Identification and Re-consent of Existing Cord Blood Donors for Creation of Induced Pluripotent Stem Cell Lines for Potential Clinical Applications
Keren M Abberton, Tricia L McDonald, Mary Diviney, Rhonda Holdsworth, Stephen Leslie, Martin B Delatycki, Lin Liu, Guy Klamer, Phillip Johnson, Ngaire J Elwood
Stem Cells Translational Medicine, 8 September 2022
Abstract
We aim to create a bank of clinical grade cord blood-derived induced pluripotent stem cell lines in order to facilitate clinical research leading to the development of new cellular therapies. Here we present a clear pathway toward the creation of such a resource, within a strong quality framework, and with the appropriate regulatory, government and ethics approvals, along with a dynamic follow-up and re-consent process of cord blood donors from the public BMDI Cord Blood Bank. Interrogation of the cord blood bank inventory and next generation sequencing was used to identify and confirm 18 donors with suitable HLA homozygous haplotypes. Regulatory challenges that may affect global acceptance of the cell lines, along with the quality standards required to operate as part of a global network, are being met by working in collaboration with bodies such as the International Stem Cell Banking Initiative (ISCBI) and the Global Alliance for iPSC Therapies (GAiT). Ethics approval was granted by an Institutional Human Research Ethics Committee, and government approval has been obtained to use banked cord blood for this purpose. New issues of whole-genome sequencing and the relevant donor safeguards and protections were considered with input from clinical genetics services, including the rights and information flow to donors, and commercialization aspects. The success of these processes has confirmed feasibility and utility of using banked cord blood to produce clinical-grade iPSC lines for potential cellular therapies.

Editor’s note: BMDI Cord Blood Bank is one of three public cord blood banks in Australia, which form the AusCord network.

Informed Consent for Placebo-Controlled Trials: Do Ethics and Science Conflict?
Hope A. Feldman, James A. Feldman, Charles C. Miller, Garrett Walsh, Jon E. Tyson
Ethics & Human Research, 1 September 2022
Abstract
The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled trials, and we explore the fundamental ethical and scientific complexities involved with each.

An Expanded Role for IRBs in the Oversight of Research Biopsies
Laura A. Levit, Julie Kaneshiro, Jeffrey Peppercorn, Mark J. Ratain
Ethics & Human Research, 1 September 2022
Abstract
Research biopsies included in cancer clinical trials have the goal of advancing scientific understanding of the biological bases of cancer and its treatments, but may offer no prospect of direct benefit to participants and often pose more than minimal risk. The research community is examining the ethics of research biopsies increasingly often, especially when they are mandatory for study participation but do not support primary study objectives and thus are “nonintegral” to the study. Ethical concerns center on the limited scientific justification supporting some biopsies, risks to research participants, and the potential for coercion and therapeutic misconception during the informed consent process. There is also a lack of comprehensive oversight of research biopsies by regulatory agencies and institutions. This paper reviews these ethical concerns, discusses the scope of federal oversight, and suggests that institutional review boards (IRBs) should assume a larger role in ensuring the ethical conduct of research biopsies. It concludes with guidance to IRBs on how to weigh the risks, benefits, and acceptability of such biopsies in different contexts that is based on a framework the American Society of Clinical Oncology developed for the inclusion of research biopsies in oncology clinical trials.

Initial Steps in Creating a Patient-Centric Addendum to Clinical Trial Informed Consent Forms
King-Kallimanis, A. Ferris, L. Dropkin, M. Molina, L. Redway, U. Basu Roy
Journal of Thoracic Oncology, September 2022; 17(9) pp S71-S72
Abstract
Introduction
The purpose of the informed consent form (ICF) is to outline risks and benefits of an interventional clinical trial to a patient. In reality, most ICFs are written using scientific jargon, are long, and include extraneous information not pertinent to the patient (e.g., legalities of trial participation). Using lung cancer as a case study, we are conducting a multi-step project involving patients and caregivers, trialists, regulators, and clinical trial sponsors to streamline the informed consent process by creating a 1-2 page template addendum to the ICF summarizing key points relevant to patients.
Methods
Step 1 included an audit of 20 ICFs guided by 45 CFR 46, HHS regulations for the protection of human subjects in research, which requires the ICF to explain elements like which procedures are experimental. Step 2 included focus groups and in-depth interviews with patients with lung cancer (n=9) to learn what information was critical when considering a hypothetical ICF. In this abstract key, findings from steps 1/2 are summarized. Additional steps are planned to reach our final outcome.
Results
The 20 ICFs reviewed were from phases 1, 2, and 3, expanded access and single patient trials covering predominantly non-small cell lung cancer and 60% were global trials. Average length of the ICFs was 21 (range 15-34) pages and most required CFR topics were covered. “What would happen if the trial failed” was least often covered (14 of 20). Average reading level was 10th grade, whereas average US reading level is 8th grade. Readability varied by section, “the purpose of the study” section had the highest reading level (11.5). In the qualitative research component (step 2), all participants were “overwhelmed” by the hypothetical ICF. When asked the intent of the forms, one participant noted “to cover their butts”. The idea of an addendum that provides a summary with reference to page numbers in the ICF for more details was well received. Participants were asked to list information they wanted included in the addendum (table). Suggestions broadly map to HHS regulations.
Conclusions
While ICFs place greatest emphasis on trial procedures and risks, variations in ICF architecture and readability mean it is difficult for patients to make an informed decision to participate in a clinical trial. Our study implications extend beyond lung cancer, highlighting key areas for improvements to the ICFs and providing a clear roadmap for developing a patient-centric addendum for ICFs in all cancer clinical trials.