Veit, a frequent industry speaker, and his co-panelists from Duke Medicine, Harvard University and Duke University Health System IRB, will discuss the practical implications and ethical considerations for multisite clinical trials conducted in a global setting during their session titled “Globalization of Clinical Research: Emerging Issues for Sponsors, Academic Research.” The panelists will provide strategies for sponsors, Academic Research Organizations and IRBs to work collaboratively to ensure the quality of global clinical trials.

CGIRB is a key contributor to the symposium. In addition to Veit’s presentation, CGIRB Vice President and Chief Business Development Officer Bill Van Nostrand and Quality Management Director Yvonne Higgins are members of the symposium’s program committee. Higgins will also moderate a panel discussion titled “Certifying Investigators, Accrediting HRPPs & Qualifying Phase I Clinics.”

“Emerging issues in global clinical research is a key topic,” Veit said. “The collaboration between all involved parties needs to be consistent in order to improve efficiencies, obtain the best quality data and ensure the safety of human clinical trial subjects.”

The May 15 symposium will bring together speakers from industry, academia, government as well as researchers from other countries who will focus on the protection of human subjects participating in global clinical trials, streamlining processes and minimizing the challenges of multiregional clinical trials. The program includes speakers representing the U.S. Food and Drug Administration, Copernicus Group IRB, Sanofi, Yale University, Harvard Medical School, Duke University Medical Center and Celgene.

For more information about the symposium and to register, please click here.

About Copernicus Group IRB
Experience and innovation in ethical review®
Copernicus Group IRB, established in July 1996, is a leading U.S. independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010. For more information please visit http://www.cgirb.com

About the Drug Information Association
The Drug information Association (DIA) is a neutral, global, professional, member-driven association of nearly 18,000 professionals involved in the discovery, development, and life cycle management of pharmaceuticals, biotechnology, medical devices and related medical products. Through international educational offerings and myriad networking opportunities, DIA provides a global forum for knowledge exchange that fosters the innovation of products, technologies and services to improve health and wellbeing worldwide. Headquarters are in Horsham, Pa., USA, with offices in Basel, Switzerland, Tokyo, Japan, Mumbai, India and Beijing, China. www.diahome.org.

About Duke Clinical Research Institute
The Duke Clinical Research Institute (DCRI), the world’s largest academic clinical research organization, is known for conducting groundbreaking multinational clinical trials, managing major national patient registries, and performing landmark outcomes research. DCRI research spans multiple disciplines, from pediatrics to geriatrics, primary care to subspecialty medicine, and genomics to proteomics. The DCRI also is home to the Duke Databank for Cardiovascular Diseases, the largest and oldest institutional cardiovascular database in the world, which continues to inform clinical decision-making 40 years after its founding. www.dcri.org

CGIRB Vice President and Chief Business Development Officer Bill Van Nostrand and Quality Management Director Yvonne Higgins are collaborating with fellow committee members to create a program aimed at addressing the challenges involved in conducting global clinical trials including levels of protection and the diversity of regulations, requirements, and ethical issues that are unique to the conduct of clinical trials in a global setting at the “Creating a Global Clinical Trial Platform: Partnering for Synergy” symposium in Durham, N.C.

The May 15 symposium will bring together speakers from industry, academia, government as well as researchers from other countries who will focus on the protection of human subjects participating in global clinical trials, streamlining processes and minimizing the challenges of multiregional clinical trials. The program includes speakers representing the U.S. Food and Drug Administration, Copernicus Group IRB, Sanofi, Yale University, Harvard Medical School, Duke University Medical Center and Celgene.

“Our goal in organizing this program is to provide a forum for sharing and encouraging best standards in the ethical conduct of global clinical trials,” Higgins said. “The group of speakers and the agenda the program committee has assembled is impressive.”

Panelists will share their perspectives on ethical and resource responsibilities in a global setting, the state of clinical research, how to conduct simultaneous global studies, certifying investigators, accrediting HRPPs and qualifying phase I clinics, globalization of clinical research and emerging issues for sponsors, academic research organizations & IRBs.

“At CGIRB, we always look for ways to partner and create innovative ways to improve efficiencies and consistency in human subject research protection,” Van Nostrand said. “We hope to inspire attendees with solutions for enhancing the conduct of multiregional clinical trials.”

For more information about the symposium and to register, please click here.

About Copernicus Group IRB

Experience and innovation in ethical review®

Copernicus Group IRB, established in July 1996, is a leading U.S. independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010.

Federal regulations for the protection of human subjects assign the principal investigator with the ultimate responsibility for ensuring the safety, rights and welfare of research subjects. Chief among those responsibilities is the obligation to ensure that the regulatory and ethical requirements relating to obtaining informed consent are met.

Investigators are sometimes confronted with different situations regarding the need for other persons to be part of the informed consent process. This may necessitate additional signature lines on the Informed Consent Document (ICD), in addition to the one containing the subject’s name. One situation frequently encountered is the addition of “Impartial Witness” signature lines.

