2005 Important Updates to SBU's Human Subject Protections Program (HSPP)
Released October 24, 2005
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Our Human Subject Protection Program (HSPP) has many active participants, including Principal Investigators and their study teams, staff of the Office of Research Compliance (ORC), and the membership of our Institutional Review Boards (IRB). Our combined efforts continue to help ensure that our HSPP is solid and effective in keeping safe those individuals who volunteer to participate in our research activities at SBU.
The ORC and the IRBs are constantly evaluating the program to assess the need for clarifications of current SBU policies and procedures, promulgation of new policies and procedures, and dissemination of new federal guidance and regulations. The following is a summary of such actions that have been taken or proposed over the past year, including some clarifications of unchanged policies and procedures, since our last update in 2004.
I. Research Involving Prisoners as Subjects Now Possible at SBU
Recently, CORIHSb was fortunate enough to add as a new IRB member an individual who meets the federal requirement as a ‘prisoner representative’. This means that the committee is now properly constituted to review research involving prisoner subjects, in accordance with federal regulations at 45 CFR 46, subpart C at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartc
A prisoner is defined as “any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under a criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution, and individuals detained pending arraignment, trial, or sentencing.” A prisoner can be an adult OR minor (“juvenile offender”) meeting the above definition.
If you are interested in learning more, please also review the guidance made available from the federal Office of Human Research Protections (OHRP) at http://www.hhs.gov/ohrp/humansubjects/guidance/prisoner.htm and feel free to contact me to discuss the additional protections that are required when proposing use of prisoners in research activities. Be advised that Section 11 of the CORIHS Handbook for Investigators will be revised to reflect this major change in our policies and procedures.
II. Importance of Documentation in Human Subjects Research/New Submission Requirement for Research Involving More than Minimal Risk
One of the frequent findings from the ORC’s QA/QI Program for Investigators is a lack of appropriate documentation. Compliance with federal and local regulations is only a part of your responsibilities as an investigator; you must also be able to prove your compliance…through documentation. ORC and the IRBs are well aware of this responsibility, as documentation is the only variable considered when their procedures and performance are audited by OHRP and FDA. The famous audit phrase is, of course, ‘If it isn’t documented, it didn’t happen.
If ORC, OHRP or FDA (as applicable) were to review the files in which you record information about the subjects who have participated in your research, it should be obvious that the subject consented to participation (a signed consent document, at the very least, if not a file note that capacity was assessed, study discussed with potential subject etc.) and that you followed your approved protocol, i.e., each subject met the study’s eligibility criteria and each subject participated in the research procedures in the type and frequency approved by the IRB. If the information is not documented, how can a reviewer of your files know that the subject consented, was eligible for participation, and that only approved research procedures were conducted?
To this end, please be aware that the IRBs now require that application submissions of studies involving more than minimal risk to the subject must include an inclusion/exclusion criteria checklist to be completed and kept on file for each subject who has consented to be in the study. The checklist should include enough information for each criterion (e.g., a range of acceptable values etc.) to allow an auditor to confirm the subject’s eligibility (or ineligibility, as applicable).
III. What Does it Mean When the IRB Requires Assent of Minor Subjects?
When your research proposes involvement of subjects who are under the age of 18 years old, there are additional protections that must be in place in order to conduct the study. These are addressed in the federal regulations at 45 CFR 46, subpart D, at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#subpartd. One of the possible protections afforded to children in the requirement to obtain their assent in most instances (for discussion on when the IRB can waive the assent requirement, see 46.408[a]). ORC has written guidance on the assent requirement, and has provided it with approval documents to investigators including minors in their research populations. One of the important aspects of the guidance is to point out that when the IRB requires assent of the minor subjects, it means that verbal assent must be obtained for children starting at ages 8-9 years old, and documented assent (via an IRB approved assent document) must be obtained starting at around ages 11-12 years old. In the former case of verbal assent, the investigator should document in his/her research records that he/she has conducted the assent process, along with the outcome (i.e., did the child agree or disagree to participate). Where the IRB has required assent, if the child does not assent, the child is not to be enrolled in the study (regardless of the parent/guardian’s wishes). If your research involves minors as research subjects, please review this guidance document at http://www.stonybrook.edu/research/humans/minorassent.html
IV. Inclusion of Wards of State (e.g., Foster Children) in Research Activities
Be advised that if the IRB approves research involving minor subjects under federal category 45 CFR 46.406 (i.e., Research involving greater than minimal risk and no prospect of direct benefit to individual subjects, but likely to yield generalizable knowledge about the subject's disorder or condition), then wards of state may not be enrolled in the research activity without first obtaining approval from the IRB. Additional protections (addressed in 46.409) must be in place prior to inclusion of these children.
