The Future of Work and the Impact on Research Institutions

International organizations such as the World Economic Forum have been researching and analyzing the “future of work” and its implications for economies. Likewise, consulting firms have been predicting the important training needed to prepare workforces for new labor markets. Surveys of company leaders indicate an increasing need for employee upskilling and retraining.

The COVID pandemic and dizzying changes to our work environments accelerated the already-occurring changes in how we work. For research professionals, the changes have impacted how we start-up and manage clinical trials. The breakneck speed with which pharmaceutical companies developed, tested, and deployed COVID vaccines may have been a preview. The clinical trial community should understand the lessons learned from these expedited processes and consider how to prepare for “the next time.”

It remains to be seen which changes will remain for the long term. But some experts say that some permanent changes are inevitable, whether it’s remote patient visits, online collaboration, or remote digital monitoring.

Studies about the future of work tend to focus on the use of artificial intelligence and increased dependency on automation. There are human factors to consider, as well. Managers must define how to run hybrid teams and encourage resilience among workers. The World Economic Forum identifies major changes in three categories:

  • Technology in the form of machine learning, artificial intelligence, and automation
  • Ongoing learning and skill acquisition
  • Talent mobility

This was supported by a report by McKinsey & Company, published in October 2020, that said workers in the life sciences had to double their efforts to focus on patients, leverage technology, and cultivate workplace agility.

Flexible work force

The ability to accommodate the ebb and flow of clinical research activities, or rapid redeployment based on shifting priorities, means that leaders need flexible staffing.

Hybrid work situations will require the need for cross-training among staff and the increased use of external resources to supplement internal staff. Highly responsive teams, augmented by expert hands-on external staff, can ensure sustainability of existing research projects even when new or urgent needs emerge.

Improving patient communication

The requirement to obtain informed consent of individuals before involving them in research is one of the central protections provided for under the HHS regulations at 45 CFR part 46 and  21 CFR 50.

The Revised Common Rule introduced new informed consent standards that focus on providing prospective research participants with information that a reasonable person would want to have in order   to make an informed decision about participation in a research study.  Additionally, the presentation of information to the participant must be organized and include sufficient detail to facilitate the participants understanding of why they may or may not want to join the research study.

These requirements, along with the shift to e-consent and other technologies, have changed not only the language of consent forms but also the process and workflow in obtaining consent.

This is just one example of many patient-centered shifts in the paradigm of clinical research.

Continuous learning

Beyond the required certifications in Good Clinical Practice or foundations for clinical research coordinators, research institutions must offer ongoing upskilling opportunities for staff to keep them up-to-date on the shifting technology and regulatory landscapes of clinical research.

Even prior to the pandemic, online learning was dominating the professional development field. Hiring managers who wanted to cultivate a more diverse and agile workforce were using online solutions such as CITI Program to ensure their skills were up to date.

Leveraging technology for better collaboration and improved workflow

Writing a protocol for a clinical trial has become a complex team sport requiring multidisciplinary input from various sources. Researchers are collaborating with colleagues at their own or other institutions, across clinical disciplines.

The protocol-writing process — from version management to IRB review — can be cumbersome. The use of paper-based systems, or even email, can result in confusion or delays. The result can mean incomplete IRB submissions and frustration for investigators.

Cloud-based guided applications, such as Protocol Builder, can expedite the process by fostering communication and teamwork. These systems build teaching into the writing process, which is essential for residents or new investigators. A complete and compliant protocol submission can result in a smoother IRB review process.

While no one has a crystal ball into the future, many organizations and foresight consultants are in general agreement that the workplace is undergoing a paradigm shift. Research institutions are not immune to these major changes, particularly if they focus on the key areas of change — mobility and flexibility, increased use of technology, and ongoing learning and upskilling.

NIH Announces Consortium to Streamline Gene Therapy Research

The National Institutes of Health (NIH) announced this week that they were joining forces with the Food and Drug Administration (FDA), ten pharmaceutical companies and five non-profit organizations to accelerate the development of gene therapies for rare diseases. The new public-private partnership, called the Bespoke Gene Therapy Consortium, aims to overcome obstacles and streamline the process of developing therapies that could treat diseases that collectively impact millions of people.