Use of an Impartial Witness is necessary when either the subject or the subject’s legally authorized representative (LAR) speaks and understands English, but cannot read and write or is visually impaired. Persons who cannot read and write are considered illiterate. Visual impairments include blindness and other visual defects in which changes to the consent document, such as increased font size, are insufficient to allow the subject (or LAR) to read it. It is important to emphasize that use of an Impartial Witness is limited to situations in which the subject (or the subject’s LAR) comprehends spoken English and is able to communicate.

What is an Impartial Witness?

ICH Good Clinical Practice (GCP) defines an Impartial Witness as “a person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.” This definition contains four parts, all of which must be met. Here they are presented separately for emphasis and analysis:

• “Who is independent of the trial:” This could be a person who is a family member. It would not be a member of the site staff involved with the study.
• “Who cannot be unfairly influenced by people involved with the trial:” This would be a person free from potential coercion or undue influence or conflicted interest.
• “Who attends the informed consent process if the subject or the subject’s legally acceptable representative cannot read:” This emphasizes the participation of the witness throughout the consent process, not just when the subject signs. A robust informed consent process will likely result, on the part of the person obtaining consent.
• “Who reads the informed consent form and any other written information supplied to the subject:” This responsibility has the witness confirming the subject was presented sufficient information to assure truly informed consent of the subject.

Why the Impartial Witness signature?

The purpose of the Impartial Witness signature is to attest to the fulfillment of the regulatory requirements as stated in 21 CFR 50.20 – General requirements for informed consent. This includes affirming that the prospective subject was provided sufficient opportunity to consider whether or not to participate, that the possibility of coercion or undue influence was minimized, and that the information given to the subject was in language understandable to the subject or the representative. The witness can further attest that the informed consent, whether oral or written, did not include any exculpatory language through which the subject was made to waive or appear to waive any of his/her legal rights, or release or appear to release the investigator, the sponsor, the institution, or its agents from liability for negligence.

ICH GCP further adds: “By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the subject or the subject’s legally acceptable representative, and that informed consent was freely given by the subject or the subject’s legally acceptable representative.

The Impartial Witness should sign and personally date the consent form after all of the following occur:

• The written informed consent document and any other written information  provided to subjects is read and explained to the subject (or the subject’s LAR)

• The subject (or the subject’s LAR) has orally consented to the subject’s participation in the trial
• And, when capable of doing so, the subject (or the subject’s LAR) has signed (or made his/her “mark”) and personally dated the informed consent form (when capable).

Cases of physical compromise

According to the FDA information sheets, the use of an Impartial Witness may also be required when a potential subject is physically compromised.

If the subject or LAR can read and write, an Impartial Witness does not need to be part of the consent process unless there is state law requiring an Impartial Witness, or if a site’s and/or institution’s Standard Operating Procedures (SOP) require this addition to the consent process and ICD.

Pre-determined policy recommended

Having a pre-determined written definition or policy of who may serve as an Impartial Witness is recommended as a useful SOP for all sites that conduct informed consent on a regular basis as a way to ensure regulatory compliance. This allows for potential witnesses to be educated in this role, and will help minimize hasty choices or study-related site personnel being pulled in unprepared, or inappropriately, to serve as an Impartial Witness.

The IRB may guide this choice, but it is good practice for the site to be able to identify and define who can serve in this Impartial Witness role within its walls. Staff involved with the study should not serve as Impartial Witnesses. This, by extension, leaves non-study staff (“employees of the institution who are not engaged in the conduct of the research”) and “relatives” to serve as Impartial Witnesses. The decision to choose a family member or non-study staff member can be flexible or situational. For example, if a potential subject arrives without a family member but requires an Impartial Witness, the burden on a subject to return with a family member is negated by ability of a non-study staff member serve as the Impartial Witness.

Impact on short-form written ICDs

Finally, though infrequently utilized in the routine clinical study setting, it is important to note the mandated use of an Impartial Witness when the IRB authorizes the use of a “short-form written ICD.” Here is the second of the two descriptions of the “written consent document” presented under “Documentation of informed consent,” in the regulations at  § 46.117 and §  50.27.

(2) A short form written consent document stating that the elements of informed consent required by § 46.116  //  § 50.25 have been presented orally to the subject or the subject’s legally authorized representative. When this method is used, there shall be a witness to the oral presentation. Also, the IRB shall approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the summary, and the person actually obtaining the consent shall sign a copy of the summary. A copy of the summary shall be given to the subject or the representative in addition to a copy of the short form.

In this description, “witness to the oral presentation” reinforces the concept of the participation of the witness throughout the consent process, not just when the subject signs. In the circumstances where use of the short form is appropriate, the witness can also bring a further element of impartiality to the decisions.

Placement of the Impartial Witness signature line

It is effective to place the Impartial Witness’ signature lines after the subject’s line(s), and after the lines of the person obtaining consent. When the study allows subjects for whom an Impartial Witness may be necessary, having the Impartial Witness lines qualified as “if applicable” presents these lines consistently across all consent forms, avoids the need for an updated ICD and mitigates the temptation to make unapproved modifications to the ICD.

