Informed Consent for Clinical Trials

Introduction

Just as doctors obtain agreement from patients for surgery and other procedures, so too must researchers obtain agreement from volunteers to take part in clinical trials. The process of obtaining 'informed consent' is designed to protect individuals from being used unknowingly or against their will for medical studies. It is intended to inform potential volunteers of the risks, rights and benefits of taking part in a clinical trial, and in most cases, provide written documentation of their agreement to take part in the trial.

Written informed consent is not usually required in trials considered 'low risk'. These are trials where there is unlikely to be any invasive techniques, such as research studies involving focus groups or questionnaires.

The rest of this topic refers to trials where informed consent is required.

The Process

The participant information and consent form

One of the documents designed when a new clinical trial is being set up is the participant information and consent form (also called patient information sheets, or subject consent forms.) This document outlines for the potential volunteer why the trial is being done and by whom, the procedures and treatments involved, the responsibilities of the volunteer during the trial (for example: when they need to take medication, what activities or medications they should avoid, how often they need to visit the research centre, what tests and procedures will be done), the risks and benefits of the trial as compared to other treatments available, the framework in place to protect the patient's well-being, data and identity, any disclosures or conflicts of interest of the trial investigators, etc.

Within the international guidelines for clinical trials (ICH-GCP, section 4.8.10), there is a checklist of 20 points that must be covered in the participation information sheet with a view to fully informing volunteers. The way that this checklist is interpreted by different researchers can lead to quite different volumes of information being included, leading to information sheets that can vary from 2 to 20+ pages. Different countries may have implemented additional standards, guidelines or requirements on top of the basic guidance in ICH-GCP.

Ethical review of the informed consent process for a trial

The participant information and consent form will be one of the documents submitted for ethical review by the appropriate committee for trials in your country. Depending on the committee, information about the process of obtaining consent (for example who is responsible for consenting volunteers and their qualifications) may also be included in the submission.

The committee may request changes to the form if they believe the content is flawed, inappropriate, too much or too little, etc.

A trial will not be approved until the committee conducting the ethical review are satisfied that the trial is appropriate and that the information for potential volunteers is being provided in a way that will enable them to make an informed decision about whether or not to take part in the trial.

The Informed Consent Discussion

Once the trial is approved, the trial will be discussed with potential volunteers. This is when the participant information and consent form will be discussed and any questions answered.

Rather than informed consent, this discussion should rather be referred to as an informed decision making process. Just because the word consent is used, does not mean that a volunteer has to agree. The potential volunteer has the right to say no to a trial without it having any affect on their subsequent medical care or relationship with the researcher (or doctor).

Ethical guidelines such as the Declaration of Helsinki and Nuremberg Code require informed consent to be voluntary, not only technically but also spiritually. Volunteer should not feel pressured or coerced to say yes to a trial, and if they do, they should report it to the ethics committee that has reviewed the study (for which there should be contact details in the participant information and consent form).

Volunteers should feel free to ask as many questions as they like, and have those questions answered to their satisfaction, before and during a clinical trial. They should also feel free to seek external advice from their other doctors, family and friends if they need to in order to make a decision either way.

What can you expect in a consent form?

The informed consent has several parts that you should be sure you understand. If you don’t know the terms, ask for an explanation. Sentences are usually broken down into small sections, using commonly understood terms—such as “throw up” instead of vomit, “draw blood” instead of venipuncture, etc. If you still wonder about some of the words you find, ask about them.

Who? What? Why? When? Where? Are the basic questions you should ask, but in a consent form, they will be in a different order.

Who is doing the study?

Is the sponsor a drug company (pharmaceutical)? A University?

Who is responsible for taking care of me? How do I contact them?

Will I still see and be under the care of my primary (family) doctor?

What will they be doing to or for me?

What kinds of tests will be done? Will blood be drawn? If so, how much, and how often?

What else? What discomforts are involved? How does this compare to standard treatments?

Can I still take my other medications? Are there any known drug interactions?

What, if any, benefits are there for me?

Are there benefits for others? What (if any) medications will I receive? Side effects?

What are other risks? How serious are they likely to be? What are the chances that they will occur? :How are they different from risks associated with the standard care?

What, if any care is paid for by the sponsor?

What will I be responsible to pay? Who will pay for any complications, should they occur?

Will I receive any money for my time, transportation, child care, or other expenses?

What happens when the study ends?

Will I still be able to receive the study medicines, if they were helping me? Who will pay for this?

Why is this study being done?

Is it to learn more about the basic disease or problem?

Is it to develop a new treatment where none currently exists?

Is it mostly for marketing, to say, “My drug is better than your drug?”

Why does the investigator believe the new medicine, device, or treatment may be effective?

How is it different from the standard treatment?

When will each study activity occur?

How long will I be on this protocol? How many visits are required? How long will each visit take?  :Are there other inconveniences?

Where will the study be done?

Will I be in a hospital? Do I have to stay overnight or is this just an outpatient visit?

