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 - Healthy Volunteer Sample 2 - Patient-subject Volunteer Sample 3 - Phase I Sample 4 - Phase I Sample 5 - Phase II Sample 6 - Phase III Problematic Sample 1 TOOLS & BACKGROUND MATERIALS Sample Gene Transfer Descriptions OBA Brochure, "Deciding to Participate in Gene Transfer Research"  NIH Backgrounder on Human Gene Transfer Research Sample Vector Descriptions
MAIN POINTS The purpose statement should: Not overstate the goals of the study Reflect the study phase Include an understandable explanation of gene transfer

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 given a succinct explanation of why they have been approached for the proposed study. In particular, they should be told whether they are being approached because of their disease or as a healthy volunteer ². The purpose section should also include general information about the study design (including phase and objectives), the nature of the disease, and a brief description of the gene transfer intervention.

The greatest challenges to investigators in describing the purpose of the study include:

• Presenting the study and the science of gene transfer in a way that does not imply that the logic driving the hypothesis of the study is fact
• Describing the overall goal of the study in a way that does not imply that the long-term research goals (e.g., finding a new way to treat melanoma) are the goals of the current phase of the study (e.g., to determine a safe dosage)

Placing emphasis on the research nature of the intervention and appropriately qualifying any statements or claims about anticipated outcomes and potential benefits of the current study are as important when describing the purpose as when describing or disclaiming any potential benefits. The purpose section of the consent form should be compared with the potential benefits section to avoid discrepancies and minimize possible confusion.

Study Phase: The purpose description should reflect the phase of the trial and should be based on pre-clinical and other clinical evidence. A brief description of classic study phases, reflecting the design and purpose of each, is included below as a reference. These descriptions could also be modified and adapted to use when informing potential participants.

Phase I studies are small studies of an experimental intervention and are usually the first time the intervention has been tried in humans. Their primary purpose is to test for safety, to see how the intervention affects the body, to test for harms and discomforts, and to see how the side effects change at different doses. Many phase I studies employ dose escalation designs.

Some, but not all, Phase I trials also attempt to reveal whether or not the intervention has any beneficial effects. Any Phase I trials with this additional purpose should be designed and powered appropriately. The hope for therapeutic benefit is not a sufficient basis for identifying efficacy testing as a secondary purpose.

Phase II studies are mid-sized studies of the experimental intervention and are designed to begin a more complete evaluation of the effectiveness of the intervention. The purpose of Phase II studies is to see if the intervention has any beneficial effects at a dose level thought to be safe based on earlier studies. Phase II studies also continue to test for harms, discomforts, and side effects resulting from the intervention.

Phase III studies are large studies of the experimental intervention for the purpose of gathering data on a larger group of participants in order to prove or disprove the safety and effectiveness of the intervention that has been tested in earlier studies. Phase III studies also reconfirm optimal doses and routes of administration. Phase III studies also provide an opportunity for investigators to recognize less-common side effects in a larger number of participants. The experimental intervention in Phase III studies may be compared to a standard treatment or to a placebo.

Relevant aspects of study design linked to phase - such as dose escalation in Phase I trials, and use of placebo groups, control groups, and comparison group designs in Phase III trials - should be briefly mentioned in the purpose section, and then explained in appropriate and relevant detail in the procedures section of the consent form.

Phase I/II Studies: Because investigators should build upon the knowledge gained in Phase I of their study, and so that potential participants considering enrollment in Phase II can benefit from knowing the outcomes of Phase I, it is important that Phase I and Phase II not be combined unnecessarily. The NIH Recombinant DNA Advisory Committee (RAC) reviews many Phase I/II studies and sometimes questions the appropriateness of a combined design. In the event that Phase I and Phase II must be combined, one consent form should be used for the Phase I portion of the trial and a second should be used for the Phase II portion of the trial to allow the different goals of the Phase I and Phase II components to be properly understood. If two separate consent forms are not possible, investigators should consider how potential participants are best informed of the differences between Phase I and Phase II and about the phase to which they will be assigned.

Describing Gene Transfer: A brief description of the gene transfer intervention should be provided to the potential participant. If the investigator's institutional review board approves, it may be desirable to create a scientific appendix to the consent form that briefly explains the scientific theory behind gene transfer and how that theory is to be applied in the current study.

The process of gene transfer is likely to be unfamiliar to most potential participants. Therefore, it is especially important that the investigator clearly and simply explain the gene transfer methodology used in the given study. Sample descriptions of different gene transfer methods are provided in this guidance. It is also important to use terms like "genes" and "DNA", especially if the gene transfer intervention is otherwise described by an acronym or other term that does not itself make an obvious connection to the introduction of new genes or new DNA into the body. Background material about basic genetics and the science of gene transfer research may be beneficial to some potential participants.

