October 21, 2011 -
A good summary of the proposed changes to the common rule for human subject protection.
Reforming the Regulations Governing Research with Human Subjects
E.J. Emanuel and J. Menikoff
The federal policy regulating research with human subjects, known as the Common Rule, has not been modified since its publication in 1991. A working group convened by the OMB has drafted a proposal to revise the Common Rule and seeks public comment.
September 11, 2011 -
On September 7, 2011, the Office for Human Research Protections (OHRP) and the Food and Drug Administration announced in the Federal Register the availability of a joint draft guidance document entitled, “Guidance on Exculpatory Language in Informed Consent,” and are inviting public comments on that document. The joint draft document, among other things, does the following:
1. Provides guidance on the regulatory prohibition on the inclusion of exculpatory language in informed consent.
2. Includes examples of language that OHRP and FDA consider acceptable as well as examples of language that the agencies would consider exculpatory.
3. Clarifies that OHRP and FDA have concluded that language in informed consent is not exculpatory if it informs subjects that, by agreeing to allow the use of their biospecimens for research purposes, they are giving up any legal right to be compensated for the use of the biospecimens. This represents a change from OHRP’s November 15, 1996 guidance on point, “‘Exculpatory Language’ in Informed Consent, ” which identified as “exculpatory” certain informed consent statements in which subjects gave up any rights they might have in their biospecimens.
OHRP and FDA now consider these statements to be acceptable for inclusion in informed consent, and they are restated as examples of acceptable language in the draft guidance. Thus, for example, it would now be acceptable to include language in a consent form such as ‘I give up any property rights I may have’ in biospecimens, or ‘I voluntarily and freely donate’ the biospecimens to a particular institution.
When finalized, the draft document will supersede OHRP’s November 15, 1996, guidance entitled, “‘Exculpatory Language’ in Informed Consent” and question number 52 in FDA’s January 1998 guidance entitled, “Institutional Review Boards Frequently Asked Questions – Information Sheet Guidance for Institutional Review Boards and Clinical Investigators.”
The Federal Register notice of availability, the joint draft guidance document, and instructions for how to submit comments can be accessed on the OHRP website at http://www.hhs.gov/ohrp/newsroom/rfc/. The joint draft guidance document can also be accessed on the FDA website at http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/ProposedRegulationsandDraftGuidances/default.htm
June 13, 2011 -
New Pathology Testing Device Enables Oncologists to Diagnose Cancer in One Hour at the Bedside with 96% Accuracy
June 13, 2011
Smartphone-based lab testing device could eliminate need to send biopsies to pathology laboratories
For years, pathologists have wondered when technology would make it feasible to diagnose cancer at the patient’s beside. Eliminating the need for a traditional biopsy that goes off to the anatomic pathology laboratory, and requires 24 hours or more to process the tissue and evaluate the case. Now scientists at Harvard Medical School may be close to perfecting a device that can allow oncologists to do exactly that type of bedside analysis and produce a diagnosis in 60 minutes or less!
The heart of this technology is a new microchip that interacts with smartphone software. Researchers believe it will be possible for physicians to diagnose cancer at the bedside in less than 60 minutes.
Engineered by scientists at Harvard Medical School and Massachusetts General Hospital, the portable nuclear magnetic resonance (micro-NMR) system analyzes small tissue samples. This system accurately identifies malignancies 96% of the time, which, according to the researchers, is more accurate than the existing cancer tests used by pathology laboratories and clinical laboratories.
In a study published in Science Translational Medicine, researchers took the wraps off their quantitative micro-NMR system. They claim that it “shows potential for cancer diagnosis in the clinic” and at the point of care.
Micro-NMR Technology Removes Human Error in Pathology Testing
Hakho Lee , Ph.D., is one of the study’s authors. He is also an Assistant Professor at the Center for Systems Biology at Massachusetts General Hospital. In an article published in Technology Review, Lee suggested that removing the possibility for human error might explain the micro-NMR test’s extreme accuracy.
As described by Lee, the standard procedure now in use requires a physician to send a patient’s tissue biopsy to a lab. There the tissue is processed in the histology laboratory, then mounted on slides and analyzed by surgical pathologists. However, Lee noted that this workflow can introduce proteins not present in the original tissue sample. By contrast, the new micro-NMR test bypasses that entire anatomic laboratory process.