V. Justifying and Keeping Track of the Number of Human Subjects
The IRB’s would like to clarify for investigators that the number of subjects that needs to be statistically justified in new studies is the # of subjects required to answer the research hypothesis, i.e, the number needed to complete the study. For multicenter studies (pharmaceutical, National Oncology Groups etc), the number to be justified is the total #, across all sites, required to answer the research hypothesis. The # expected to enroll locally, does not need to be justified because in most instances the # is dependent upon the probability of patients presenting in the clinic etc. who have the disease/disorder in question.
Nonetheless, Investigators do need to track post-consent statistics of:
• Subject screen failures (i.e., # of subjects who failed to meet study eligibility requirements via screening procedures conducted after consent has been obtained). The subject record should contain documentation as to how the subject failed the screening procedures.
AND
• Subject withdrawals and removals. The subject record should contain documentation as to why the subject withdrew or was removed; this information needs to be reported to the IRB at the time of continuing review.
VI. Inclusion of Non-English Speaking Human Subjects in Your Studies
It is consistent with the ethical principle of justice, one of three principles that guide us in the conduct of human subjects research (see the “Belmont Report”, that any person who meets the eligibility criteria for a research activity in which there is a possibility of therapeutic benefit should be invited to participate. It would be unethical to turn that individual away if she or he did not happen to speak English, particularly given the population of the patients at our University Hospital.
Although Section 12 of the CORIHS Handbook for Investigators currently describes 2 consent procedures that may be followed when inclusion of non-English speaking subjects is proposed (again, it is strongly urged that research activities involving the possibility of therapeutic benefit be written to include non-English speakers), a recent policy decision by the 2 CORIHS committees has endorsed sole use of the first method for studies involving more than minimal risk:
The IRB-approved, English version of the consent form can be translated into the foreign language. An affidavit of accurate translation must be provided from an appropriate translator who is unaffiliated with the study. The translated consent form and affidavit must be submitted and approved, as an amendment to the approved study, by CORIHS before use of the consent form.
Note that the second consent procedure, utilizing the ‘short form’ method, described in detail at http://www.hhs.gov/ohrp/humansubjects/guidance/ic-non-e.htm, is now only allowed to be used at SBU for minimal risk studies.
If you are planning on conducting international research, you will want to review OHRP’s International Compilation of Human Subject Research Protections, available at http://www.hhs.gov/ohrp/international/index.html#NatlPol (list of included countries commences on page 5 once the compilation is accessed). According to OHRP, this document “encompasses 72 countries, lists standards issued by international organizations, includes updated information for General and Drug research, and provides a listing of the laws, regulations, and guidelines on privacy/data protection, human biological materials, and genetic research. The Compilation now provides over 400 direct web links to each country's key organizations and laws, whenever available. OHRP believes this Compilation will help IRBs, researchers, and others to meet regulatory requirements to assure that research studies comply with applicable standards.”
VIII: New Clinical Trials Registry Requirement
As first reported in Dr. Habicht’s e-publication, The Monday Memo, The International Committee of Medical Journal Editors (ICMJE; http://www.icmje.org) has recently set policy that mandates registration of clinical trial studies in a “publicly held registry” in order to be eligible to submit a clinical trials-related manuscript for publication in an ICMJE member journal.