The consortium will fund basic and clinical research from a five-year budget of $76 million. This represents an opportunity for investigators. For institutions interested in participating in the expected clinical trials, it may be time to revisit their policies for biosafety and gene transfer. Institutional Biosafety Committees (IBC) are required at institutions that conduct NIH-funded recombinant DNA, or gene therapy, research.

An IBC is concerned for the protection of not only research subjects, but also staff and communities in which the research takes place. The committee has oversight for establishing, monitoring, and enforcing policies and procedures for handling biohazardous materials, such as recombinant DNA.

An IBC works in parallel with an Institutional Review Board (IRB), with special attention to risk assessment for areas including:

  • Study agent
  • Containment levels and procedures required to safely handle the study agent
  • Preparedness of the facility and its personnel
  • Potential impact to the environment

Activities of the IBC include:

  • Review agent characteristics (e.g. virulence, pathogenicity, environmental stability)
  • Determining the appropriate biosafety level for physical and biological containment, as required by the NIH Guidelines
  • Inspection of facilities, procedures, and practices
  • Evaluating the training and experience of the personnel involved in the research
  • Confirming appropriate policies and procedures are in place for handling spills or accidents to minimize exposure to or contamination from any potentially hazardous material
  • Reporting significant events or violations to regulatory authorities including NIH and institutional officials
  • File an annual report with the NIH

NIH requires that an IBC have at least five members who collectively have broad experience and expertise that allows them to conduct such assessments. This may include members with technical expertise in potentially hazardous biological materials, human research protocols, regulatory requirements, and in the health and protection of the community and environment. Additionally, at least two members must be unaffiliated with the organization conducting the research, and these members should represent the interest of the surrounding community with respect to health and protection of the environment.

The establishment and funding of the Bespoke Gene Therapy Consortium will increase the opportunity for investigators to participate in basic and clinical research to address significant unmet medical needs of patients. The safe conduct of experiments involving recombinant or synthetic nucleic acid molecules depends on the individual conducting such activities, as well as having appropriate safety mechanisms at the institutional level.

BRANY offers IBC services that can help expedite the review of research that involves recombinant DNA (“rDNA”) or synthetic nucleic acid molecules, or DNA or RNA derived from recombinant or synthetic nucleic acid molecules, providing rigorous biosafety oversight so that institutions can focus their efforts on scientific research and advancement. Contact us for more information.

When an Investigator is also a Sponsor

When investigators embark on designing, writing, and initiating the clinical trial, their responsibilities are just beginning. The FDA calls these investigators “sponsor-investigators (SIs)”. A sponsor-investigator is an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. In other words, in an investigator-initiated trial, the researcher is both the investigator and the sponsor, and therefore must handle the responsibilities for both roles.

The FDA provides guidance for individual investigators planning to conduct clinical investigations of FDA regulated drug(s) or device(s) for an indication that does not appear in the approved labeling for the product. Depending on the origin of the funding for the trial (e.g. federal funding) regulations by the U.S. Department of Health and Human Services Office for Human Research Protections (OHRP), 45 CFR 46 known as The Common Rule, may also be applicable.

In most cases, institutional policies and guidance fall into two major categories: protecting human subjects and ensuring the integrity of the data from clinical investigations. This is true for all research trials.

All investigators in interventional drug studies must complete and submit FDA Form 1572 (21 CFR 312.50), which specifically outlines certain responsibilities and obligations including agreeing to personally conduct and supervise the investigation.

Investigational New Drug (IND) or IDE Applications

Some protocols may require the investigator to submit an investigational new drug (IND) or an investigational device exemption application. However, a sponsor-investigator may not be required to submit an IND for a study of a lawfully marketed drug if the criteria outlined in the FDA regulations at 21 CFR 312.2(b) for an IND exemption are met. Investigators should confirm if the protocol is exempt from this requirement by reviewing the regulations. If sponsor-investigators are uncertain if the exemption criteria are met, they should seek advice from FDA.