“In our design, we inject everything from the patient into the device, and then it will give out a result,” said Lee in the Technology Review article.
According to the final report by the study authors, “The mean clinical turnaround time for conventional pathology, from sample submission to final report, was three days for cytology (range, one to eight days) and four days for surgical pathology (range, one to 11 days). The measurement time for [micro-NMR] was typically less than 60 minutes.
“Conventional cytology on fine-needle aspirate specimens was performed in 49 of 50 cases, and provided an accurate diagnosis in 36 of 49 cases (accuracy, 74%). Conventional histology was done on all core biopsies and correctly diagnosed 45 cases (accuracy, 84%). The remaining results either were non-diagnostic (five cases), or provided a false-negative result (eight cases). Thus, [micro-NMR] performed consistently better (accuracy, 96%) than the current standard of care.”
Nanotechnology Key Element in Micro-NMR Laboratory Testing System
The micro-NMR system can simultaneously detect proteins from multiple types of cancers. To do this, researchers developed a microchip that holds magnetic nanoparticles in a solution. Binding molecules, or ligands, are then attached to the nanoparticles. When tissue samples from patients are injected into the microchip, the system generates a magnetic field through which the smartphone-based software identifies which proteins have attached to which ligands. This enables the device to then deliver a positive or negative result for specific cancer types.
Researches discovered, however, that the proteins degraded quickly after about an hour, leading them to conclude that for the test to be successful, the sample proteins would have to be fixed on the cell surface, or the test would have to be concluded within the one-hour window. The researchers opted for the latter. They designed the micro-NMR chip to install on a smartphone, enabling physicians to analyze the sample and render a diagnosis at the patient’s bedside in less than 60 minutes.
“People would like to do protein-based diagnostics via blood analysis,” said James Heath, Ph.D., Professor of Chemistry at California Institute of Technology in the same Technology Review article. “For either blood or tissue analysis, sample degradation over time is a common issue. [The micro-NMR] certainly overcomes the challenge ... since the measurements are all done very quickly following biopsy.”
Micro-NMR’s first application will be used to diagnose tuberculosis. The research group’s next project involves using the system to detect ovarian cancer.
Of course, it will take some time before this micro-NMR technology makes it through regulatory approval and is ready for use in clinical settings. However, for pathologists and clinical laboratory managers, this is an example of how several disparate technologies can be brought together to create a sophisticated molecular diagnostic test that has the potential to be highly-disruptive to long-standing work practices in surgical pathology.
The Associated Press State & Local Wire
Federal rules: No genetic screening for jobs
By TIM DORAN, The Bulletin
Federal regulations making it illegal for employers to discriminate against workers or job applicants based on their genetic information became effective Monday.
The rules should be familiar to Oregon employers the state has prohibited use of genetic screening in employment since the mid-1990s, according to state records.
Still the U.S. Equal Employment Opportunity Commission created more detailed regulations for the federal law, said Miranda Grier, who teaches employment law at the University of Oregon School of Law.
"I think it's an additional protection," she said.
As part of the Genetic Information Nondiscrimination Act of 2008, employers also cannot request, require or purchase genetic information, and the law strictly limits its disclosure, according to the Oregon Bureau of Labor and Industries and the EEOC.
Congress passed the legislation, which also deals with potential discrimination in health insurance coverage, in 2008. The EEOC adopted rules for the employment portion in November, and they became effective Monday.
Genetic research has advanced quickly over the past 20 years. Scientists mapped out the human genome, which equals all the genes that make up humans, in 2003.
The advances, which prompted the law, make it possible for people to learn their potential to develop certain medical conditions based on their family histories, according to a recent BOLI technical assistance column.
Treatment for some conditions can be costly, so concerns cropped up about the potential misuse of genetic information by insurance companies and employers, many of which pay for their employees' health insurance, Grier said.
For example, she said, to keep costs down, an employer may decide not to hire employees if they or their family members have the potential for certain medical conditions.
"Employment should be related to a person's performance on the job," Grier said.
While genetic employment discrimination has not generated a large number of lawsuits, Grier said, it's a concern, especially as the public becomes more aware of genetic research.
These days, she said, many women know if they have a gene that indicates they are more likely to develop breast cancer.
