Vaccinated vs. Unvaccinated Part 4 - The Legal Perspective

This is the final installment of the vaccinated vs. unvaccinated series. If you haven't read the other articles, in part 1 I discussed the general shape of prospective, randomized, placebo-controlled study to answer the question of whether or not vaccines play a causative role in autism. In part 2, I provided an overview of the history of ethics in medical research, particularly discussing three key documents: the Nuremberg Code, the Declaration of Helsinki and the Belmont Report. And in part 3, I examined whether or not the study would be ethical. In this post, I will look at whether the study could legally be conducted. Before continuing, please go read the first three parts. The full series can be found here.

The primary reference I'll use for this post is 45 CFR 46, the set of regulations that governs research involving human subjects. In particular, I will refer to subparts B and D (sections 46.201-46.207 and 46.401-46.409), which provides for special protections for research involving newborns and children.

In part 3, I established that our study would be greater than minimal risk. While that does not preclude conducting it, it does mean that certain additional legal requirements must be satisfied before the study can be approved and move forward. I also showed that regardless of legalities, the study would be unethical. Only by some strange, alternate sense of ethics could one argue that it would be okay to go ahead with the study. But, supposing that we live in bizzaro world and the ethics are not a hindrance, could our study be conducted legally? Let's take a look.

First, we need to establish some definitions to determine which regulations would apply. In our study, we are enrolling subjects from the time they are born and following them for at least five years. That means we're dealing with the legal categories of neonates (newborns) and children (those who have not reached the legal age for consent). The neonate category can be further broken down into: viable, uncertain viability and nonviable. As far as the regulations are concerned, "viable" means:

being able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration.

Nonviable means that although the newborn may be living after delivery, they are unable to independently maintain heartbeat and respiration. For our study, we probably do not want to include children that cannot survive without life support. Those of uncertain viability could possibly be included, but that may introduce confounding factors that would skew our results. Even without such confounding, we wouldn't legally be able to include them anyway. According to 45 CFR 46.205(b):

Neonates of uncertain viability. Until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research covered by this subpart unless the following additional conditions have been met:

(1) The IRB determines that:

(i) The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or

(ii) The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research; and

(2) The legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent's legally authorized representative is obtained in accord with subpart A of this part, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

Since the study does not enhance the likelihood of survival of the newborn and viable neonates can be used instead, we cannot enroll neonates of uncertain viability in our study. That makes things a lot simpler, both in terms of legal requirements and scientific validity. Limiting ourselves to viable neonates, we just need to worry about subparts A (general provision) and D (special protections for children).

We'll start with the general provisions in subpart A, specifically 46.111, criteria for IRB approval of research. This bit of regulations outlines some basic requirements before a study involving humans can be approved by an Institutional Review Board (IRB). Specifically, the risks must be minimized and be reasonable in relation to the anticipated benefits/importance of the knowledge expected. Subject selection also needs to be equitable, and informed consent must be obtained and documented for every subject. Finally, for the safety of the subjects, data collection should be monitored, privacy must be protected and, where special populations are considered (e.g., pregnant women or children), additional safeguards must be in place to protect them. Of these, the regulation most likely to sink the study is the one about the risks being reasonable in relation to the expected benefits.

The risks, as mentioned in part 3, involve infection by the diseases prevented by vaccines. Within the timeframe of our study, this includes: hepatitis B, rotavirus, diphtheria, tetanus, pertussis, haemophilus influenzae type B, pneumonia, polio, influenza, measles, mumps, rubella, chicken pox and hepatitis A. All of these have some pretty serious complications, from hospitalization to permanent deafness/blindness to death, at varying levels of risk. Some of these complications can be avoided with high quality medical intervention. Some may occur in spite of intervention. Keep in mind, we are not talking about the increased risk of just one infection, but multiple infections, since the unvaccinated group would not receive any vaccines. The anticipated benefit, if it turns out that vaccines do cause autism, is that they do not get autism. We need to look at which is worse: increased risk of death or serious, permanent injury or increased risk of autism. Autism is a disorder of developmental delay and, given proper intervention and time, is likely to improve in varying degrees depending on the individual. Death and permanent injury do not improve.

Failing to satisfy that required, general provision, the study could not be approved by an IRB. But let's keep going. Let's take a look at the provisions protecting children to see if, even if we made it past the general requirements, the study could be approvable.

Subpart D breaks things down into research involving a) no more than minimal risk, b) greater than minimal risk, but of direct benefit to the individual subjects, c) greater than minimal risk with no direct benefit to the subjects but yielding generalizable knowledge about the subject's disorder or condition or d) research not otherwise approvable but which provides "an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children". We already know that our study is greater than minimal risk, so a) does not apply. Since the purpose of the research is to answer a general question, not to treat a specific disorder that all of the subjects have, there is no prospect of direct benefit to the individual subjects. Thus, b) also does not apply. The study is not examining a condition that the subjects have going into the study, and therefore holds no prospect of producing generalizable knowledge about their condition. C) is out. That leaves us with research that isn't otherwise approvable, but which can give us knowledge about a serious problem that affects children (like autism).

The requirements for the final option state that:

HHS will conduct or fund research that the IRB does not believe meets the requirements of §46.404, §46.405, or §46.406 only if:

(a) the IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children; and

(b) the Secretary, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, education, ethics, law) and following opportunity for public review and comment, has determined either:

(1) that the research in fact satisfies the conditions of §46.404, §46.405, or §46.406, as applicable, or (2) the following:

(i) the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children;

(ii) the research will be conducted in accordance with sound ethical principles;

(iii) adequate provisions are made for soliciting the assent of children and the permission of their parents or guardians, as set forth in §46.408.

Basically, it comes down to convincing both the IRB (or IRBs if multiple sites are involved) and the Secretary of the Department of Health and Human Services that the research can go ahead. Assuming that all the relevant people can be convinced that it is okay to continue, the next step is getting the consent of the parents or guardians. Because of the category under which this study falls, both parents must give consent, with limited exceptions. Needless to say, there are some hurdles involved, convincing all parties involved (while providing full information without distortion to make an informed decision) that the risks posed to the subjects are reasonable.

To sum up, a prospective, randomized, placebo-controlled vaccinated vs. unvaccinated study poses greater than minimal risk to the subjects involved. Several ethical principles would be violated by the study. The regulations governing human subject protections render this study unapprovable, so it would not be able to legally be conducted. For all of these reasons, this study would not be able to be conducted. With this knowledge, it is irrational to demand that such a study be performed.

Thus ends my series on the prospective, double-blind, randomized, placebo-controlled trial. I hope you have found it informative and have gained some understanding of just why it cannot be done, despite the quite concrete answer it would provide. Please comment and share with others.
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Related Posts:
Vaccinated vs. Unvaccinated Part 1 - An RCT Overview
Vaccinated vs. Unvaccinated Part 2 - A History of Medical Research Ethics
Vaccinated vs. Unvaccinated Part 3 - Ethical Evaluation
Complete Vaccinated vs. Unvaccinated Series