For trials involving medical devices, the Investigational Device Exemptions (IDE) regulation (21 CFR 812) must be considered. Under this regulation medical devices are generally categorized as significant risk or nonsignificant risk devices. Significant risk devices studies must have an IDE application approved by FDA before any research may begin.

Conduct Good Clinical Practice (GCP)

GCP is an international ethical and scientific quality standard for clinical trials with a primary objective of protecting human rights. Compliance with this standard helps to provide assurance that the rights, safety, and well-being of trial subjects are protected. FDA has adopted GCP as guidance for carrying out clinical trials. FDA regulations relating to good clinical practice and clinical trials include:

Monitoring and Reporting

Good Clinical Practice (GCP) guidelines also describe the requirements for quality management in clinical trials to further ensure the protection of participants and the reliability of trial results. Investigator-sponsors have specific responsibilities for monitoring trials to confirm the trial is conducted and the data generated, recorded, and reported are in compliance with the protocol, GCP, and the applicable regulatory requirement(s).

The methods used to assure quality should be proportionate to the risks in the trial and the importance of the information collected. Methods for monitoring clinical trials range from on-site data verification to centralized data monitoring using statistical analytics to identify areas of risk.

Investigators who do not comply with these regulations and standard operating procedures run significant risk of liability and federal investigation. The FDA has outlined a specific process for investigating non-compliant investigators that includes disqualifying investigators from further research.

The regulatory landscape is constantly shifting and can pose some challenges, particularly for new investigators. Working closely with regulatory experts through the steps, as well as taking courses on GCP, can minimize the risks, protect patients, and ensure research integrity.

Further resources

FDA Guidance for Industry: Investigator Responsibilities
https://www.fda.gov/media/77765/download

FDA Guidance for Sponsor-Investigators
https://www.fda.gov/media/92604/download

ACRP Guide to FDA Form 1572
https://acrpnet.org/2019/04/25/revisiting-the-form-fda-1572/

Best Practices for Remote IRB Meetings

The campus closures necessitated by the pandemic in 2020 forced many research administration officials to adopt virtual meetings to continue their work. People scrambled to set up their home offices, to secure Wi-Fi networks and create accounts on videoconferencing services. The Internet offered dozens of articles on how to improve online meetings to encourage engagement and collaboration.

Now, nearly a year later, organizations and companies continue to struggle to run efficient and effective virtual meetings. Online meetings have challenges that many of us have experienced. It’s difficult to read body language or have eye contact. Some technologies have lag times that cause people to talk over each other. Virtual meeting attendees are more prone to interruptions and distractions.

The pandemic forced a dramatic and rapid switch to virtual meetings for Institutional Review Boards, as well. Over half of attendees at a webinar hosted by CITI Program in February 2020 indicated that they held IRB meetings exclusively in person, with about another 40 percent conducting hybrid meetings. Only six percent indicated virtual-only meetings.

BRANY’s IRB has been meeting virtually for several years. These are some of the best practices we have learned, as well as highlights from the CITI webinar mentioned earlier. A recording of the webinar is available on the CITI Web site.

Beyond the usual accommodations required of virtual meetings, Institutional Review Boards have specific regulatory requirements regardless of whether they meet in person or virtually. Ensure that your meetings comply with the regulatory components of 45 CFR 46.111 and 21 CFR 56.111.

Leverage Supporting Technologies
Virtual meetings can be supported with technology-driven solutions specific for managing IRBs. IRB management systems can be very robust and help streamline the IRB review process by enabling online submissions, sending electronic alerts, and storing key documentation, such as IRB policies and determination letters.  Additionally, these tools are extremely useful for generating meeting agendas, meeting minutes and can be utilized during IRB meetings to share relevant documents with the entire IRB committee via video conferences.

Be Consistent
Having a predictable and consistent agenda and process can help keep the meeting running smoothly and on time. Your IRB may want to consider implementing standard meeting procedures, such as those found in Robert’s Rules of Order, with the specific steps for reviewing protocols. It may be useful to distribute these review guidelines to the IRB members as well as the investigators.