When an Impartial Witness is required, he/she plays a key role in the informed consent process. Proactively identifying who can serve in that role can help ensure a smooth consent process, with maximal return and minimal obstacles. Since correctly documented signatures are part of an appropriate consent process, the investigator has the responsibility to follow the regulations and to ensure that documentation is correctly managed.

Ms. Higgins’ presentation, “Building a Quality Institutional Review Board/Ethics Review Committee,” included discussions of the attributes of a quality IRB, review tools and strategies, and case studies on the use of quality management principles in an IRB context.

APREC is a premier Asia Pacific platform focusing on human subject protection, committed to bringing together the region’s institutional review boards, ethics committees, research and academic institutions and health authorities, as well as representatives from the pharmaceutical industry. Speakers hailed from regions around the world, including the U.S., Japan, Australia and Malaysia.   Conference faculty from the U.S. included Ezekiel Emanuel, Nick Slack, and Elisa Hurley.

“The globalization of the development and delivery of health care solutions provides a unique opportunity for us to share innovative approaches on enhancing research ethics, ensuring respect for study subjects, and protecting subject safety,” Higgins said. “This conference brought together key stakeholders in the clinical trials process, including sponsors, government officials, researchers, IRBs, and clinical research organizations. Many of those people may not normally attend the same conference, but everyone was engaged and energetic about looking for best practices in the field of human research subject protection.”

About Copernicus Group IRB
Experience and innovation in ethical review®

Copernicus Group IRB, established in July 1996, is a leading U.S. independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010.

Connexus, CGIRB’s award-winning e-document management system, is utilized by sponsors, CROs and sites to manage every phase of the IRB review process. Connexus 2.0 is a complete upgrade to the system’s look and feel, offering a cleaner, faster and more intuitive experience, while still giving users the ability to track submissions, access an electronic file cabinet of all IRB documents and receive instant notification when a submission is complete.

“When it was originally released, Connexus created a major shift in the IRB industry,” said Jennifer Sodrel, CGIRB’s Director, Information Management. “Being a company focused on quality and innovation, we constantly look for ways to improve and enhance our systems. Our goal with the 2.0 release was to make Connexus an even more valuable tool for our clients.

“With Connexus 2.0, we’ve updated the look of the user interface, as well as reworking elements to make it simpler to use and more intuitive. We took care to make sure users of the original Connexus will be able to transition to the new version very easily.”

New features in Connexus 2.0 include:

• Cleaner inboxes for workspace managers.
•  Instant access to live chat with CGIRB support personnel
• Links to CGIRB news on the Connexus login screen, for the latest information

For information on how to register for Connexus or Connexus training, please visit http://www.cgirb.com/cgirb-connexus/

About Copernicus Group IRB
Experience and innovation in ethical review^®

Copernicus Group IRB, established in July 1996, is a leading U.S. independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010.

Sydney Douglas, CGIRB’s corporate trainer, accepted the award at Training’s 2012 Conference and Expo, held Feb. 13-15 in Atlanta. CGIRB, the only IRB to be recognized, was among the 24 new companies that broke the Top 125 list this year and one of only three companies on the list with less than 100 employees.  Over 600 people attended the award ceremony, many representing other winners, including powerhouse brands such as ADP, Intel Corp., UPS and Verizon.

Douglas manages the training program which includes new employee orientation, skill development, interdepartmental training, accreditation/certification programs and coordination of corporate training initiatives. CGIRB’s training-focused environment enables new employees to quickly acclimate and contribute to the corporate culture, while ensuring seasoned staffers remain at the forefront of the industry.

The Training Top 125 award recipients were organizations that excelled at employee development in 2011 and was based on multiple benchmarking statistics, such as total training budget,  hours of training per employee, content of training initiatives and assimilation of corporate goals, evaluation and metrics, workplace surveys, and detailed formal programs.

“This award validates our training-focused approach at CGIRB,” Douglas said. “By making ongoing training and certification efforts a top priority, we keep our staff and our methodologies on the cutting edge. The awards ceremony was an amazing event and I was so honored to represent CGIRB. Training is such an important and integrated part of how we operate, so we are extremely excited and proud to be recognized for our work and to be named one of Training’s Top 125 companies.”

About Copernicus Group IRB
Experience and innovation in ethical review^®

Copernicus Group IRB, established in July 1996, is a leading U.S. independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010.

About Training magazine

Based in Minnesota, Training magazine is a 48-year-old professional development magazine that advocates training and workforce development as a business tool. Training is published by The Lakewood Media Group.

The CGIRB Associate Project Manager spoke to undergraduates at the Buies Creek, N.C., school about Informed Consent. Schepker’s lecture featured information on the history of institutional review boards, the Tuskegee study, IRB formation and makeup, elements of Informed Consent and CGIRB’s internship program.

Students also participated in a group activity, reviewing and identifying elements of Informed Consent on a working Informed Consent Form.

Veit taught a three-hour class in Vulnerable Populations to graduate students in Campbell’s Clinical Research program. It was the third year Veit was invited to present at the Buies Creek, N.C., school.

