We strongly support the intent behind many of the recommendations laid out in the Advanced Notice for Proposed Rulemaking (ANPRM) analysis. Modification of a complex system such as the existing implementation of the Common Rule can have unintended negative consequences. We urge Office of Human Research Protections (OHRP) to work closely with stakeholders during the next steps in order to provide explicit, clear guidance that will enhance patient protection while minimizing non-value-added process.
The scope of issues addressed by the ANPRM is very broad. OHRP may want to consider phased implementation of new regulations. In addition, it’s critical to develop an evaluation plan head of implementation, to ensure that the impact of the changes can be evaluated, and appropriate course-corrections be made.
Ensuring Risk-Based Protections:
We strongly support the concepts laid out in the ANPRM analysis which aim to correlate the ‘intensity’ of institutional review board (IRB) review with the possible risk to research subjects. The current default practice wastes time and resources, as documented in the ANPRM analysis and elsewhere. For example, we are involved with a research study looking at a variety of ways to educate patients about clinical trials. As part of our responsibility, we developed a poll to invite patient advocates to participate in a focus group at a national meeting. The academic center affiliated with the study required that the poll receive expedited review. As a result of the review, we were required to change a few words in the invitation – the required change was subjective, and had nothing to do with participant ‘safety’. We would argue that an invitation to a focus group was safe, and the IRB had no reason to review it.
Streamlining IRB Review of Multi-Site Studies:
We support mandating one IRB of record. We are concerned that if research organizations are “encouraged” to use a single IRB, the default judgment by the organizations’ risk management team will be to perform a local IRB review in addition to the central IRB.
We feel that local IRB review does not add to protection of human subjects in multi-site trials. In talking with advocates involved with IRB and informed consent across the country, we have heard that many “local” issues are centered on institutional protection rather than patient protection. In addition, we hear that training standards vary between institutions. Ideally, central review of multi-site trials will free up local resources which will allow local IRBs to focus on patient protection in single-site trials. In the United Kingdom, they have found that central review actually improves patient protection because the central reviewers receive extensive and consistent training which allow them to evaluate patient risks effectively.
IRB-shopping is a real concern. We urge OHRP to probe this issue during the rule-making process, as it is critical to patient protection. Perhaps this is an area where clear sanctions for both lax IRBs and institutions that shop for them could be developed and applied.
Improving Informed Consent
The informed consent document
The ANPRM analysis says that informed consent documents “often function as sales documents, instead of as genuine aids to good decision making.” According to our advocates who are involved with the development of informed consent documents, the documents seem to function more as legal documents designed to protect institutions against potential lawsuits. The National Cancer Institute (NCI) is working on an initiative designed to cut length while improving patient comprehension, which we feel addresses many of the issues raised in the ANPRM. Simple changes such as describing how patients will feel (tired) instead of medical terms (anemia), and adherence to plain language principles will improve understanding. Explaining how the experimental treatment compares to standard treatment will help patients make an informed choice between the two. Since the length of documents tends to increase over time, we feel that page count, font size and white space requirements should be set. Exceptions can be made for research that actually requires additional information; we feel that researchers need to justify longer consent documents.
Institutions are often reluctant to provide additional information to patients in the context of the trial if the information has not been IRB-approved. We urge OHRP to consider pre-approving specific forms of information as appropriate to provide to patients in the context of a trial. Booklets, such as those developed by the NCI on specific diseases and side effects, are created with high standards and can help patients understand their disease and treatment as well as the trial.
We applaud the intent behind requiring patient understanding prior to trial enrollment. At the same time, we’re troubled by how this would actually be implemented. Would institutional risk managers require that patients complete a quiz? Who would assess patient understanding?
As noted, the consent process itself is critically important. In theory, consent is performed by the physician involved. In our experience, consent is often performed by others such as the Certified Research Associates who may or may not have been trained in the process. This issue wasn’t specifically addressed in the ANPRM; however, we hope you consider it during the rule making.
Consent for Biospecimens and Information
The ANPRM analysis says, “Some critics, including potential and former research subjects, object to research performed on a person’s biospecimens without consent. This was recently highlighted in the book, The Immortal Life of Henrietta Lacks.” On the other hand, a huge amount of productive research has been performed on biospecimens without consent.
We support the C-Change analysis and feedback in this area. Their analysis is available here. We urge you to consider their comments carefully – they address concerns around potential over-regulation, and the negative impact on research. Their analysis raises legitimate concerns which need to be addressed in the final rule.
Data Collection to Enhance System Oversight
We strongly support efforts to identify meaningful serious adverse events (SAE) identified during research. The Food and Drug Administration (FDA) announced a final rule in September 2010 that – once implemented – could greatly improve patient safety and decrease mindless paperwork. As always, implementation is complex. We assume that the ANPRM recommendations are being developed in conjunction with FDA’s efforts.
A project conducted by the Clinical Trials Transformation Initiative (CTTI) documented problems in the existing system, and also looked at consumer expectations of SAE reporting. Interestingly, consumers have high and largely unrealistic expectations of SAE reporting, and expect to be informed promptly when any SAE occurs. This points out a gap between what patients are told in the informed consent, and the reality of SAE reporting. Our interactions with patients indicate that patients consider safety when evaluating a clinical trial; thus we hope that the informed consent language and process ensure that patients have a realistic expectation of how their safety will be monitored.
An overview of the project can be seen here (paper in progress).
In conclusion, we thank you again for the opportunity to comment. We applaud your efforts and look forward to working with OHRP as appropriate to develop and implement the final rule.