Likewise, meetings should be regularly scheduled and on members’ calendars. Standing meeting days and times can increase the likelihood of convening a quorum, one of the regulatory requirements of IRBs.

Provide Training
Training members on the remote meeting platform will help the meeting to run smoothly and reduce the amount of disruption that can occur when people are not proficient at the audio and video technology. The following areas are particularly important:

  • Signing in properly especially when using both a computer and phone. If audio is active on both devices it will create an echo, which is extremely distracting to all participants
  • Using the mute function when others are speaking
  • Remembering to unmute
  • Slow internet speed can cause delays in audio transmission

Agree on Specific Roles
Running a successful IRB meeting requires several people, and their roles should be clearly defined in advance. An IRB coordinator or meeting specialist, for example, can send calendar reminders, links to the necessary materials, and instructions for dialing in to the meeting. Another critical role in an IRB meeting is that of the scribe, or minute-taker.  Accurately capturing the vote count for items reviewed by the committee is also a key responsibility.  Completing a roll call to verbally verify voting may also be a task assumed by this role.

Set Expectations for Behaviors and Procedures
In addition to having clearly defined roles, it is important that the committee understand and consent to certain expected behaviors. For example, it is important to agree on these questions:

  • Does the committee require that cameras be turned on for video calls?
  • How will the chair acknowledge speakers to ensure each individual has an opportunity to share thoughts?
  • How will notes be taken and shared?
  • When will deliberations be considered complete and voting can commence?

Advise meeting participants in advance if you are recording the meeting.

Practice Active Listening
Because the usual dynamic of in-person meetings is not realistic with virtual meetings, it is important to use active listening skills to ensure that people are not only heard, but also understood. Aside from paying attention and withholding judgment, participants — led by the example of the chair — can use skills such as reflecting, clarifying and summarizing. This also helps improve accuracy for notetaking.

While many people are anxious to get back to their offices and resume in-person meetings, the reality of virtual meetings — at least some of the time — is likely to remain a bit longer. Even beyond the pandemic, IRBs should be prepared to respond to possible future emergency situations that necessitate virtual meetings. These and other best practices can make virtual IRB meetings not only smooth, but compliant with regulations.

The Importance of Real-time Data and Safety Monitoring

Researchers at Baylor College of Medicine Houston announced this week that they were stopping a clinical trial investigating the efficacy of convalescent plasma therapy in the treatment of patients with COVID-19. The reason, according to the principal investigator, was that statisticians had deemed the NIH-funded study to be futile. In other words, even with more patients enrolled in the study, the experts monitoring the data did not believe there was a realistic chance that convalescent plasma therapy would demonstrate efficacy.

Behind the headline is another important consideration: the importance for Institutional Review Boards (IRBs) to ensure that studies they approve have strong data and safety monitoring plans (DSMP). Data and safety monitoring functions are distinct from the requirement for study review and approval by an Institutional Review Board (IRB).

“Since IRB review occurs only at certain intervals, real-time data monitoring is typically done by a formal Data Safety Monitoring Board (DSMB) or another similar independent committee, as designated by the DSMP,” according to Linda Reuter, BRANY’s IRB Director. “As such, it is crucial for IRBs to consider the IRB approval criteria that risks to subjects are minimized and the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects by confirming that there is a plan to analyze the data at the appropriate intervals.”

“The IRB must determine that the provisions for data and safety monitoring are appropriate in order to approve a protocol,” adds Raffaella Hart, BRANY’s Sr Vice President for IRB and IBC Services. “Clinical trials should have a provision for data and safety monitoring that corresponds to the risks of the study.” The NIH has guidance on determining which studies require a Data and Safety Monitoring Board (DSMB). Multi-site clinical trials involving interventions that entail potential risk to the participants require DSMBs.

Review by an independent monitoring committee is especially important for multicenter clinical trials, as data from one site may not be enough to notice a safety signal at an early stage, but when data from multiple sites are aggregated and analyzed by the safety committee certain safety signals may become evident.

