HOW TO PRINT To print this page, use your browser's print button. To print the entire document, download the PDF or click here and use your browser's print button. SAMPLE LANGUAGE Sample 1 - Dose Escalation Design Sample 2 - Randomization to Experimental or Control Arm TOOLS & BACKGROUND MATERIALS Simplification Guide to Medical Terms
MAIN POINTS The consent form should: Describe the study procedures and timeline for these procedures Distinguish between the research component and standard treatment Potential participants should be told how they and others will be assigned to study cohorts and, if applicable, their dose level.

NIH GUIDELINES: "The subjects should be provided with a detailed explanation in non-technical language of the purpose of the study and the procedures associated with the conduct of the proposed study, including a description of the gene transfer component."

DISCUSSION
Potential participants should be provided a description of the design of the study, including a schedule of the study events and expected time commitments. The language in the procedure section of the consent form should not be overly scientific so that average lay readers can understand what they will experience as research participants. Breaking the procedures down into stages may make the information easier to understand. Timelines, including those presented in tabular or graphical format, may also be helpful.

Whenever applicable, the consent form and process should attempt to make clear to potential participants how research participation differs from being treated for health problems outside of the context of the study. This topic is also addressed in the Alternatives section.

Organization of Procedures Section: It is especially important in early-phase research, such as most gene transfer studies, to distinguish standard treatments from investigational interventions, and tests and measurements provided as part of clinical care from those related to the research study. Institutional review boards (IRBs) and institutional biosafety committees (IBCs) can provide guidance on how to differentiate between these activities. Using separate consent forms, or separate consent form sections, for the research component and standard treatment component is one reasonable way to distinguish between the two.

Avoiding Improper Language: Because gene transfer interventions, like other investigational interventions in early-phase trials, are unproven and have not yet been studied for efficacy, they should not be referred to as treatments.

Some examples of improper language are:

• You will receive up to three treatments in this study.
• Your participation in this treatment program is entirely voluntary.
• Your illness will be treated using gene transfer.

Alternative language reinforcing the experimental character of gene transfer should be chosen appropriately for a given protocol. Possible alternatives to the above examples might be:

• Participants will get up to three gene transfer infusions in this study.
• Your participation in this research program is entirely voluntary.
• As part of this study, you will get a gene transfer injection.

Dosing Group Designs and Cohort Assignments: Many Phase I studies utilize dose escalation to determine a safe gene transfer agent dosage amount. If the study involves dose escalation, the investigator should explicitly state to which dosage cohort the potential participant will be assigned, the dose level to be received, and any potential risk-benefit balance for that particular cohort. In providing this information, the investigator should describe and explain dose escalation designs for the following reasons:

• Potential participants should be told that the dose level selected for them is not based on a medical determination of what is best for their treatment; instead, the dose level is based on the order in which they enrolled in the study and/or how previous participants have reacted. During enrollment, they should be told about the experience of earlier enrollees when possible.
• The risks of harm and discomfort from the experimental intervention probably bear some relationship to the dose level. Potential participants should be informed that any adverse reactions might be worse at higher doses.
• The potential for direct benefit, if any, may also vary with the dose level. Potential participants should be informed that any likelihood or amount of benefit might be different at different doses.

Other Study Designs: Many Phase III studies involve such features as randomization, inclusion of control groups, use of placebos, and blinding. All of these features should be explained simply and clearly in the consent form and process. Double-blind design explanations should include the information that the blind may be broken if necessary to protect the participant's health and welfare. IRBs and IBCs can provide guidance and sample language on blinding and randomization.

Procedures Language: In order to simplify consent forms, researchers are encouraged to consult resources like the Simplification Guide to Medical Terms that suggest replacements for terms that are difficult to understand and, thus, require explanation or substitution. In addition, dosage information should be as precise as possible; terms like low, medium, or high dose should be quantified in terms that are most informative to potential participants.

SAMPLE LANGUAGE

Sample 1 - Dose Escalation Design

We do not know the highest dose of the gene transfer agent that is safe. To find out we will give the gene transfer agent to [number] participants at one dose level. If that is safe we will raise the dose given to the next group of participants. The dose you will get will depend on how many participants get the agent before you and how they react. The investigator will tell you this information. This will help you think about possible harms and benefits. Since the gene transfer intervention is experimental, what is likely to happen at any dose is not known.

Sample 2 - Randomization to Experimental or Control Arm

It is not clear whether experimental gene transfer will be more effective than standard treatment. For this reason, you will be randomly assigned (like the flip of a coin) to one of two groups: the experimental group (gene transfer) or control group (standard treatment). You will have a 50% chance of being assigned to either group.