October 11, 2016 - Massachusetts General Hospital

Dear Dr. Orf:

Thank you for your January 29, May 10 and May 25, 2016 reports in response to our December 17, 2015, March 17 and April 26, 2016 requests for information relating to the human subjects protection program at Massachusetts General Hospital (MGH) to evaluate compliance with Department of Health and Human Services (HHS) regulations for the protection of human research subjects (45 CFR part 46). This is part of our not-for-cause evaluation program at OHRP. We reviewed 25 informed consent documents, minutes of the most recent IRB meetings, written IRB policies and procedures, IRB guidelines for investigators involved in human subjects research, and other documents. Based on our review of your response, we make the following determinations and make further recommendations:

A. Determinations regarding institution’s system for protecting human subjects:

1. In our December 17, 2015 letter we expressed concern that the verbal informed consent pre-screening processes reviewed and approved by MGH for multiple protocols did not include all required elements of informed consent, such as: the purpose of the research, the procedures and risks of the screening, how confidentiality was maintained, and whom to contact with questions regarding the research and subjects’ rights. We noted such deficiencies in the following protocols, among others:

a. Protocol 2011P001098: IGF-1 and Bone Loss in Women with Anorexia Nervosa
b. Protocol 2012P001806: Lymph Node Excision Protocol
c. Protocol 2012P000656: Targeted Pharmacological Interventions for Autism. A Double-Blind, Placebo-Controlled Study of Atomoxetine in Children and Adolescents with Autism
d. Protocol 2012P001897: Imaging Molecular Pathology of Diabetes with PET
e. Protocol 2012P002605: The Glycemia Reduction Approaches in Diabetes. A Comparative Effectiveness Study
f. Protocol 2013P000513: Investigation of female reproductive hormone dynamics during adolescence

We have determined that the informed consent processes for the studies identified above did not meet the regulatory requirements at 45 CFR §§ 46.116(a) (1), (2), (5), and (7) which require, in part, that when seeking informed consent a description of the procedures to be followed and a description of any reasonably foreseeable risks and discomforts, in language understandable to the subject, shall be provided to each subject.

Corrective actions: We acknowledge your January 29, 2016 letter which indicated the following corrective actions:

i. The guidance document “Pre-Screening of Research Subjects during Recruitment” will be revised to include the requirement for the investigator to obtain informed consent of potential subjects prior to the collection of any information about them. The guidance will state that the IRB may waive the requirement for the investigator to obtain a signed consent form and allow the investigator to obtain verbal consent for the pre-screening activities.

ii. The guidance document “Pre-Screening of Research Subjects during Recruitment” will be revised to include the requirement for pre-screening telephone scripts to include statements such as the following:
• Thank you for your interest in our research study [briefly describe purpose].
• Is this a good time to talk?
• Would you be willing to answer questions about your health and medical history to find out if you might qualify for the study? [if appropriate add statement “Some of the questions may make you feel uncomfortable.”] You can stop at any time.
• I will record your answers in writing, but only collect detailed contact information if you qualify for the study and want to schedule an in person visit.
• Optional Statement: I will also ask you for your [indicate what information will be collected, e.g., date-of-birth, social security number and medical record number] to register you with the hospital before your in person visit.
• The risk of allowing us to collect and record your name with your answers is a loss of confidentiality. We will take reasonable steps to protect the confidentiality of your information.
• May I begin?

iii. The IRB review checklists will be updated to include documentation of findings relative to the informed consent process for telephone pre-screening activities to ensure that review of the consent process is documented in IRB records.

iv. The updated guidance and review checklists will be reviewed with the IRB chair/reviewers.

v. Once the updated guidance is finalized and posted to the Partners intranet research website which is available to investigators, research staff and IRB members (Research Navigator); the Partners Human Research Office will send an email bulletin to all principal
investigators and research staff as well as IRB members to inform them of the changes to the guidance.

vi. Revised pre-screening scripts including the above information have been reviewed and approved by the IRB for studies that are still enrolling subjects.

B. Recommendations:

We recommend that the guidance document “Pre-Screening of Research Subjects during Recruitment” also include information regarding whom to contact with questions about the research or the subjects’ rights, to ensure that this required element of informed consent is provided to subjects. 45 CFR 46.116(a)(7).

We recommend that the guidance document “Pre-Screening of Research Subjects during Recruitment” also include the circumstances under which IRBs are permitted to waive the requirement for an investigator to obtain a signed consent form for some or all of the subjects. 45 CFR 46.117(c)(1)-(2).

Your responses adequately addressed our remaining concerns. At this time, there should be no need for further involvement by our office regarding the determinations and resolved concerns. Please notify us if you identify new information which might alter this conclusion. Please feel free to contact me if you have any questions.

We appreciate your institution’s continued commitment to the protection of human research subjects.

Sincerely,

Kristina C. Borror, Ph.D.
Director, Division of Compliance Oversight
101 Wootton Parkway, Suite 200
Rockville, Maryland 20852
Telephone: 240-453-8132
FAX: 240-453-6909
E-mail: Kristina.Borror@hhs.gov

Kemnique Ramnath, MHA
ORISE Fellow
Division of Compliance Oversight
1101 Wootton Parkway, Suite 200
Rockville, Maryland 20852

cc:
Maria Sundquist, MPA, Partners Human Research Committees
Avram Traum, Massachusetts General Hospital IRB #1
A. Robert Schleipman, Massachusetts General Hospital IRB #2
David Smith M.D., Massachusetts General Hospital IRB #3

Dr. Joanne Less, Food and Drug Administration (FDA)
Ms. Bridget A. Foltz, FDA
Dr. Michelle Bulls, Director of OPERA, Office of Extramural Research, NIH
Dr. Sherry Mills, National Institutes of Health (NIH)
Ms. Sarah Carr, Office of Science Policy, NIH