The method and degree of monitoring varies from one clinical trial to another and is based on the degree of risk involved, as well as the size and complexity of the trial. While not all clinical trials require a data and safety monitoring board, the NIH does set minimum standards for monitoring, including ensuring that monitoring is timely and effective and that those responsible for monitoring have the appropriate expertise to accomplish its mission. Monitoring plans typically include the following:

  • Safety reporting requirements and procedures
  • Rules for when to conduct interim analyses to assess safety and/or efficacy
  • How the study will comply with any applicable regulatory requirements
  • How the study will monitor site performance, including patient recruitment
  • How to protect data integrity and participant confidentiality
  • Statistical analysis procedures

Data and Safety Monitoring Board determines the safe and effective conduct of the trial, and establishes rules for deciding when it may be time to conclude the trial. The committee makes this important decision based on evaluating if significant benefits or risks have developed or the trial is unlikely to be concluded successfully. This was the case in the above-mentioned plasma therapy trial.  DSMBs should include clinical trial experts, biostatisticians, bioethicists, and clinicians knowledgeable about the disease and treatment under study. Ideally, members should not have a vested interest in the outcome of the study, in order to avoid conflicts of interest.

“Early and ongoing data analysis is critical to the safety and protection of study participants,” says Ms. Reuter.

Chart Review Studies During and After a Pandemic

The current global pandemic combined with electronic medical records and data visualization technologies have resulted in unprecedented advances in real-time tracking of SARS-CoV-2, the virus that causes COVID-19, across countries, states and local communities. As the situation evolves, there will be ample opportunity and increased need for both retrospective and prospective COVID-19 research studies that involve the review of medical records.

The rapidly evolving situation in this global pandemic requires investigators to design and write protocols quickly for IRB review. A guided protocol-writing experience, as with ProtocolBuilder, streamlines the process, ensures regulatory and institutional compliance, and facilitates collaboration among researchers.

In medical record review studies, also called a “chart reviews,” a researcher may collect and analyze information that was originally collected for a different purpose, also referred to as a secondary use of data. It often involves the collection of data from medical records in order to evaluate possible relationships between different variables and specific outcomes measures. An investigator may assess biomedical, treatment or demographic variables by reviewing various elements of a medical record. These may include lab results, physician or summary notes, admission and discharge summaries, etc.

Chart review studies can also be designed to collect prospective data, meaning the patient data does not exist at the time the protocol is submitted to the IRB for initial review. While many chart review protocols may qualify for a determination of exempt status from the IRB or expedited IRB review due to the minimal risk to research subjects, these studies are still subject to IRB review and HIPAA privacy protections. A guided and structured protocol-writing experience can accelerate the process while enhancing compliance, supporting collaboration, and saving time.

A chart review study protocol will generally include the following key elements:

  • A synopsis — includes the objectives and high-level summary of the study elements, including a study flow chart
  • Introduction and background — includes the protocol statement of compliance
  • Rationale — includes the problem statement, risks and benefits
  • Literature review — a synthesis of the current literature to establish the relevance of the problem and description of the literature that supports the need for the study
  • Research design and methods — includes the study population and duration of the study. For chart reviews, a date range that indicates the timeframe for which records will be queried (e.g., a review of all ER visits between 1/1/2020 and 7/1/2020)
  • Data collection and handling — includes a plan for maintaining subject confidentiality and privacy, how data will be collected and stored
  • Statistical analysis plan — how the data will be analyzed to achieve the objectives

Chart review protocols are emerging as an important methodology in understanding COVID-19. Given the rapidly-developing nature of the global pandemic, the need for prompt writing and review of these protocols is critical to the ongoing effort to understand the situation.

ProtocolBuilder, a cloud-based research protocol-writing tool, can help improve the quality and consistency of clinical research protocols to make internal and IRB review processes more efficient.

