waiver, However, the NPRM states that these instances are intended to be “extremely rare”, without precisely defining how rare or who will have authority to grant such a waiver, including exercising the oversight to ensure that waivers are, overall, indeed “rare” in practice. From the point of view of the institution this might signal that this waiver should almost never be used. For the participant, ‘rare’ lacks specificity and might elicit distrust.

The current requirements stipulate that waivers will only be considered for work that is scientifically compelling and that cannot secure consented biospecimens. Again, this creates an incentive for researchers to argue for the difficulty of obtaining consent. There should be clear guidelines about the characteristics of situations in which a waiver is appropriate.

Using a single IRB for multi-site collaborations should be optional
A single IRB for multi-site collaborations should be context dependent, since experts have argued both that it might either relieve or impose greater burden on researchers. There are a number of models of efficient use of IRBs in multi-center studies. It is not clear from the NPRM whether the agency means an IRB of record with associated reliance agreements, or a true ‘single’ IRB. We recommend refining systems that accelerate study review and conserve resources. Just as engagement should be contextual, the needs of various communities with regard to oversight should be carefully considered with the ultimate goal of improving research processes for the sake of research participants.

Eliminate continuing review when appropriate
We agree with the proposition to eliminate continuing review and posit that regularly maintained and updated documentation establishing research progress (and subject to random audits) is sufficient.

All clinical trials should be subject to the Common Rule
We heartily approve of this amendment, as it creates more consistency across regulations that would uniformly promote responsible participant engagement.

Summary: The Common Rule is of paramount importance in protecting research participants while also promoting research—in this historic shift to modernize the Common Rule, the NPRM should take advantage of the opportunity to support responsible participant partnership, choice, and engagement. No Rule should be finalized without sufficient engagement, and responsiveness to the recommendations, of the community that participates in research: patients, participants, families, communities, providers, investigators, and health systems. Various agencies within Health and Human Services are using modern methods of robust engagement that the Office of Human Research Protections should avail itself of before any rule is finalized. It is our opinion that this NPRM has a long way to go before it is finalized.

Sincerely,

Organizations:

AliveAndKickn Haworth New Jersey
Alstrom Syndrome International Mount Desert Maine
American Association for Respiratory Care (AARC) Irving Texas
American Behcet's Disease Association (ABDA) Rochester Michigan
American Multiple Endocrine Neoplasia Support Maryville Tennessee
Angioma Alliance Norfolk Virginia
Association of Gastrointestinal Motility Disorders, Inc. (AGMD) Bedford Massachusetts
Beautiful You MRKH Foundation, Inc. Bethesda Maryland
CADASIL Together We Have Hope Non-Profit Org Round Rock Texas
Center for Medical Technology Policy Baltimore Maryland
Children's PKU Network Encinitas California
Christopher and Dana Reeve Foundation Short Hills New Jersey
Colorado Developmental Disabilities Council Denver Colorado
Council for Bile Acid Deficiency Diseases Rockville Maryland
Cure HHT Monkton Maryland
Cutaneous Lymphoma Foundation Birmingham Michigan
Detroit Medical Reserve Corps Detroit Michigan
Dyskeratosis Congenita Outreach, Inc. New York New York
Everyminute.org Old Hickory Tennessee
Family Voices NJ Newark New Jersey
Fight Colorectal Cancer Washington District of Columbia
FOD (Fatty Oxidation Disorders) Family Support Group Okemos Michigan
Geneforum.org; Genomics for Everyone Portland Oregon
Hannah's Hope Fund Rexford New York
HCMA Denville New Jersey
Hemophilia Federation of America Washington District of Columbia
Hepatitis Foundation International Silver Spring Maryland
ICAN, International Cancer Advocacy Network Phoenix Arizona
Immune Deficiency Foundation Towson Maryland
InnoThink Center for Research in Biomedical Innovation Indianapolis Indiana
International Foundation for Autoimmune Arthritis St.Louis Missouri
Joubert Syndrome & Related Disorders Foundation Cincinnati Ohio
Law Office of Robert S Chase Fall River Massachusetts
Lupus and Allied Diseases Association Verona New York
M-CM Network Chatham New York
MLD Foundation West Linn Oregon
National Multiple Sclerosis Society Washington District of Columbia
NBIA Disorders Association El Cajon California
Organic Acidemia Association Golden Valley Minnesota
PPD Wilmington North Carolina
PXE International Washington District of Columbia
QE Philanthropic Advisors Potomac Maryland
RASopathies Network USA Altadena California
Statewide Parent Advocacy Network Newark New Jersey
Sudden Arrhythmia Death Syndromes (SADS) Foundation Salt Lake City Utah
The Moebius Syndrome Foundation Pilot Grove Missouri
The National Adrenal Diseases Foundation Great Neck New York
The TMJ Association Milwaukee Wisconsin
The Ultra Rare Disease, Disorders & Disabilities Foundation Belfast Northern Ireland
Trisomy 18 Foundation Dale City Virginia
United Mitochondrial Disease Foundation Pittsburgh Pennsylvania
Zephyr L.T.N.P Foundation, Inc. Sacramento California

 

Individuals:

Misha Angrist Durham North Carolina
Terry Anschutz Stoughton Wisconsin
Dixie Baker Redondo Beach California
Geri Barish Baldwin New York
Diana Bianchi Boston Massachusetts
Rhonda Brown-Kehoe Foster Rhode Island
Alexis Caldwell Richmond Virginia
Christine Carter Brookeville Maryland
Audrey Chapman,Ph.D Farmington Connecticut
Thomas Cheng Torrance California
Michael Chou Boston Massachusetts
Kristin Clift Jacksonville Florida
Donna Cline Birmingham Alabama
Siobhan Dolan Bronx New York
Jennifer Dugan Rochester Minnesota
William Ebomoyi Chicago Illinois
Laurel Evans Vancouver BC Canada
Ruth Evans Washington District of Columbia
Marilyn Field Lexington Kentucky
Jaime Frias Tampa Florida
Joyce W. Graff Brookline Massachusetts
Nancy Green Briarcliff New York
Judith Grillo Columbia Maryland
Lisa Helms Guba, RN Annapolis Maryland
Peter Harris Loveland Colorado
Robert Hinton Cincinnati Ohio
Diane Houle Waterbury Connecticut
Jeffrey Joyce Marshfield Wisconsin
Jessica Law Baltimore Maryland
Robin Leger, RN,MS,PH.D Gardner Massachusetts
Kaitlin Lovett Baltimore Maryland
Erika Lutins Washington District of Columbia
John Mattison San Diego California
Bertha Mo San Francisco California
Cherie Mohan Abingdon Maryland
William Nowell Upper Nyack New York
Anne Nyberg Old Lyme Connecticut
Stephanie O'Neil Cambridge Massachusetts
Kathleen Palmer Baltimore Maryland
Mary Pendergast Washington District of Columbia
Kimberly Noble Piper Des Moines Iowa
Laurel Pracht Sun City Arizona
Michele Puryear Takoma Park Maryland
William Read Phoenix Arizona
Heidi Rehm Westborough Massachusetts
Diane Seibert Washington District of Columbia
Christian Simon Iowa City Iowa
Blair Stevens Houston Texas
Mary Teresi Iowa City Iowa
Jennifer Wagner State College Pennsylvania
Robert West Syracuse New York
Susan Winterbottom Milton Delaware
Rina Wolf Valencia California
Mark Yarborough Sacramento California
Alexander Wait Zaranek Boston Massachusetts

 

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