|NIH Guidance on Informed Consent
For Gene Transfer Research
Possible Risks, Discomforts, and Side Effects
NIH GUIDELINES: "There should be clear itemization in the Informed Consent document of types of adverse experiences, their relative severity, and their expected frequencies. For consistency, the following definitions are suggested: side effects that are listed as mild should be ones which do not require a therapeutic intervention; moderate side effects require an intervention; and severe side effects are potentially fatal or life-threatening, disabling, or require prolonged hospitalization. If verbal descriptors (e.g. 'rare,' 'uncommon,' or 'frequent') are used to express quantitative information regarding risk, these terms should be explained. The Informed Consent document should provide information regarding the approximate number of people who have previously received the genetic material under study. It is necessary to warn potential subjects that, for genetic materials previously used in relatively few or no humans, unforeseen risks are possible, including ones that could be severe. The Informed Consent document should indicate any possible adverse medical consequences that may occur if the subjects withdraw from the study once the study has started."
Bulleted lists of clearly defined items with a brief explanation of what the risk or side effect may entail may be helpful way to present the risks of harm in the consent form.
Since some risks of harm cannot be known with certainty, it is always helpful to discuss what is uncertain and unknown.
Differences in Risk of Harm for Phase I, II, III Studies: The available evidence about risks of harm and potential discomforts of a gene transfer intervention differ according to the phase of the study. Risk discussions should be phase-specific. For combined phase I/II studies, it is especially important to distinguish (preferably in separate consent forms) between the risks for harm of each phase.
Sample 1 - Risks Associated with a Study Agent
The vector, which carries the gene into your cells, is considered harmless in humans. However, it is possible that the virus could grow and/or make the cells cancerous. There is a risk that the vector may enter the normal tissue surrounding the tumor, or other sites in the body. Another risk is that the vector might stay in your body and cause cancer or other diseases. Your immune system is expected to reject (kill) the vector in [time amount]. Thus, the vector should not be able to survive and grow in your body. The risk of causing a new cancer is probably very small. Although some vectors have caused cancers, no cancers have yet been found in any of the experiments in which genes have been transferred into monkeys and humans using this vector.
Sample 2 - Risk of Cancer Caused by Gene Transfer
Researchers have wondered whether a transferred gene might sometimes land in a place in a cell where it can cause harm. This happened to two children in another study. After getting the gene transfer, they developed leukemia (a type of blood cell cancer). A group of experts looked at all the test results. They found that gene transfer caused the leukemia by making some cells grow out of control. The children appear to be responding to treatment of the leukemia, but their long-term health is unknown at this time.
There is a risk of unknown size of your child developing cancer, such as leukemia, should you volunteer your child to enter into this experimental study. This is a serious risk because cancers of the blood can lead to death.
Problematic Sample 1
[Gene transfer agent] may cause pain at the injection site. It may also cause some heart toxicity. Patients may also have shortness of breath and/or allergic reactions, including hives, skin rash, difficulty breathing, and/or fever. There may be damage to the liver and kidneys. These reactions could result in death. Having a tumor biopsy may cause air in the chest and/or bleeding to occur. Air in the chest is treated with the insertion of a small tube. A bronchoscopic biopsy (sample of very tiny piece of the mucosa inside the lung) may cause coughing up of blood. This is usually temporary. Severe bleeding requiring emergency treatment such as intubation and thoracotomy could also occur. This clinical research study may involve risks to the participants that are unknown at this time.
Comments: The risks of harm would be clearer if they were ranked according to likelihood and severity. Risks of harm particular to the gene transfer should be included. Also, medical terms like "intubation" and "thoracotomy" need to be described in lay terms.