You should be asked to review and agree to the informed consent before any study procedures are performed. Once you make a commitment, investigators hope that you will complete the trial. But sometimes things happen—and one important fact to remember is that you can change your mind and withdraw your consent for participation at any time.

It can be frustrating for an investigator when a patient declines to participate in a trial because of fear, but then asks nothing and prefers to know nothing about his or her approved regular medicines that, in fact, may be more toxic than the investigational medicine. You should ask questions about all of your medicines and procedures, and be an active participant in your care.

“Do I want to do this?” is the final question you should ask yourself? Does this sound like a worthwhile project that I want to help with, or would I be better off waiting and looking for something else? This is a very personal decision, and your participation should be voluntary.

If agreeing to take part in a trial

At the end of the informed consent process, if the volunteer agrees to go in the trial, the volunteer and the researcher that was involved in the informed consent discussion will usually sign and the consent form to document that the volunteer agrees to take part. The volunteer should be given a copy of the participant information and consent form for their future reference.

Once in the trial

Once in the trial, a volunteer also has the right to withdraw from a study at any time, for any reason. Volunteers should only consent to trials they have the intention of completing. However, there are times when once in the trial, a volunteer may not be able or want to continue. For example, they felt they were misled about the number of visits or procedures, they move house and can't get to visits easily, they don't feel well on the trial and want to get off it, or any other reason at all.

If a volunteer wants to withdraw, they should tell the research team so that they can make sure the volunteer stops the study treatment safely, and are appropriately followed up medically. The volunteer will usually also be asked whether they consent to the information that has been collected so far in the trial is still OK to be used, or whether they can be contacted at a later date for any follow-up information. Once again, this decision should be made voluntarily by the trial participant.

The Ethical Challenges of Informed Consent

It would appear on the surface that if someone indicates agreement with participation in a trial, that informed consent has been taken.

However, researchers often have difficult ethical challenges to consider when they are obtaining informed consent for trials.

Here are a few examples where there are outside considerations that could impact whether informed consent has truly been obtained.

1. Imagine a trial where person is admitted to the emergency room having just had a stroke. This person may or may not be fully competent to make a decision about their treatment. In some cases, the doctor may need to treat the patient with a drug within an hour of the stroke, so decisions need to be made very quickly. If one of the treatment options is a clinical trial, can a doctor fully explain all the treatment options (including the trial) and give the patient (or their family) enough time to consider which treatment option they want?

2. Imagine a trial is conducted in a country where there is not significant medical care freely available for the condition being treated. This doesn't just happen in developing countries where this is an obvious dilemma, but is also possible in western countries such as the USA, where treatment may only be available depending on your level of healthcare coverage. Is a potential volunteer really going to be able to choose not to take part in a trial if there is no other treatment freely available to them? Would it be more ethical for the doctor not to offer the trial (because the volunteer will be unduly influenced to take part based on their own circumstances), or to offer the trial (giving equity in access to treatment to all).

3. Imagine there is a new treatment being tested for patients with Alzheimer's Disease. Depending on the stage of their disease, or whether it is a good or bad day, the patient may not be able to fully comprehend the trial or the risks involved. In these cases, a legal guardian for the patient must agree for the patient to take part in the trial. But how does a doctor know whether a patient is able to consent for themself, or whether a legal guardian should be involved?

4. When a treatment is first trialled in humans, in most cases it is done in healthy people. Because there are no potential benefits to the healthy people for taking part, it is considered only appropriate to compensate these volunteers with money that covers the time they were involved in the study. However, the most healthy in our population able to make decisions for themselves (the 18-30+ year olds) are often also less financially secure. For example they might be university students, backpacking travellers, or young unemployed people, and with a 'nothing can hurt me' attitude, be more than willing to take part in these trials for the financial rewards they provide. Will these volunteers provide informed consent in a way that hasn't been unduly influenced by the offer of compensation?

5. It is important to provide potential volunteers with everything they need to know about the trials before deciding whether they would like to take part. Due to increasing regulatory and legal requirements, the length of these information sheets is getting longer and longer. If a participant information and consent form is 10 or more pages long, will a potential volunteer really remember and understand everything in this document before deciding whether to take part? Is informed consent really obtained with these long forms? How much should doctors 'test' and document the understanding of the patients before assuming informed consent is given?

6. Imagine a cancer patient that has run out of all available options and is offered a trial. Given the patient may be full of hope for any treatment offered at that stage, will their consent to take part in a trial be informed and uninfluenced?

7. At what age is a child able to consent for themselves to their participation in a trial? If the child is young, what does a researcher do if one parent agrees to their child taking part, but the other parent does not?

These are just a few of the ethical dilemma's facing researchers seeking informed consent from volunteers. Regulations and guidelines are generally in place to guide researchers in the completing this process in an ethical way. However, as can been seen above, informed consent can be a controversial issue.

More information

For more information about clinical trials, please visit these other Medpedia pages:

Clinical Trials
Types of Clinical Trials