The ICMJE definition of a clinical trial is one in which there is “prospective assignment of human subjects to intervention or comparison groups to study the cause- and-effect relationship between a medical intervention and a health outcome.” Further, the ICMJE has defined criteria for what constitutes an acceptable registry; as an example, the registry at http://clinicaltrials.gov satisfies those criteria.
If you are an investigator of a pharmaceutical company-initiated clinical trial, you do not have to register the study, as it is the responsibility of the pharmaceutical company to register all trials that they initiate. However, Investigator-initiated clinical trials must be registered by the Investigator him/herself (regardless if pharma-sponsored, NIH-sponsored etc). Studies enrolling subjects after July 1, 2005 must adhere to this requirement and any applicable trial initiated prior to July 1, will need to be registered immediately (ICJME set a deadline for this latter group of September 13, 2005). Note that the CORIHS application has recently been updated to reflect this requirement as well.
IX: Gentle Reminder #1: What Research Activities Require Submission of a CORIHS Application to ORC
Good Question. First, let’s define research. If:
• You plan collect data systematically,
and
• Your intent is to contribute to generalizable knowledge (in other words, you plan on sharing your findings to those OUTSIDE of the SBU campus community),
then you are conducting research. You may ask: What about QA/QI activities? Well, such activities are systematic investigations, but are not considered research (or under the jurisdiction of CORIHS) if the QA/QI data are not presented or published outside of the University (i.e., not contributing to generalizable knowledge). However, CORIHS approval is required before QA/QI data are prepared for publication and/or presentation outside the University.
So, when does research become ‘research involving human subjects’ requiring application to, and approval by, CORIHS?
At this institution, if your research plan involves intervening with humans, or if you are collecting and/or receiving and/or analyzing human tissue or human data, then an application must be submitted and approved prior to the commencement of the activity.
There are 2 types of CORIHS applications. If your study involves ‘no foreseeable risk’, and involvement of human subjects is described in one of the exemption categories listed under Section 2, then you can submit the exemption application, to the Office of Research Compliance (ORC). ‘Exempt’ in this case means ‘exempt from IRB review’, but not exempt from Institutional review, which is why such applications are reviewed and handled by the staff of ORC, on behalf of SBU.
All other activities (those involving minimal risk and qualify for expedited review, in accordance with the categories provided at Section 2, as well as all studies that don’t qualify for exempt or expedited review, and must be reviewed by the full committee), require completion and approval of the Human Research application.
X: Gentle Reminder #2: What do You Need to Track and Report in Terms of ‘Adverse Events’
CORIHS-approved investigators are responsible for prompt reporting to the IRB of “any unanticipated problems involving risks to subjects are others…” This section seeks to clarify reporting requirements for a specific type of unanticipated problem, the serious adverse event. Full discussion of these requirements, including specific definitions, are addressed in Section 16.E of the CORIHS Handbook for Investigators
• If the adverse event is serious, unanticipated, and there is a reasonable possibility that the event was caused by the subject’s participation in the study (i.e., not caused by expected disease progression or clinically-indicated treatment outside of the research activity), then the event must be reported to the IRB immediately (i.e., within 5 working days).
• Adverse events that are serious but anticipated, though not requiring immediate reporting, must be reported to the IRB at the time of continuing review in summary format (provided either from the PI for ‘on-site’ AE’s, or from the sponsor for ‘off-site’ AE’s). The IRB will defer review on continuing review applications that lack this summary.
XI. The ORC Website has all the current information and current applications you need:
http://www.stonybrook.edu/research/humans/humansubjects.html
As you can see from this update, our Human Subject Protection Program (HSPP) is always undergoing review to ensure that SBU is following the best possible practices in protecting our subjects. The best way to stay up to date with changes made to our HSPP is to visit the website often. When you need to complete an application or form, always download it directly from the web, to ensure you are using the most current version.
If you have any questions about any of the information above, please feel free to contact me at jmatuk@notes.cc.sunysb.edu , phone 632-9036.