 

Further Resources

ProtocolBuilder
https://protocolbuilderpro.com/

Research Study Design
https://about.citiprogram.org/en/series/research-study-design/

Research and HIPAA Privacy Protections (part of Comprehensive CIP Course for Advanced Learners)
https://about.citiprogram.org/en/course/comprehensive-cip-course-for-advanced-learner

New CITI Program Courses and Webinar Help Researchers and Institutions Meet Regulatory Requirements

(Miami, FL) — The Collaborative Institutional Training Initiative (CITI Program), a division of BRANY, has announced new online courses and webinars designed to help research professionals understand and comply with regulatory requirements for clinical trials.

The three courses and webinars address critical regulatory requirements:

  • Transitioning research to the Revised Common Rule
  • Protocol registration and disclosure on ClinicalTrials.gov
  • The role of principal investigators in meeting regulatory requirements

Transitioning Research to the Revised Common Rule: The What, How, and Why, a webinar that outlines considerations and challenges for transitioning pre-existing research to the revised Common Rule, as well as required documentation and tips for IRB review, is offered to both institutions and individual learners.

Designed for research professionals, including investigators, institutional review boards and research staff, the webinar reviews pre-2018 and 2018 versions of the Common Rule, including factors an organization may want to consider when deciding whether to transition a pre-existing study (or studies) to comply with the revised Common Rule, and strategies for the management and communication of transition decisions.

The webinar is presented by Karen Christianson, RN, BSN, a principal with HRP Consulting Group.

Recently published research demonstrates that many research institutions are not prepared to meet current requirements for registering and reporting clinical trials. A new course addresses this gap.

Protocol Registration and Results Summary Disclosure in ClinicalTrials.gov, an innovative video-enhanced course, guides learners through critical parts of the regulations and provides a step-by-step guide to data entry. This course can help organizations/investigators clearly understand protocol registration requirements to avoid the risk of significant civil monetary penalties or loss of NIH grant funding due to non-compliance with protocol registration and results reporting.

Biomedical PI focuses on key topics essential to the biomedical investigator’s role and responsibilities in conducting a clinical investigation of a product regulated by the U.S. Food and Drug Administration (FDA). This role-based course covers supervision, delegation, management, reports, and communication for investigators.

These courses, along with dozens of others available at CITIprogram.org, train investigators and research professionals to understand and meet research ethics standards and compliance requirements.

About CITI Program

The Collaborative Institutional Training Initiative (CITI Program), a division of BRANY, is dedicated to promoting the public’s trust in the research enterprise by providing high quality, peer-reviewed, web-based educational courses in research, ethics, regulatory oversight, responsible conduct of research, research administration, and other topics pertinent to the interests of member organizations and individual learners.

 

The Revised Common Rule and Informed Consent: Public Posting

Public Posting

An important provision in the Revised Common Rule is the requirement to post, to a publicly-available federal Web site, a copy of an IRB-approved version of the consent form that was used for enrollment purposes for each clinical trial conducted or supported by a federal department or agency. The Office for Human Research Protections (OHRP) has identified two publicly available federal websites that will satisfy the consent form posting requirement in the revised Common Rule: http://ClinicalTrials.gov and a docket folder on http://Regulations.gov. It is possible that additional sites may be identified in the future.

The consent form will need to have an up-front concise and focused presentation of the key information as required by 46.116(a)(5).

The specific requirement is that an IRB-approved consent form that was used for enrollment purposes be posted. There is no requirement to post multiple forms for multicenter studies, or for a study that has separate consent forms for different subject groups (e.g., adults versus pediatric participants). Also, for consent forms that underwent revision over the course of the study, the final rule does not stipulate that the posted document be the most recently approved version.

The posting can take place any time after the clinical trial is closed to recruitment, and no later than 60 days after the last study visit by any subject, as required by the protocol. Information that should not be made available on a federal website, as determined by the federal department or agency supporting or conducting the clinical trial, can be redacted.

The purpose of the new provision is to increase transparency, which some feel will lead to improved consent form quality. The commentary to the Final Rule, describes how having  an easily accessible repository of such forms freely available for analysis and public discussion will foster public discussion and  create multiple opportunities for improving these forms, and thereby improve one of the most important aspects of our human subjects protections system.

