Tag: clinical investigators

Bioethics Blogs

The 2017 Common Rule and the Clinical Ethics of Prolixity

Some bioethicists link the beginnings of our field to the Nazi Medical experiments and the Nuremberg Trial (Annas). Whether this is the beginning of bioethics is debatable, but without a doubt, research ethics has been a central topic in the field. In fact, the very first federal bioethics commission laid out the principles of research ethics in the Belmont Report. Later, the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research recommended to the President and Congress that a uniform framework and set of regulations should govern human subjects research.  This effort reached fruition under The Federal Policy for the Protection of Human Subjects or the “Common Rule” that was issued in 1991.  Since then, there have been no major changes to the regulations – until now.  After a five-year process and thousands of comments, the new “final rule” was released on January 19th, 2017.  The July 2017 issue of the American Journal of Bioethics addresses these changes.  In addition to our usual open peer commentaries, we are posting a number of blog posts written in response to the AJOB target article.

The following is a re-post of Steven Mile’s original February 2017 post.


by Steven H. Miles, MD

The new Common Rule to protect human subjects has an extraordinarily large and diverse audience.[i] The new Rules defines the obligations of an enormous number of personnel at the National Institutes of Health as well as virtually any other government agency engaged in research with human subjects. The Rules define the requisite knowledge, training, and work of staff who oversee and conduct clinical research in the United States.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

REGISTER NOW (2/10)! Returning Results to Research Participants: A Health Policy and Bioethics Consortium

REGISTER NOW! Returning Results to Research Participants: A Health Policy and Bioethics Consortium February 10, 2017 12:30 – 2:00 PM Wasserstein Hall, Milstein East C (2036) Harvard Law School, Cambridge, MA Register Now! Clinical investigators, public health advocates, and IRBs … Continue reading

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Balancing the Evidence: Animal efficacy studies should have more weight in the risk/benefit calculus ahead of clinical trials

Clinicians, sponsors, ethics review committees, and others are charged with ensuring that risk is in a favourable balance with benefit when patients enrol in trials. Yet how do they make this judgment, when the only evidence available is from preclinical animal studies?

In our recent article published in the Journal of Medical Ethics1, we offer an answer to this question. We argue, first, that review committees and clinicians should evaluate the clinical promise of a new intervention based on preclinical efficacy evidence. Specifically, they should form judgments about the clinical promise of a new intervention based on how well preclinical studies address common threats to clinical generalization. Second, review committees should adjust their estimates of clinical promise based on clinical trials with related drugs (e.g. within the same class of agents). All else being equal, the stronger the clinical promise, the stronger the moral justification for embarking on an early-phase clinical trial.

Before consuming scarce financial and human resources, including exposing volunteers and patients to potentially ineffective treatments in trials, researchers should capitalize on the knowledge gained from animal efficacy studies. Ethics review committees and clinical investigators will likely protest they lack the expertise, skill or time to evaluate preclinical evidence. Or, that drug regulators like FDA already make such judgments.

However, the FDA itself states that “lack of… potential effectiveness information should not generally be a reason for a Phase 1 IND to be placed on clinical hold2,” and it explicitly delegates judgments about risk/benefit to IRBs3. This means that, if ethics reviewers and investigators really do lack the expertise, skill or time to review preclinical evidence- they are surrendering their mandate to protect patients from undue risk in early phase trials.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Predicting Risk, Benefit, and Success in Research

The task set before clinical investigators is not easy. They are supposed to answer pressing scientific questions, using very few resources, and exposing patient-subjects to as little risk as possible. In other words, we expect them to be rigorous scientists, stewards of the medical research enterprise, and guardians of their patients’ interests all at the same time. While the duties that emerge from these various roles are sometimes orthogonal, they are intersecting and aligned at the point of clinical trial design. Insofar as a trial is well-designed–meaning that it is likely to answer its scientific question, make efficient use of research resources, and minimize risk–the investigator has successfully discharged all of these duties.What is more, there is a common activity underlying all of these requirements of good trial design: Prediction. When investigators design studies, they are making an array of predictions about what they think will happen. When they decide which interventions to compare in a randomized trial, they are making predictions about risk/benefit balance. When they power a study, they are making a prediction about treatment effect sizes. The accuracy of these predictions can mean the difference between an informative or an uninformative outcome–a safe or unsafe study.

