One would think that the first revision of the Common Rule since 1991,common rule 1 protecting human research subjects, would allow widespread and detailed input to be certain that vulnerable subjects in resource poor countries are protected from exploitation. Comments on the rule were solicited in the Federal Register Vol 80 No 173 Sept 8, 2015 to modernize, strengthen and increase the effectiveness of the Federal Policy for the Protection of Human Subjects. Based on my experience it wasn’t easy to publish my comments. I suspect individuals from income poor countries will have it worse.

I would like to think it wasn’t deliberate but when I first heard about the proposed revisions to the Common Rule it was a result of a chance reading of an article in the medical journal Lancet. When I went to the US government site to learn more about it and to see if I could submit my comments on behalf of vulnerable populations in income poor countries, the deadline for comments was less than a week away. I had important comments that needed to be made as illustrated by any one of the articles on this blog site. Sadly, my experience helped me to understand the virtual impossibility of someone from an income poor country providing any meaningful input.

To begin with, the federal register contained over 125 pages of proposed changes and discussion which were difficult to follow. When I finally completed my comments and attempted to transfer them to the US government website as instructed in the Federal Register a screen popped up stating that the website was down for maintenance. To meet the deadline I stayed up late at night until the website was finally available only to find that comments were limited to 5,000 characters. 5000 characters! I had compiled a list of concerns that total over 5,000 words outlining what was needed to protect vulnerable individuals in income poor countries from research exploitation. The irony was obvious. One of the greatest issues in preventing exploitation is the inability of research subjects and/or their advocates to gain access to regulatory agencies responsible for protecting them. Billions of dollars are spent on clinical research in income poor countries and millions of individuals become research subjects. Many receive no benefit for their participation and many place their lives and the lives of their family at risk for the benefit of others.

What I had experienced was an exclusion of a detailed explanation of my concerns on behalf of individuals in income poor countries. One of my major suggestions on revising the Common Rule was to require representation by vulnerable individuals and/or their advocates on ethical review and research approval committees to correct this deficiency. The disproportionate representation and access to the research approval process by large organizations treads on ethical issues of beneficence.

It took me several hours to reduce my comments to a mere 5,000 characters from over 5,000 words. When I pressed the send button I failed to have confidence that my comments on behalf of vulnerable research subjects would influence the process of revising the Common Rule for the protection of human subjects. But I did understand the virtual futility of someone from an income poor country attempting to provide their comments on issues that affected their welfare.

Below are my abbreviated comments on the Federal Policy for the Protection of Human Subjects. Federal Register Vol 80, No 173 September 8, 2015.

http://www.hhs.gov/ohrp/humansubjects/commonrule/. The full comments will be published in a subsequent blog.

Abbreviated comments on The Common Rule for Protection of Research Subjects.

1) An additional independent IRB should be constructed with greater public representation to review research protocols involving vulnerable subjects in income poor countries to prevent exploitation. 2) A review mechanism for accessible and definitive decision making on research violations must be established to adjudicate ethical and scientific issues raised by interested parties.

Specifics:

Informed consent: Many informed consents lack the basic elements required to maintain ethical standards of research. The description of risks is confined to adverse events. Risk related to omission of adequate treatment should be included e.g. progression of disease and death.

Redress: The specifics of redress were not adequately addressed. http://ethicsinhealth.org/

Benefit to mankind (greater good): this is a concept that is not inherent in most cultures in income poor countries. Asking individuals who are vulnerable to accept the burden of clinical research for the “common good” without benefit is exploitative and violates issues of justice and beneficence. Issues of equity exist when researchers obtain benefits from conducting research but the research participants do not.

Posting of informed consents: who is responsible, who would receive the posting; how do individuals access the informed consents before a study begins? Who is ultimately responsible for providing reviews that are free of conflict of interest including outside review?

Public review of scientific, ethical, and legal issues: the inability of advocates and the public to obtain responses to issues related to the conduct of clinical research is of deep concern. Non-responsiveness and dismissal of concerns by entities established to protect human subjects is frequent.  http://ethicsinhealth.org/

IRB expertise and representation: the proposed composition of IRBs does not adequately address the issue of representation and expertise for studies in income poor countries. The demand for conducting research in income poor countries exceeds both the capacity and expertise of current IRBs. A mechanism must be found to ensure that the expertise of members of the IRB is adequate to understand the science and ethics of each protocol especially those conducted in income poor countries.

Conflict of interest: personal and institutional benefits are significant. With the cost of the research studies exceeding millions of dollars per study a means of defining conflict of interest in review and approval of research studies is necessary.

Exploitation: the definition of vulnerable subjects and exploitation requires greater precision. Research in vulnerable populations that does not provide direct benefits should be considered exploitation. The increasing recruitment of individuals in income poor countries because they are more readily available, more easily enrolled, result in less expensive research, and the ability to manipulate ethical guidelines and allow inferior standards of care must be carefully scrutinized.

Application of the Common Rule: The common rule should be applied to all clinical research conducted by individuals regardless of their institutional affiliation or source of funding. We have identified clinical research studies of questionable ethics and science that have been conducted in income poor countries by US academic institutions on products that have not been approved by the FDA. We have also encountered examples of clinical research that would be considered unethical in the US but were conducted in income poor countries utilizing children. Following our objections, we were informed that US guidelines do not apply and that there is no oversight once funds are awarded.