Higgins will present on Quality Management and Quality Improvement in Research – one of the featured tracks of the March 7-9 conference at the Grand Copthorne Waterfront Hotel. Other speakers in Higgins’ track include HRP Consulting Group Consulting Services Director Nicholas C. Slack and Johnson & Johnson Quality and Compliance Lead Regional Director Angie Sim.

APREC is a premier Asia Pacific platform focusing on human subject protection. APREC is committed to bringing together the region’s institutional review boards, ethics committees, research and academic institutions and health authorities, as well as representatives from the pharmaceutical industry.

The Food and Drug Administration this year published revised regulations pertaining to safety reporting for drug and biologic products under an Investigational New Drug (IND) application. The FDA also made bioavailability (BA) and bioequivalence (BE) studies conducted to support the approval of a generic drug subject to IND safety reporting requirements.

Let’s look at how these changes in 21 CFR 312 will impact IND safety reporting.

Why revise?

The FDA appears intent on reducing the number of IND safety reports that are uninterpretable or do not contribute to a better understanding of the developing safety profile of the drug or biologic. In the guidance that accompanies the new regulations, the FDA seems to acknowledge there are too many reports for adverse events in which there is little evidence of a causal relationship between the drug and the adverse event. In fact, the default position for both sponsors and investigators has been “over-reporting” safety events.

The FDA also appears intent on clearing up confusion over the term “adverse drug experience.” Under prior IND regulations (21 CFR § 312.32), there was little guidance about which “adverse drug experiences” during clinical trials required reporting, resulting in sponsors often reporting all serious adverse events, even when there was little reason to believe they were associated with the investigational drug.

As a result, the new regulations eliminate the term “adverse drug experience” and replace it with two terms: “adverse event” and “adverse reaction.” An “adverse event” is, simply, any adverse event observed during a clinical trial. An “adverse reaction” is an adverse event in which there is reason to conclude the drug caused the event.

What gets reported?

The FDA now requires sponsors to file IND safety reports for suspected adverse reactions that are both serious and unexpected. There must now be a “reasonable possibility” the drug caused the adverse event – that is, there must be evidence to suggest a causal relationship.

The FDA provides three examples of when such a “reasonable possibility” of causality may be drawn, requiring an IND safety report:

• When the event is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome)
• When the event is not commonly associated with drug exposure, but is uncommon in the population exposed to the investigational drug (e.g., tendon rupture)
• When an aggregate analysis of specific events indicates the events occur more frequently in the drug treatment group than in controls

In addition, the guidance document makes it clear the FDA expects such information be based on unblinded analysis of the events, as information on what treatment the patient received could “provide critical safety information about the drug that could have implications for the ongoing conduct of the trial.”

What else must sponsors report?

In addition to serious and unexpected suspected adverse reactions, the new regulations require the sponsor to submit IND safety reports to the FDA and all investigators about:

• Findings from other studies
• Findings from animal or in-vitro testing
• An increased rate of occurrence of serious suspected adverse reactions

Findings from other studies

IND safety reports must be submitted when findings “suggest a significant risk in humans exposed to the drug” in other studies. These may include epidemiological studies, analyses of multiple studies and clinical studies other than those conducted under the present IND. They can also include studies not conducted under an IND or by the sponsor of the present IND.

Information that requires reporting would typically be that which would lead to safety-related changes in the protocol, informed consent document, investigator brochure or other aspects of the clinical investigation.

Findings from animal and in-vitro testing

The new FDA rule requires sponsors to submit an IND safety report if animal or in-vitro testing suggests a significant risk to humans exposed to the drug. This would include reports of mutagenicity, teratogenicity, carcinogenicity or organ toxicity.

Findings requiring reporting would typically be those which lead to safety-related changes in the protocol, informed consent, investigator brochure or other aspects of the clinical investigation.

Increased rates of occurrence of serious suspected adverse reactions

Sponsors are also required to file an IND safety report when they discover “any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.” This requirement was added for consistency with ICH guidance and the FDA’s expectation that the sponsor track and identify changes in rates of adverse events during the conduct of a clinical trial.

In addition, there is a requirement to report serious suspected adverse reactions that are anticipated within the drug class but not specifically mentioned as occurring with the particular drug under investigation. Under this rule, a serious adverse reaction known to occur in the class of drugs, but not yet observed in the drug under study, would be considered “unexpected” – and therefore reportable the first time it occurs in the study drug.

The final rule also adds the requirement that sponsors report serious and unexpected suspected adverse reactions even if the event may be considered a component of a study endpoint. For example, death from anaphylaxis must be reported, even if a study endpoint is all-cause mortality, when death from anaphylaxis is unexpected and if there is a reasonable possibility that the drug caused the anaphylaxis. Serious and expected suspected adverse reactions that are study endpoints need not be reported as IND safety reports, and should only be reported as described in the study protocol.

What must investigators report?