For More On The Revised Common Rule and Informed Consent, see our previous article on Consent Waivers

The Revised Common Rule and Informed Consent: Consent Waivers

The Revised Common Rule and Informed Consent: Consent Waivers

The Revised Common Rule has a few important changes regarding consent waivers.

Under the revised Common Rule, broad consent is provided as an alternative to the informed consent requirements for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens. If an individual was asked and refused to provide broad consent, the IRB is prohibited from waiving informed consent at a later date for the use of the subject’s identifiable private information or identifiable biospecimens in a secondary study. This means that this information must be tracked. This may be complicated, particularly for larger health care institutions and systems, and therefore the broad consent mechanism may not be widely utilized.

Of note is that the use of the individual’s materials in a nonidentifiable manner in secondary research continues to be permissible, even if there was a refusal to broad consent, since this particular use would not otherwise require a waiver of informed consent since the activity does not constitute research with human subjects.

The Revised Common Rule also adds a new waiver criterion. In order to waiver or alter consent, the IRB must find and document the following:

  • The research involves no more than minimal risk to subjects;
  • The waiver or alteration will not adversely affect the rights and welfare of the subjects;
  • The research could not practicably be carried out without the requested waiver or alteration;
  • (New as of January 21, 2019) If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format; and
  • Whenever appropriate, the subjects or legally authorized representative will be provided with additional pertinent information after participation

The term “practicably” has not been clarified in the revised rule.

In the case of recruitment and screening of research subjects, the pre-2018 rule required an IRB to determine that informed consent can be waived under the .116(d) criteria before investigators could record identifiable private information for the purpose of identifying and contacting prospective subjects for a research study. Although not considered a “waiver,” under the new rule, an IRB can approve an investigator’s proposal to obtain information directly from a prospective subject, or to obtain already collected identifiable information or identifiable biospecimens by accessing records or stored biospecimens, for purposes of screening, recruiting, or eligibility assessment, without the informed consent of the prospective subjects.

The Revised Common Rule’s section on waivers or alterations of consent can be complicated, so it is important for research professionals, researchers and IRBs to review the changes and the exceptions.

 

For More On The Revised Common Rule and Informed Consent, see our previous article on Broad Consent

The Revised Common Rule and Informed Consent: Broad Consent

Gene Therapy Research — Is Your Institution Ready?

Recent news about approved immunotherapy and gene therapies has generated excitement around the possibilities of treating difficult diseases. Organizations have increased funding in this area, including a recently announced $1.3 million grant in funding by the Alliance for Cancer Gene Therapy for research in gliobastoma, sarcoma and ovarian cancer.

The increased attention and funding means that more research institutions may enter this exciting field of research. However, institutions may not be fully aware of the specific NIH guidelines and requirements for gene transfer research in addition to IRB review. An institution that receives NIH funding or conducts NIH funded recombinant DNA research is required to follow the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (“NIH Guidelines”). Even if the funding source is a private entity, it is still advised that institutions comply with the NIH Guidelines to ensure the safety of research teams and the communities they serve.

The NIH Guidelines define human gene transfer as the deliberate transfer into human research participants of either:

  • Recombinant nucleic acid molecules
  • DNA or RNA derived from recombinant nucleic acid molecules
  • Synthetic nucleic acid molecules, or
  • DNA or RNA derived from synthetic nucleic acid molecules that meet certain criteria

An institution that engages in gene transfer must establish an institutional biosafety committee (IBC). This committee can be administered either internally (by the institution), or by an experienced external group. The IBC must have at least five members, two of whom must not be affiliated with the institution. The role of the IBC is distinct from the role of an Institutional Review Board (IRB). The IRB’s focus is on protecting the rights and welfare of research participants, whereas the IBC assesses the containment levels, facilities, procedures, practices, and training and expertise of personnel involved in recombinant or synthetic nucleic acid molecule research.

