The main objective of risk management and minimization assessment is tailored in protecting subject’s well-being, welfare and privacy, in clinical studies. Thus, it is important to understand that investigational medicinal products have some inherent risks. Therefore, the risks could be minimized or maximized based on the design of the clinical trial in question. A well thought out and thorough clinical protocol focuses on minimizing the risk-aspect of a clinical trial while maximizing the benefits. Hence, a well-designed study for a quality medicinal product is the safest risk-assessment application in implementing effective medical interventions for any disease or condition in order to achieve the best clinical outcome (VanDen Bos, 2007). The risk-benefit assessment study must address specific research questions with a clear and precise answers to the claims originally put forward in the study. The precision of research questions narrow down the inclusion/exclusion criteria such that not too many parameters would be inserted in the subject’s enrollment process, which can cause a statistical error by selecting subjects outside the criteria parameters. Hence, selecting the wrong human-subjects may not only subject the whole participating human-subjects in jeopardy but it exposes the subjects to unwanted risks and harms.

In cases where the inclusion/exclusion criteria needs modification, preferably and when possible, it is less complicating to modifying the inclusion/exclusion criteria while the institutional review board (IRB) is still reviewing the study protocol than when the study protocol has been approved by the IRB or when the trial enrollment or study had begun. However, principle investigators (PIs) may choose to modify the inclusion/exclusion criteria during a clinical trial when for instance, the research question is too broad to address the issue being tested or obtain a sound scientific conclusion. Furthermore, the PIs have the discretion to modify the inclusion criteria when the study risks outweighs the benefits for the individual subjects participating in research, or the study design itself poses serious adverse events on the subjects (Shamoo, 2006).

Most importantly, when subjects are expose to risky procedures with allergic reactions or adverse events, the situation should be addressed urgently to ensure subjects’ safety and well-being. Perhaps, the situation or the urgency to the situation may require revision of the study protocol and safety amendments in order to ensure that the study subjects are not in further health risk. Furthermore, the inclusion/exclusion criteria may be amended to avoid undue influence or corruption of judgment if the inclusion/exclusion criteria are targeting vulnerable human subjects. According to the official IRB guidebook on the guideline for inclusion/exclusion incentive/reward conditions, incentives may be termed coercion or corruption of judgment if is it too attractive to blind potential or prospective subjects to the potential risk and harm inherent in research or impair their better judgment (HHS, 2012, Grady, 2005).

In a situation whereby the risks an individual participant bears outweighs the benefits in any phase of clinical study, it is only appropriate to continue the trial if the subjects are not subjected to life threatening situation and if there is a valid scientific benefit to the society (Shamoo, 2006). In addition, if there is coercion in the enrollment process of subjects and the risk is too high for the subjects enrolled in a clinical trial, then the situation bears enough ethical qualms to induce an ethical conscious PI to stop the clinical trial. Nonetheless, even if the subjects meet the inclusion/exclusion criteria and there is enough evidence to show that subjects’ lives are threatened and are exposed to serious adverse events, the study conditions is enough evidence to stop the study.

References

Grady, C. (2005).  Payment of clinical research subjects. J Clin Invest. 2005; 115(7):1681–1687 doi:10.1172/JCI25694. Retrieve from http://www.jci.org/articles/view/25694/pdf.

Grant, R., & Sugarman, J. (2004).  Ethics in human research. Do incentives matter? JMP, 29(6), 717-738. Retrieve from http://www.waisman.wisc.edu/events/ethics/sprin06-sem2-incentives-compensation.pdf.

Health and Human Services. (2012). Institutional Review Board Guidebook. Retrieve from http://www.hhs.gov/ohrp/archive/irb/irb_chapter3.htm.

Nelson, R.M. (1998). Children as research subjects. In: J.P. Kahn, A.M. Mastroianni, and

J. Sugarman (Eds.), Beyond consent: Seeking justice in research (pp. 47–66). New York:

Oxford University Press.

PDUFA III Risk Management Working Group with members from CDER and CBER. (2005). Guidance for industry: Development and use of risk minimization action plans. Retrieved from http://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0188-gdl0002.pdf

Shamoo, A., & Resnik, D. (2006). Strategies to minimize risks and exploitation in phase one trials on healthy subjects. American Journal of Bioethics, 6(3), W1–W13. Retrieved from http://ezp.waldenulibrary.org/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=a9h&AN=21011099&site=ehost-live&scope=site

Van Den Bos, J. (2007). Inclusion/exclusion criteria in clinical trials. Milliman Pharmaco-Actuarial Advisor. Retrieved from http://publications.milliman.com/periodicals/ pa/pdfs/inclusion-exclusion-criteria-clinical-PA04-30-07.pdf.