Under the FDA’s revised reporting requirements in 21 CFR § 312.64 (b), investigators must immediately report to the sponsor any serious adverse event, whether it is considered related to the drug or not – including events listed as “known to occur” in the protocol or the investigator’s brochure.

The investigator must include an assessment as to whether there is a “reasonable possibility” that the drug caused the event. Study endpoints that are also serious adverse events should be reported in accordance with the study protocol unless there is evidence suggesting the event was caused by the study drug. These requirements are in addition to other protocol-specific requirements for safety reporting.

The takeaway

The new regulations are a good start on addressing the problem of over-reporting of IND safety reports under the previous regulatory scheme. But whether the new regulations will result in decreasing the number of individual IND safety reports remains to be seen.

In addition, sponsors and investigators will be dealing with new expectations pertaining to analysis of adverse events and will need to develop new processes to determine the significance of adverse events in clinical trials. We may see the role of Data Monitoring Committees (DMC) expanded for the purpose of analyzing and evaluating un-blinded data to determine whether the events must be reported.

As with any overhaul of regulations, the true effect of the changes is yet to be shown.

CGIRB Chairperson Glenn Veit, JD, CIP, spoke on “Sponsor Responsibilities in Unanticipated Problems and Adverse Event Reporting.” His presentation reviewed new FDA regulations on adverse event reporting in Investigational New Drug (IND) trials, which went into effect in March.

CGIRB Quality Management Director Yvonne Higgins, CIP, spoke on IRB operations and management, as well as research team oversight and education. She also participated in an open discussion with other HRPP and IRB experts, and served as co-chairperson for the conference’s workshop and didactic subcommittee.

The conference was presented by Public Responsibility in Medicine and Research (PRIM&R), an organization dedicated to advancing the highest ethical standards in the conduct of research.

Dec. 6, 2011, Research Triangle Park, N.C. – Copernicus Group IRB (CGIRB), a leading independent institutional review board, has been named a finalist in Training Magazine’s annual Top 125, which ranks companies’ excellence in employer-sponsored training and development programs.

The final rankings will be announced during Training’s 2012 Conference and Expo, scheduled for Feb. 13-15 in Atlanta.

Training determines its Top 125 rankings using benchmark statistics and by evaluating corporate commitment, formal training programs, program efficacy and innovation. In addition to Copernicus Group IRB, the 2012 finalists include such powerhouse brands as ADP, Intel Corp., UPS and Verizon.

“CGIRB is honored to be the only IRB named as a finalist for the Training Top 125,” Copernicus Group IRB president and CEO Bruce Tomason said. “Our ongoing commitment to the protection of human research subjects demands we maintain the highest training standards. Better staff education leads to increased employee competence, overall experience levels and, ultimately, improved service and impeccable quality for our clients.”

Copernicus Group IRB ’s corporate trainer, Sydney Douglas, manages a training program which includes new employee orientation, skill development, interdepartmental trainings, accreditation/certification programs and coordination of corporate training initiatives.

The resulting training-focused environment enables new employees to quickly acclimate and contribute to the corporate culture, while ensuring seasoned staffers remain at the forefront of the industry.

“This award validates our approach to training at CGIRB,” Douglas said. “By making ongoing training and certification efforts a top priority, we keep ourselves and our work on the cutting edge. At CGIRB, we fully realize the impact of training – that the quality of service we provide to our clients is directly related to the quality of employee training we provide for our staff. Training has always been a part of our culture, and we are thrilled to receive this honor.”

About Copernicus Group IRB
Experience and innovation in ethical review ®
Copernicus Group IRB, established in July 1996, is a leading U.S. independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010.

About Training magazine
Based in Minnesota, Training magazine is a 48-year-old professional development magazine that advocates training and workforce development as a business tool. Training is published by The Lakewood Media Group.

Corporate Contact: Rebecca Sipes, CGIRB rsipes@cgirb.com

Media Contact: Gwen Hoover, Altitude Marketing gwen@altitudemarketing.com

Sawyer’s lecture  included a general overview of the IRB process, with a focus on Human Subject Protection history and the IRB role in the research process. As an example of the IRB review process, Sawyer provided students with information on IRB ad requirements. The talk also included an activity in which students practiced creating an ad for IRB approval.

In the session, entitled “Building Quality IRBs,” Higgins discussed methods of improving human research protection programs by outlining attributes of a quality HRPP, strategies for gaining institutional support, providing guidance and support to the research community, optimizing resources, streamlining reporting requirements and developing a quality improvement program. Additionally, she shared a case study on how one institution brought about improvement of its human research protections program.

November 1, 2011, Research Triangle Park, NC — Copernicus Group IRB (CGIRB), a leading independent institutional review board, today announced it has been named a finalist in the 2011 North Carolina Technology Association (NCTA) 21 Awards. CGIRB was selected in the “Leading Environmental Steward Company Award” category.

The NCTA 21 Awards are recognized as North Carolina’s most prestigious technology awards, celebrating innovation and excellence in the state. This annual showcase honors companies and individuals in 21 categories who represent the best and brightest in technology and business.

The Leading Environmental Steward Company Award honors the company that best implements a sustainable plan to be more environmentally conscious and socially responsible.