The importance of these predictions is already implicitly recognized in many research ethics policies. Indeed, research policies often include requirements that studies should be based on a systematic evaluation of the available evidence. These requirements are really just another way of saying that the predictions underlying a study should be as accurate as possible given the state of available knowledge.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Fordham RETI Fellow Tackles HIV Prevention in India through Research & Clinical Practice

Dr. Arunansu Talukdar

Fordham University HIV and Drug Abuse Prevention Research Ethics Training Institute (RETI) Fellow Dr. Arunansu Talukdar is not just conducting research on HIV prevention – as a physician, he is practicing it as well.

Talukdar is a member of the fourth cohort of RETI fellows, and was the 2014 recipient of the Fordham University Center for Ethics Education / Santander Universities International Scholarship, which covers the cost of his travel to Fordham for two consecutive summer training institutes, as well as the cost of his mentored research project (MRP). His MRP examines voluntariness of consent to research involving women participating at a clinic-based HIV intervention trial in Kolkata, India.

In his MRP, Talukdar aims to assess the voluntariness of consent to research for women in a clinic-based research project; identify correlates of voluntariness; and examine whether any anticipated threats/fears/pressures influence the decision of whether to participate in the research project.

Typically, the informed consent process assumes that an participant involved makes the decision of whether or not to take part in a research project. However, in many cultures, important decisions are made by other family or community members, or are made collectively. While these decision-making processes reflect community norms, they are in direct conflict with the autonomy of potential research participants that is embedded in the informed consent process.  Dr. Lloyd Goldsamt of New York University is mentoring Talukdar’s project.

Both a practicing physician and an associate professor of medicine, Talukdar has experience in both academic and clinical settings. After years of working as a physician and caring for patients with AIDS, he obtained a Ph.D.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

PRIM&R’s Response to the FDA’s Draft Guidance on Informed Consent

by Avery Avrakotos, Education and Policy Manager

PRIM&R has long been committed to the protection of the rights and welfare of human subjects, and strongly believes that informed consent is an essential mechanism for providing potential subjects with the information they need to make considered, autonomous decisions about research participation.

In July, the US Food and Drug Administration (FDA) announced it was seeking comment on a draft guidance document titled “Informed Consent Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors.” The draft is a substantial revision to the FDA’s prior guidance on this topic, which was issued by the agency in September 1998. Yesterday, PRIM&R’s Public Policy Committee, which is composed of experts from a wide range of disciplines and institutional settings, responded to the agency’s request with a set of comments on the draft guidance.

In its response, PRIM&R commends the FDA for encouraging investigators to think of informed consent as not simply a form, but rather a dynamic process that can be adapted to reflect the unique needs of potential subjects, as well as local context. PRIM&R also thanks the FDA for its efforts to harmonize regulatory requirements and guidance for human subjects research put forward by the Department of Health and Human Services, the Office for Human Research Protections, and the FDA. PRIM&R’s comments also applaud the addition of expanded sections on informed consent with respect to vulnerable populations and the agency’s consideration of the use of new technologies for obtaining informed consent.

PRIM&R comments also identify several areas where further guidance could benefit IRBs, investigators, sponsors, and, ultimately, subjects:

The Consent Form Versus the Consent Process
In a recent blog post, PRIM&R’s executive director, Elisa A.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Consent and the Autonomy of Human Subjects

by Elisa A. Hurley, PhD, Executive Director

We all know that designing a mechanism for obtaining valid informed consent is a perennial challenge, but it seems to be receiving special and renewed interest lately.

The United States Food and Drug Administration (FDA) recently released a draft guidance, Informed Consent Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors, for public comment. The draft is intended to replace the FDA’s previous, and much briefer, guidance on informed consent, which dates from 1998. Throughout the new draft guidance, the FDA emphasizes that informed consent involves more than a form, and encourages investigators, IRBs, and sponsors to think of informed consent as a dynamic process that can be adapted to reflect the unique needs of potential subjects, as well as local context.

The introduction to the FDA draft states it plainly:

“To many, the term informed consent is mistakenly viewed as synonymous with obtaining a subject’s signature on the consent form. FDA believes that obtaining a subject’s oral or written informed consent is only part of the consent process. Informed consent involves providing a potential subject with adequate information to allow for an informed decision about participation in the clinical investigation, facilitating the potential subject’s comprehension of the information, providing adequate opportunity for the potential subject to ask questions and to consider whether to participate, obtaining the potential subject’s voluntary agreement to participate, and continuing to provide information as the clinical investigation progresses or as the subject or situation requires. To be effective, the process must provide sufficient opportunity for the subject to consider whether to participate.”

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.