Describing Vectors: Most gene transfer requires a vector, often described as a transportation system to deliver the gene. Many descriptions use vivid analogies that compare the vector to a car and the gene to the passenger. For studies using a vector, descriptions of this sort may be helpful to lay readers. For those few studies not using a traditional vector (e.g., naked plasmid DNA), the description should discuss the method of delivery in plain language.

Sample vector descriptions for potential participants are included in this guidance. Investigators should pay particular attention to how adenoviruses are described since they are not just a common cold. Adenovirus can be better described this way: "Adenovirus is a common virus found in human respiratory systems. In its normal state, it can reproduce and cause a respiratory infection. Respiratory illnesses caused by adenovirus infections range from the common cold to pneumonia, croup and bronchitis."

² Although use of healthy volunteers is uncommon in gene transfer research, it is not unknown. Healthy volunteers may be an appropriate population in selected studies.

SAMPLE LANGUAGE

Sample 1 - Healthy Volunteer

You have been asked to join this study as a healthy volunteer. This means that the investigators think that they can learn about a certain disease or condition that other people have from participation of healthy people like you.

Sample 2 - Patient-Subject Volunteer

You were asked to be in this study to help the investigators learn more about the type of disease you have. The investigators will try to keep the risks of harm to you from being in the study as low as possible. They believe that being in the study will not keep you from getting any treatments you may need for your disease.

This study will enroll people with your disease [CHOOSE WHICHEVER APPLIES]

• Whose disease has been treated unsuccessfully by all standard means
• Who will continue to receive standard treatment
• Who can probably put off standard treatment during the study
• Who can probably stop or change standard treatment during the study

Sample 3 - Phase I

This study is experimental. It is meant to investigate the safety, possible harms, and side effects of injecting your cancer with an experimental gene transfer agent called [X]. This is the first time that this gene transfer agent will be used in humans with your disease.

Sample 4 - Phase I

The investigator's goal is to find out the highest dose of the gene transfer agent that is safe. This is the first step in studying whether it can be used to treat others with your disease in the future.

Sample 5 - Phase II

The purpose of this study to find out if repeated doses of the gene transfer agent, [xx,] are safe for research participants with your disease, and to see if any side effects cause problems for participants. This study is also being done to find out if giving [xx] can help lung disease in CF by making normal genes in the lung cells.

Sample 6 - Phase III

The purpose of this study is:

• To find out if participants live any longer if the gene transfer agent is injected directly into their tumor(s)
• To find out if the intervention shrinks, stops or slows the growth of the tumor(s).

We will also continue to check the safety of the gene transfer agent.

PROBLEMATIC LANGUAGE

Problematic Samples

You have been invited to participate in this study because your disease has progressed despite standard treatment.

You are eligible to participate in this study because there is no effective treatment for your disease.

Comments: For early-phase studies, these statements, standing alone, may foster the perception that research participants are likely to benefit from study participation, simply because nothing else has worked for them. In order to avoid creating this impression, descriptions of the targeted study population should focus on how risks can be minimized in and knowledge can be gained from the population, as illustrated in Sample 2 above.

SAMPLE GENE TRANSFER DESCRIPTIONS

• The gene transfer used in this study tries to provide corrected copies of one of your genes that does not function properly in your body [can be used in studies supplying corrected genes for monogenic diseases, or the p53 gene for some cancers]
• The gene transfer method used in this study tries to add copies of a gene that will alter the characteristics of the targeted cells [for example, when inserting the HSV-TK gene into tumor cells to make them susceptible to destruction by gangiclovir]
• The gene transfer method used in this study tries to add copies of a gene that increases the immune response against a tumor [use, for example, when inserting the gene for IL-2 or interferon gamma]

SAMPLE VECTOR DESCRIPTIONS

• A virus called [adenovirus, adeno-associated virus, retrovirus, other virus, i.e. fowlpox, vaccinia], which has been changed in the laboratory so that it is not likely to reproduce or cause an infection once it is in your body. [A short description of each virus used in the vector should be added, as illustrated by the adenovirus description provided in the section above entitled "Describing Vectors."]
• Loops of DNA containing the gene [naked plasmids].
• Loops of DNA associated with fat molecules [called liposomes] that help improve gene delivery.
• If another delivery system is used to introduce the gene modified cells or to deliver the recombinant DNA directly (e.g., a gene gun) to a human, a brief description should be included in the consent form.