Telehealth, Clinical Research and Informed Consent
By most any measure, one of the biggest impacts that COVID-19 has had on the practice of medicine is the shift toward more telemedicine visits. Although the practice of delivering health services over the phone or the Internet has been around for some time, it wasn’t until the pandemic forced communities to close that clinical practices started to explore the use of technologies to continue monitoring patients remotely.
The global health crisis has forced both health care providers and regulatory agencies to pivot toward digital health services. Clinical research is no exception. Many clinical research studies were put on hold in the early days and weeks of the pandemic in the United States. Researchers and their staff were deployed to support COVID-19 efforts. Regulatory agencies had to adapt guidelines for HIPAA and other issues for the new environment. Health insurers developed policies for telemedicine and reimbursement.
Although clinical research in COVID-19 still seems to dominate at research institutions, protocols not related to COVID-19 are starting to return. Studies that were paused are also being resumed, albeit slowly and cautiously. Each institution has to assess risk based on local risk factors and patient populations. For studies that are primarily computational, or do not require in-person interventions, telemedicine may continue to dominate.
For research professionals, one critical issue is the process for consenting, or re-consenting, patients. For studies that were paused, investigators may need to re-consent patients due to necessary changes in the protocol. Participants may have to confirm their willingness to continue their participation in a trial.
These and other issues require consideration of the process of obtaining consent. Research coordinators, while familiar with the protocols, may need to adapt to the method of consent and how they explain the studies to patients via these technologies. The 2018 regulatory changes to consent forms that require a concise summary may be helpful in helping to communicate with potential participants. The remote consenting process may require more dialogue with the patient to ensure understanding.
These new processes can be an adjustment for research coordinators or others obtaining consent. Proper training on process is critical to ensure informed consents are conducted appropriately and continue to protect human subjects.
CITI Program, a division of BRANY, is hosting a webinar on informed consent on September 30, 2020 at 2PM EST.
The Critical Issues Sites Need to Track During a Clinical Trial
Congratulations! You have gone through all the necessary steps to launch a clinical trial. Now it’s time to move on to the next one, right? Wrong! A successfully managed clinical trial requires ongoing tracking throughout its duration. Careful tracking ensures your research organization remains compliant and that your site is compensated properly for the study.
Follow our series on the key critical issues you need to track throughout a clinical trial.
Part One — Protocol amendments
This is likely one of the most common and time-consuming of the issues that require tracking. A Tufts University study found that over half of sponsored studies have at least one significant amendment.
Protocol amendments are inevitable, and some trials undergo multiple amendments throughout their duration. But some revisions are so significant it could feel like starting all over again.
There are generally two kinds of protocol amendments — administrative updates and substantive protocol revisions. Administrative changes are typically minor, and may involve grammar, wordsmithing, punctuation or small editorial changes. Significant amendments are any changes that may impact the safety of participants, and can include any change to the design of the protocol, including:
- Change to the dosing or duration of participant exposure to a drug
- Change to the design of the protocol, such as the inclusion or exclusion criteria or the addition of treatment arms
- Addition of new tests or procedures
IRB review and approval is required in order to carry out the visits and procedures that are part of the amended protocol. IRBs often require the following information when submitting an amendment:
- A description of the differences between the original protocol and the amendment
- Revisions to the informed consent, if applicable
- Revisions to any marketing or patient recruitment materials
Protocol amendments can impact patient recruitment efforts. In fact, some protocol amendments may also affect a site’s ability to enroll if there are significant changes to inclusion or exclusion criteria. Often the consent form must also be revised to reflect the changes to the protocol. Patients may need to be re-consented with the updated, IRB approved version of the consent form so they can be made aware of changes in protocol procedures.
Depending on the scope of the protocol amendment, your research site should review the study budget, as the necessary procedures may have changed or new procedures and visits may have been added. In our experience, amendments have an impact in roughly half of all study budgets. A full review of the budget, and possibly a revised Medicare Coverage Analysis, may be necessary.
Create a checklist
The more you prepare and plan for protocol amendments, the smoother the process to implement the amended protocol. The use of a checklist or systematic approach will ensure that no steps are overlooked.
Whenever there is a protocol amendment, clinical research coordinators should make sure they update the following:
- IRB/IEC and other regulatory submissions
- Informed consent documents, including oral consent scripts
- Marketing, advertising or recruitment materials
- Sponsor contract, particularly if there is an impact to the budget, and coverage analysis, if applicable
Studies have shown that protocol amendments can impact the cost and duration of clinical trials. But with some careful preparation, clinical research coordinators can ensure a smooth administration of the changes.
The Revised Common Rule and Informed Consent: 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 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
While the industry waits for additional guidance on the Revised Common Rule, there are some aspects that are worth taking note now. This is a series of blog posts that address various important changes for research professionals to keep in mind as they implement the Revised Common Rule.
BLOG POST #2 — Broad Consent
One of the significant changes in the Revised Common Rule is the introduction of Broad Consent., a new type of consent intended to serve as a substitute for traditional informed consent in certain circumstances. “Broad Consent” is a very specific term in the revised regulations used to describe a regulatory pathway, and is different from the concept of obtaining consent for future use of information or specimens under the prior regulations.
The new regulations also provide two new exempt categories for the storage, maintenance and research use involving identifiable private information or identifiable biospecimens when broad consent has been obtained.
Broad consent may prove to be problematic, particularly for large medical centers or health care systems, due to the documentation requirements. The regulations stipulate that an IRB cannot waive consent for storage, maintenance, or secondary research use of the identifiable information or identifiable biospecimens if an individual was previously asked to provide broad consent and refused. Such tracking requirements may make broad consent very difficult to implement, and may limit its usefulness.
A Broad Consent Form must contain certain elements in order to be valid. The following elements are unique to broad consent, and must be included:
- A general description of the types of research that may be conducted with the information or biospecimens that a reasonable person would need to make a determination
- A description of the identifiable information or biospecimens that might be used in research, whether sharing might occur, and the types of institutions or investigators that might conduct such research
- A description of the period of time allowed that the information or biospecimen would be stored and maintained or used for research purposes (may be indefinite)
- Statement that the subject or LAR will not be provided details about specific research studies that might be conducted using the information or biospecimens including the purposes of the research and that they might have chosen not to consent to some of those specific research studies
- Results may not be disclosed to subjects
- Contact information for questions about rights and storage and use of the information and specimens, and whom to contact if the event of a research-related harm
These elements are required in every broad consent document, and cannot be waived.
For More On The Revised Common Rule and Informed Consent, see our previous article on Concise Summary