“As an organization focused on quality and innovation, CGIRB is honored to be named as a finalist in the Environmental Steward Company category,” said Bruce Tomason, president and CEO of Copernicus Group IRB. “We are proud to have our paperless e-document management system, CGIRB Connexus®, recognized for its environmental benefits. The system’s advanced functionality makes a truly paperless work environment possible.”

Connexus has altered the landscape and expectations for everyone involved in the IRB review process. Before Connexus, the clinical trial review process was paper-intensive. CGIRB was generating approximately 2,860,000 new pages a year, many of which had to be stored for 10 years or more and accessed repeatedly.

The transformation to a paperless organization allows CGIRB to perform more thorough, efficient reviews by providing secure access to all electronic documentation for current, pending and past studies. In addition, CGIRB dramatically reduced internal and client expenses and created a greener work environment by eliminating paper, printing, storage, shipping and document handling. By combining the inherent advantages Connexus technology with CGIRB’s traditional commitment to personal attention, the result was a new level of excellence in the client experience.

Winners will be recognized at the NCTA 21 Awards Gala on Thursday, November 10, 2011 in Durham, North Carolina.

About NCTA
The North Carolina Technology Association’s mission is “Making North Carolina #1 in Technology and Technology #1 in North Carolina.” The organization does this through three main focus areas: executive engagement, public affairs and enabling member transition to a technology-enabled workforce. For more information, visit http://www.nctechnology.org.

About Copernicus Group IRB
Experience and innovation in ethical review ®

Copernicus Group IRB, established in July 1996, is a leading US independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010.

About CGIRB Connexus®
CGIRB Connexus® is the most advanced integrated paperless document management web portal technology serving the institutional review board (IRB) services industry. Connexus streamlines and enhances the way sponsors, CROs and investigative sites conduct the IRB submission and review process. For more information, visit http://www.cgirb.com/cgirb-connexus/.

Corporate Contact: Rebecca Sipes, CGIRB rsipes@cgirb.com
Media Contact: Gwen Hoover, Altitude Marketing gwen@altitudemarketing.com

October 12, 2011, Research Triangle Park, NC – Copernicus Group IRB will be leading a webinar on Tuesday October 18, 2011. This is a free educational webinar entitled, “Reducing the Barriers to the Conduct and Oversight of Clinical Trials: A Case Study.”

The webinar will discuss the recent announcement of the proposed revisions to existing federal regulations governing human research subjects by the US Department of Health and Human Services (HHS).

The speakers for this presentation will be Barry Mangum, Pharm.D., FCP, Director Clinical Pharmacology, Duke Clinical Research Unit and Yvonne Higgins, A.B., CIP, Director Quality Management at Copernicus Group IRB.

The webinar will provide methods for reducing the barriers to the conduct and oversight of clinical trials. A case study of the collaborative relationship between the Duke University and Copernicus Group IRB in the review and conduct of clinical trials will be presented.

Barry Mangum will present an academic institution’s perspectives of the IRB Process in. Dr. Mangum will describe key barriers and solutions for success in an academic model.

Yvonne Higgins will describe some of the perceived barriers and real solutions the use of independent IRBs as an alternative to the traditional institutional review board model.

The free webinar will be held Tuesday, October 18, 2011 at 11am EDT. Click here to learn more or to register.

About Copernicus Group IRB
Experience and innovation in ethical review ®

Copernicus Group IRB, established in July 1996, is a leading US independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010.

About Duke Clinical Research Unit

The Duke Clinical Research Unit is a state-of-the-art research facility located within the Duke University Medical Center campus that provides infrastructure support to sponsors and investigators who are testing new drug candidates and other cutting-edge therapies and seeking to identify and validate novel biomarkers.

Building on the strength of Duke’s thought leadership, therapeutic expertise, patient base, and access to the latest technologies, the DCRU is a critical component of the Duke Translational Medicine Institute’s efforts to speedily translate new laboratory discoveries into treatments for patients. For more information, please click here.

Date: October 18, 2011    Time: 11 am EST

In a recent announcement of the proposed revisions to existing federal regulations governing human research subjects, the US Department of Health and Human Services (HHS) acknowledged, “There is very little evidence that having multiple IRBs review the same study is increasing protections to subjects,” according to an HHS publication on the recent proposed changes to the review and conduct of human. “By diffusing responsibility for that review, it might actually be leading to weakened protections.”

Click here for more information and to register.

Goals

The goals of this presentation are to provide clarity on the rationale for this proposed change to the federal regulations; to discuss the potential impact on sponsors, CROs, and academic institutions; to dispel some of the myths regarding the independent review board model and to provide a case study of the collaborative relationship between the Duke University and Copernicus Group IRB in the review and conduct of clinical trials.