The law covers businesses with 15 or more employees, along with labor unions, employment agencies and apprenticeship and training programs, according to BOLI, and it protects individuals or family members, including fetuses or embryos of those receiving fertility treatments.
The Genetic Information Nondiscrimination Act defines genetic tests as those that reveal, for example, a predisposition to breast cancer, colon cancer, Huntington's disease, or screening for cystic fibrosis or sickle-cell anemia.
Employers may test workers to determine if they have alcohol or illegal drugs in their systems. But they cannot test for employees' genetic predisposition to alcoholism or drug abuse.
The law allows several exceptions when obtaining genetic information would be allowed. They include:
Overhearing the information inadvertently, or in a casual conversation, although probing follow-up questioning would be prohibited.
Employees' participation in voluntary wellness programs, provided employers cannot access the information.
Obtaining medical conditions to verify the need for leave under the Family and Medical Leave Act.
Learning the information from publicly available sources, such as television, the Internet or publications.
Similarly, the law allows exceptions when disclosing genetic information would be allowed. They include:
When it is requested in writing by the employee.
When giving it to a health researcher.
If it's in response to a court order.
Providing it to government officials investigating compliance with the Genetic Information Nondiscrimination Act.
Given Oregon's history in prohibiting employment discrimination based on genetic information, complying with the new federal regulations should not require much more from businesses, Grier said.
"I think that it fits right in with the system employers use in (following) the Americans with Disabilities Act and the Family and Medical Leave Act," she said.
January 2, 2011 - The 2011 edition of the International Compilation of Human Subject Protections has just been released and is now available on-line. The document can be seen at http://www.hhs.gov/ohrp/international/2011-hspcompilation.pdf.
The updated compilation includes a listing of over 1,000 laws, regulations and guidelines on human subject protections in 101 countries and from several international organizations. The new compilation also features the standards regarding device research, which were identified in 44 countries. These laws, regulations and guidelines are classified into six categories:
Drugs and Devices
Human Biological Materials
Embryos, Stem Cells and Cloning
New countries included in this year's edition are Belarus, Grenada, Pakistan, Rwanda and Tunisia. Many of the listings include a hyperlink, allowing the reader to link directly to the law, regulation or guideline of interest.
Prepared by the Office for Human Research Protections of the U.S. Department of Health and Human Services, the compilation is designed for use the IRBs, researchers, sponsors and others involved in human subjects research around the world.
10/16/2010 - In the FWA frequently asked questions (FAQs), at http://www.hhs.gov/ohrp/FWAfaq.html, OHRP has revised the answer to Question #4: When is an institution considered to be "engaged in research"? The revisions include:
Adding obtaining informed consent as an activity that can make an institution engaged;
Removing the statement that pertained to awardee institutions bearing the ultimate responsibility for protecting human subjects, even when all human subjects activities are carried out by other institutions; and
Correcting the link at the end of the FAQ to link to the current guidance document.
This FAQ was revised to be consistent with OHRP's October 16, 2008 guidance document on the Engagement of Institutions in Human Subjects Research. Specifically, consistent with OHRP's 2008 engagement guidance document, the FAQ was modified to clarify that an institution is generally considered to be engaged in human subjects research when its employees or agents obtain the informed consent of human subjects. OHRP also removed the statement in the FAQ that pertained to awardee institutions bearing the ultimate responsibility for protecting subjects involved in the research conducted under the award, even when all human subjects activities are carried out by other institutions. OHRP removed this statement to be consistent with OHRP's 2008 engagement guidance, which reflects OHRP's broader goal of directing communication about noncompliance to the institution or IRB most directly involved in any regulatory noncompliance with 45 CFR part 46 as appropriate. For an example of the application of this concept, see OHRP's recent determination letter at http://www.hhs.gov/ohrp/detrm_letrs/YR10/sep10b.pdf.
The revised FAQ answer is:
When is an institution considered to be "engaged in research"?
In general, an institution is considered to be engaged in human subjects research when its employees or agents:
(1) obtain data about living individuals for research purposes through intervention or interaction with them,
(2) obtain individually identifiable private information for research purposes (45 CFR 46.102(d),(f)) http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm#46.102; or
(3) obtain the informed consent of human subjects.
Employees and agents, including students, are individuals performing institutionally designated activities and acting on behalf of the institution or exercising institutional authority or responsibility.
