Limits on Risk and Burden

Part of Pediatric Trials: The extra protections children get.

About 3 minutes. Free, in your language, no account needed.

This is general education about clinical research — not medical advice, and not a way to join a study. Talk to your own doctor about your situation.

Adults may consent to considerable risk on their own behalf. Children cannot consent at all, so someone else has to set limits for them.

The ICH E11(R1) Addendum sets those limits out. They are stricter than many parents expect, and they are worth knowing.

The starting position

Children should not be enrolled in a study unless it is necessary to achieve an important pediatric public health need.

Where studies are needed, they should be conducted in children who have the disease or condition the product is intended for, unless an exception is justified.

The rule when there is no prospect of benefit to the child

Some study procedures are done purely to gather knowledge, with no expectation of helping the child in front of you.

For those, the Addendum states that the foreseeable risks and burdens must be low — comparable to the risks and burdens a child would meet in their routine clinical care. And it adds that the burden of trial-related activities should be minimized.

The plain version: research that will not help this child should not ask more of them than an ordinary day of their care already does.

The rule when risk is greater than low

If an intervention or procedure presents more than low risk, the Addendum states it must offer a sufficient prospect of clinical benefit to justify or outweigh exposing children to that risk.

It goes further. The balance of risk and expected benefit must be at least comparable to the available alternative treatments, so that the child is not disadvantaged by taking part.

That last clause is the one to remember. It is a written expectation that being in a study should not leave a child worse off than the alternatives available to them.

And the knowledge has to be worth something

The Addendum adds that there should be a reasonable expectation that the knowledge resulting from the study will contribute to the health of the pediatric population.

A study that would produce nothing useful cannot justify asking children for anything at all.

Fewer children, fewer procedures

ICH E11 requires that studies minimize the number of participants and the number of procedures, consistent with good study design, and that mechanisms exist to stop a study quickly if an unexpected hazard appears.

There is also a rule against using children unnecessarily: information that could be obtained in a less vulnerable, consenting population should not instead be obtained from a more vulnerable one.

Questions this gives you

These limits turn into things you can ask about a specific study:

• Which parts of this are expected to help my child, and which are only to gather information?
• For the parts that will not help my child, how do the risks compare with an ordinary day of their care?
• Why does this question need to be answered in children rather than adults?
• How many procedures does this add, and is each one necessary?
• What would stop this study early?

In short

• Children should not be enrolled unless it is necessary for an important pediatric health need.
• Procedures with no prospect of benefit to the child must carry low risk, comparable to routine care, with burden minimized.
• Anything above low risk must offer enough prospect of benefit, and the balance must be at least as good as the available alternatives, so the child is not disadvantaged by taking part.
• The knowledge produced must be reasonably expected to help children generally.
• Studies must use the fewest children and procedures possible, and be stoppable quickly if a hazard appears.