Background
On July 22, 2011, the U.S. Department of Health and Human Services (HHS) announced a proposal that may result in significant changes to federal regulations on the protection of human research subjects. In the notice, published in the federal register, HHS acknowledged that “the landscape of research activities has changed dramatically” and that there are “many questions about whether the current regulatory framework is adequate and appropriate for the protection of human subjects in the 21st century.” A key purpose of the proposed change is to “…better focus oversight resources on higher-risk research studies.” ¹

The Rulemaking Process

The rulemaking process involves two phases: an advanced notice of proposed rulemaking (ANPRM) followed by a notice of proposed rulemaking. Each phase requires an extended public comment period and subsequent analysis by the government of the comments before publication of the final rule.

The rulemaking process is outlined as follows:

This process presents an invaluable opportunity for IRBs, academic institutions, CROs, pharmaceutical and medical device companies and other stakeholders to provide HHS with initial comments on the proposed changes. Commenters are invited to provide general feedback or to respond to any of the 74 specific questions raised by the authors of the advanced notice.

Key features of the proposed rule
Single IRB of Record for Multi-site US trials
One proposed requirement would be for a single IRB of record for all of the U.S. sites in a multi-site study. This would replace the current practice of multiple and redundant IRB reviews at participating sites.

This proposed streamlined approval process addresses a concern of sponsors and investigators – that a delay in IRB approvals mean delays in the impact of research findings. The ANRPM also suggests that duplicative IRB reviews of multi-site studies not only increases burden, but may also result in weakened protections. Thus, the ANRPM proposes the requirement for a single IRB of record for multi-site studies.

In the discussion of possible solutions, the ANPRM describes two current alternative models of IRB review: the use of central government run IRBs (specifically, the Veterans Affairs CIRB and the National Cancer Institute’s CIRB) and the use of academic consortia. The advanced notice does not acknowledge the existence or merit of other alternative models of IRB review such as review of industry sponsored research by independent IRBs.

Calibrating IRB review based on research risk
A series of changes to the review of research that poses no more than minimal risks to research participants including:

• Expanding the list of research categories eligible for expedited review
• Eliminating the requirement for continuing review of minimal risk studies
• Expanding the categories of research currently reviewed as exempt

Enhancing Informed Consent
The advanced notice calls for greater specificity about how consent forms are written and what information they contain. The document proposes that researchers, sponsors and IRBs adopt strategies to shorten and simplify informed consent documents. The notice invites comment on the value of standardized consent language and the use of oral consent for any research involving surveys, focus groups and interviews conducted with consenting adults, even if identifiers are kept.

The proposed changes would also require written informed consent for collection of biospecimens for research purposes even if no identifiers are kept – but would allow consent to be obtained by the use of a standardized form allowing for unspecified future research. The requirement for written informed consent would not apply to specimens collected prior to the effective date of the new rules.

Establishment of an electronic reporting system for adverse events and unanticipated problems
The advance notice suggests the establishment of a single government-owned website for reporting, storage, and dissemination of adverse events. The notice seeks comment on the use of a set of harmonized definitions and reporting requirements that would fulfill multiple federal reporting requirements.

Data security standards
The advanced notice also proposes mandatory standards for data security and information. The proposed rule would replace the IRB’s authority to evaluate risks to privacy and confidentiality with mandatory data security standards and requirements for all human research. This suggested approach mirrors the current HIPAA Privacy Rule data security requirements including encryption and audit trails.

To submit comments, visit http://www.regulations.gov and search for docket number HHS OPHS-2011-0005. The comment period closes October 26, 2011.

¹ Reforming the Regulations Governing Research with Human Subjects, Ezekiel J. Emanuel, MD, PhD & Jerry Menikoff, MD, JD; New England Journal of Medicine, July 25, 2011

AAHRPP is an independent, non-profit accrediting body that sets rigorous standards for quality and protection of research study participants. To earn AAHRPP accreditation, organizations must provide tangible evidence—through policies, procedures, and practices—of their commitment to scientifically and ethically sound research and to continuous improvement.

“At CGIRB, we are committed to the continuous improvement of our Human Research Protection Program,” said Yvonne Higgins, CGIRB’s Director of Quality Management. “Reaccreditation is evidence of our commitment to the highest level of quality and to upholding our mission–protecting the rights and welfare of human research subjects.”

As an organization driven by quality and innovation, CGIRB became one of the first independent institutional review boards awarded full AAHRPP accreditation in 2004. CGIRB was awarded full reaccreditation in 2007 and 2011. The most recent reaccreditation will extend through fall 2015.

About Copernicus Group IRB

Experience and innovation in ethical review ®

Copernicus Group IRB, established in July 1996, is a leading independent institutional review board (“IRB”) dedicated to ensuring the rights and welfare of research study participants. The IRB provides ethical review of research protocols, investigators, and subject information and consent forms to ensure compliance with federal regulations set forth in 21 CFR, 45 CFR and ICH/GCP Guidelines. CGIRB achieved full AAHRPP accreditation in 2004, reaccreditation in 2007 and 2011, and ISO 9001:2008 certification in 2010. For more information, visit http://www.cgirb.com.

About the Association for the Accreditation of Human Research Protection Programs

The Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP) promotes high quality research through an accreditation process that helps organizations worldwide strengthen their human research protection programs. For more information, visit http://www.aahrpp.org.