Research involving recombinant or synthetic nucleic acid molecules requires IBC review because additional safety measures are needed. The risk assessment for these agents must be done by qualified experts experienced in biosafety guidelines, including physical and biological containment requirements. Those conducting this research need to understand and identify the biosafety level of the particular investigational agent — level one being the lowest level and level four being the highest. Each level has specific parameters that must be met with relation to precautions needed, such as containment levels, staff training requirements, and the experience required of those handling the agent.

Risk is assessed by evaluating the following:

  • Staff training — are they trained in handling the agents according to guidelines and standard operating procedures?
  • Protocol — does the protocol outline how the agents are handled, including waste precautions and decontamination procedures?
  • Recordkeeping — how are records documented and kept?
  • Procedures — how and where is the agent or drug constituted?
  • Community safety — what mitigation steps are in place to protect the community?

While the prospect and promise of human gene transfer research is exciting, institutions and researchers must understand the requirements when working with these investigational agents.

When research involving recombinant DNA is NIH funded or conducted at a site that receives NIH funding, failure to comply with the NIH Guidelines could risk that funding or result in additional requirements by NIH for the conduct of such research. Leveraging an external team of experts fluent in biosafety, the NIH Guidelines, and IBC administration can provide an immediate framework for an institution to build upon that will ensure the safety of local research teams and the surrounding communities in an ethical and efficient way.

Protocol Builder Launches Protocol Template for Social-Behavioral – Educational Research

BRANY announced today the release of a new research protocol template specifically designed to address the unique needs of social-behavioral-education researchers, as part of Protocol Builder®, a secure, cloud-based protocol writing application.

“Social and behavioral research is distinct from biomedical research,” says Jeffrey Cohen, PhD, a principal with HRP Consulting Group, also a division of BRANY. “The process of writing a protocol can be more subtle than an interventional drug study, for example.”

“Although historically many social behavior researchers have not developed full protocols for their research prior to submitting to an IRB, many institutions are now requesting social behavioral protocol development templates as research in this area continues to grow,” says Kimberly Irvine, Executive Vice President and Chief Operating Office for BRANY. BRANY now also has a social behavioral IRB as part of its comprehensive IRB service offering. This new template is a response to our customers’ requests for a tool that provides them with a more comprehensive approach to protocol development for social and behavioral research.

The specially-designed template provides a guided, step-by-step protocol-writing process for investigators who specialize in psychology, nursing, education and other disciplines that are focused on behavioral and social functioning. It is one of several standard and customizable templates offered through Protocol Builder®, including the new NIH IND/IDE template.

Protocol Builder® is currently in use at leading academic medical centers and universities as a tool to foster compliance with institutional protocol writing standards among their investigators, including residents and fellows.

Protocol Builder® is a division of BRANY, the leading provider of research support services to hospitals, academic medical centers and investigators. In addition to Protocol Builder®, BRANY offers a wide array of services designed to improve research efficiency and quality. These include IRB, human subject protection consulting and continuing education.

BRANY IRB Services

BRANY IRB, AAHRPP-accredited since 2006, has been providing high quality, customer service oriented IRB services to client for more than 18 years. BRANY IRB specializes in , single IRB (sIRB) for multi-site research, and SBER IRB review by a committee with expertise specific to social, behavioral and education research.   BRANY’s “Connected IRB” model has provided institutions with a customized solution that results in high quality human subject protection oversight, as well as efficiency for industry sponsored and investigator initiated research.

HRP Consulting

Through its consulting division, the HRP Consulting Group, BRANY provides institutions human subject protection and research compliance consulting services.

CITI Program

The Collaborative Institutional Training Initiative (CITI Program) at the University of Miami, also part of BRANY, is the leading provider of online research ethics education courses and materials. CITI’s web-based training materials serve millions of learners at academic institutions, government agencies, and commercial organizations in the U.S. and around the world. CITI Program now offers the CTSA created GCP – Social and Behavioral Research Best Practices for Clinical Research course.*  This course introduces GCP principles and discusses how they apply to clinical trials using behavioral interventions and social science research.