This posting is the fourth of a six-part series that will explore various real-life examples of IRB Forum Shopping experienced by Veritas IRB over the past year. Our first posting provided an introduction to this topic.

In December 2015, a Canadian research sponsor submitted a Phase III, multicenter study to Veritas IRB for review. It involved women, 45 years of age and over. Veritas IRB approved the study with the condition that women of child-bearing potential must undergo routine urine pregnancy testing during their participation in the study and upon exiting the study, in addition to the baseline testing.

Instead of complying with the condition, the research sponsor threatened to withdraw its submission and seek approval from another IRB in Canada unless Veritas IRB removed its requirement for pregnancy testing. Veritas IRB upheld its condition and the research sponsor made good on its threat.

Why did Veritas IRB request pregnancy testing in the first place? Although the fertility potential of the female study population was expected to be low, the possibility of pregnancy existed.

As per the Investigator’s Brochure, the effects of the investigational drug on the embryo/fetus in two animal species were cleft palate, craniofacial abnormalities, reduced fetal weight, and skeletal growth retardation.

The study protocol excluded pregnant women from entering the study as evidenced by a urine pregnancy test, however, it failed to monitor pregnancy during the study.

Interestingly, the study protocol clearly instructed investigators on what to do in the event of a pregnancy; immediately terminate study participation and report the event to the research sponsor, counsel the research participant, monitor the pregnancy until its conclusion, etc. – but it did not provide the investigator with the tools to assess pregnancy and reduce exposure of the embryo/fetus to the investigational drug.

Sadly, this study is currently being conducted in 25 Canadian centers. It is anticipated that 250 research participants will be enrolled into this study.

When one considers only the research participants of child-bearing potential in this study, implementing the condition of pregnancy testing would have cost the research sponsor, at most, CAD 500.00. It is interesting to note that the research sponsor probably paid upwards of CAD 2,000.00 to have the study reviewed by another Canadian IRB!

While on the topic of costs, what is the emotional cost to the woman who finds out she is pregnant after taking an investigational drug that may have harmed her unborn child? What are the personal, familial and societal costs involved in raising a child or caring for an adult with a congenital abnormality?

In Canada, the Declaration of Helsinki, ICH-GCP Guidelines and the TCPS require that investigators and IRBs ensure that all foreseeable risks to participants are appropriately minimized. An accredited IRB operating in Canada must comply with these guidelines order to maintain its accreditation!

This case highlights IRB Forum Shopping by the research sponsor – the research sponsor felt that the condition placed on the study by the IRB was “negotiable” – that it could use the threat of IRB Forum Shopping in order to gain approval by the IRB.

This would not have been possible had standards been applied in a uniform manner by all private IRBs.

About the Authors

Martin Letendre

Martin Letendre is responsible for managing Veritas IRB's business operations and administering the activities of the Veritas IRB Boards. Martin is a member of the Quebec Bar and brings more than a decade of experience in health law and research ethics. His expert knowledge of, and ongoing activity and interest in research ethics have led to the publication of several reports and articles in peer-reviewed journals, and invitations as guest speaker at numerous conferences and scientific meetings. Martin was actively involved in the creation of an on-line tutorial for institutional research ethics boards in Quebec and was a member of Canada's three federal research agencies' Panel on Responsible Conduct of Research.

Janice E. Parente

Janice completed both her PhD and Post-Doctoral Fellowship in Molecular Pharmacology, and proceeded to develop her skills at the Director level within global pharma before founding her first contract research organization (CRO) in 1992. During the ensuing decade, Janice established her credentials as a successful and respected business leader and entrepreneur. In 2002, she sold her company in order to found ethica Clinical Research Inc., instilling in it her values and commitment to the protection of human research participants. This commitment led to ethica becoming the first Canadian entity and the first CRO in the world to earn full accreditation of its Human Research Protection Program (HRPP) in 2006. Janice's leadership and entrepreneurship have been recognized through numerous awards and nominations such as the prestigious Ernst & Young and Bank of Montreal Entrepreneur of the Year Awards and PROFIT Magazine's PROFIT W100 ranking of Canada's Top Women Entrepreneurs.
The Veritas IRB Inc. Editorial Board

The Veritas IRB Editorial Board covers questions of research ethics, clinical trial conduct, and human research participant protection primarily for sponsors, CROs and investigators/researchers. // Le blogue de Veritas IRB aborde des questions de l'éthique de la recherche, de la bonne conduite des essais cliniques, et de la protection des participants à la recherche dans une perspective axée sur les promoteurs de la recherche, les organismes de recherche sous contrat (ORCs ou CROs), et les chercheurs.