To safeguard the rights, safety and welfare of human subjects, clinical research is a shared responsibility among sponsors, investigators, contract research organizations (CROs) and institutional review boards (IRBs). Central to this shared obligation is the meaningful review and communication of new safety information developed during the clinical trial.

Many federal guidance documents pertaining to reporting have been issued in the past few years. Their intent is to assist the research community in interpreting reporting regulations, and to respond to concerns that the overwhelming volume of reports were inhibiting rather than enhancing the protection of human subjects.

A Change in the Reporting Process

But until the reporting process itself changes—among sponsors, CROs and investigative sites—these federal guidance documents will remain largely academic. For reporting to be both effective and sustainable, the reporting burden on all parties must be reduced. Only then will the bar be raised on providing substantive protections for the subjects participating in clinical trials.

Safety reporting is inherently a complicated process. The stakeholders in the research industry all share responsibility for protection of human subjects, but each performs a different function, with different reporting responsibilities and different methods of handling reports. Loose federal regulatory jargon compounds the issue. For example, the investigational new drug (IND) regulations alone use terms such as adverse effect, adverse experience, adverse event and unanticipated problem seemingly interchangeably.

The Role of the Institutional Review Board

Helpful at this point is insight into the role of the IRB—and the negative effect that non-essential reporting has on the review process.

Upon receiving safety-related information, regardless of source, the IRB is obligated to report the following information to its own board members, the institutional official and the Food and Drug Administration (FDA):

• Any unanticipated problems involving risks to human subjects or others
• Any instance of serious or continuing non-compliance with these regulations or the requirements of the IRB
• Any suspension or termination of the IRB approval

An Institutional Review Board must consider action when the potential arises for new or increased risks to humans subjects. Specifically, we look for:

• Modifications to the informed consent document
• Changes to the conduct of the study
• Stopping the study or suspending enrollment until safeguards have been put in place
• Serious or continuing non-compliance, generally at an investigative site

Corrective action plans can include retraining of staff, re-consenting of subjects, or even suspension of enrollment or approval.

When Is an Event Truly Reportable?

Safety reporting to an Institutional Review Board carries an implicit understanding: That the information is important enough that every party is required to be aware of it, and potentially, to take action on it. This understanding is the crux of the entire issue, because it dictates—or rather, should dictate—what is reported to the IRB and when.

At the very least, information delivered to the IRB should warrant the possibility that some action has to be considered. Action may be in response to any of the three types of information required to be reported by the IRB:

• Risks to subjects
• Serious or continuing non-compliance
• Suspensions or terminations of approval

Keep in mind that taming the reporting burden—reducing the amount of non-critical or non-essential information being reviewed—is central to everyone’s ultimate goal of safeguarding and improving the rights and welfare of trials’ subjects. And so the fundamental question becomes clear: When is an event reportable?

An event is reportable when it meets all of the following criteria:

• Is related or possibly related to the research
• Is unexpected in terms of its nature, severity or frequency
• Suggests that the research places subjects or others at a new or increased risk of harm

Generally, to be reportable, an event should be previously unknown to the IRB and require at least consideration of action to minimize the risk to subjects or others (e.g., a safety-related change to the protocol, or disclosure of risk information in the consent document or investigator’s brochure).

By this definition, most adverse events will not meet reporting requirements. The FDA itself has acknowledged that submission of reports that fail to meet the definition of an “unanticipated problem” do not yield useful information about adverse events—and thus add unnecessarily to the reporting burden, hindering the IRB’s ongoing ability to ensure the protection of human subjects.

This is especially true of most IND safety reports, all of which have already been reported to the same regulatory authority to which the IRB must report—the FDA. In a multisite trial, for example, IND safety reports should be fully assessed and submitted to the IRB by the sponsor or delegated CRO, not by individual investigators—if they are reported at all. As the FDA has noted, the sponsor is in the best position to analyze the significance of the information. Put simply, unless an individual safety report contains information previously unknown to the IRB, and it requires IRB action, then it should not be reported.

Of course, nothing is black-and-white—particularly regulated processes that involve so many different parties. Many of our own clients, for example, have SOPs that require reporting of any event. In such cases, the best practice should become to submit these reports to the IRB in batches, with a narrative explaining the sponsor’s analysis—and the clear indication that no change to the conduct of the study is required.

What Must Be Reported?

In our experience, routine safety events are over-reported to the IRB. This results in many wasted hours receiving, analyzing and responding to meaningless information. If the event doesn’t require the IRB to even consider taking an action, there is no reason to report it.

So what must be reported to the IRB? The answer is straightforward—any risk that was previously unknown or unexpected in type, severity or frequency of occurrence. The IRB should be provided with sufficient information to assess what action is needed to address mitigation of the new risk.

When your safety reporting policy meets these guidelines, the downstream effect will be a dramatically reduced burden of reporting on sponsors, CROs and investigators. The end result will be increased time and attention—for everyone in the process—to attend to the truly important task of assuring the safety of the people who participate in clinical trials.