In general, an institution is considered to be engaged in human subjects research whenever it receives a direct HHS award to support such research, even if all of the human subjects activities will be performed by agents or employees of another institution. In general, simply informing potential subjects about a research study is not considered engagement in research. Also, providing written information about a research study, including how to contact the investigators for information and enrollment, and seeking and obtaining prospective subjects' permission for investigators to contact them are not considered engagement in research. However, seeking or obtaining informed consent from a research participant is considered engagement in research.
[For details, please see OHRP guidance on this topic at; http://www.hhs.gov/ohrp/humansubjects/guidance/engage08.html specifically, Section (B)(4).]
10/05/2010 - Clarification of "Noninvasive" in Expedited Review Category 3: OHRP has posted a new item of correspondence on its view about the meaning of "noninvasive" as the term is used in expedited review category 3, which is the expedited review category that applies to the prospective collection of biological specimens for research purposes by noninvasive means. OHRP's statement can be viewed at http://www.hhs.gov/ohrp/policy/correspond/. Specifically, that statement clarifies that OHRP agrees with the Food and Drug Administration's position that for purposes of expedited review category 3, the following procedures are considered noninvasive:
Vaginal swabs that do not go beyond the cervical os; Rectal swabs that do not go beyond the rectum; and Nasal swabs that do not go beyond the nares.
09/22/2010 - Guidance on Withdrawal of Subjects from Research: OHRP has posted on its website a finalized guidance document entitled, "Guidance on Withdrawal of Subjects from Research: Data Retention and Other Related Issues." The guidance document provides OHRP's first formal guidance on this topic and finalizes the draft guidance entitled, "Guidance on Important Consideration for When Participation of Human Subjects in Research is Discontinued", that was made available for public comment through a notice in the Federal Register on December 1, 2008 (73 FR 72804). The public comments submitted on our draft document were very helpful to us as we finalized this guidance document, and we thank those of you who took the time to provide us with your feedback. The finalized guidance document is available on the OHRP website at
http://www.hhs.gov/ohrp/policy/subjectwithdrawal.html or http://www.hhs.gov/ohrp/policy/subjectwithdrawal.dpf. The Federal Register notice announcing the availability of this new guidance document can be found at http://edocket.access.gpo.gov/2010/2010-23517.htm or http://edocket.access.gpo.gov/2010/pdf/2010-23517.pdf.
Storing Patients' Tumor Tissue for Future Study
The Philadelphia Inquirer, 08/18/2010, By Stacey Burling; Inquirer Staff Writer
GINA Legislation Update, April 6, 2009 - Information for Researchers and Health Care Professionals. For links and information please check the News & Views folder.
ISBER, March 2009 - Newsletter! See details in News & Views folder.
TwinBiobank, http://www.timesonline.co.uk/tol/news/uk/science/article6004963.ece - A database of 300,000 pairs of twins that would be by far the largest in the world is being planned by British scientists to investigate the genetic and environmental origins of disease and behaviour.
BRN symposium: Helen Moore provided the following update:
· The archive of the 2009 BRN Symposium is available on the Symposium website: http://brnsymposium.com/meeting/brnsymposium/2009/
· The agenda and the presentations are posted on the following web page: http://brnsymposium.com/meeting/brnsymposium/2009/agenda.asp
· The archived webcast is posted on the following web page: http://brnsymposium.com/meeting/brnsymposium/2009/webcast-registration.asp
Guidance on the Genetic Information Nondistrimination Act: Implications for Investigators and Institutional Review Boards (Link to DHHS Document).
NCI Best Practices for Biospecimens Resources (2007): [download 48-page document]
The Critical Role of Biospecimens in Cancer Research, an interview with NCI OBBR Director Dr. Carolyn Compton (2008): [download 12-minute interview]
NIH Catalyst article, "Program Expanded for 2009 Biospecimen Symposium" (Jan-Feb 2009): [download entire issue, refer to page14]
"What's Wrong With Summer Stiers?," a New York Times Magazine article about the NIH Undiagnosed Diseases Program, organized by the National Human Genome Research Institute, the NIH Office of Rare Diseases (ORD) and the NIH Clinical Center (February 22,
NCI Office of Biorepositories and Biospecimens Research
NIH Office of Rare Diseases Research