Clinical trials: how to think about one, and when to ask

What a clinical trial is. Why the time to ask about one is earlier than people expect. What taking part actually costs you in visits and travel. What the phases mean, and what to ask your own team.

The short version

A clinical trial is a study that tests a treatment nobody is certain about yet. A common belief is that a trial is what you try when everything else has failed. That is not how it works. There are five points in this illness where a trial might be open to you, and the first is before the operation that takes the tumor out. So the time to ask is now, whenever now is. Taking part costs you real things: more visits, more scans, often travel. And in many trials you do not get to choose which treatment you get. Nobody on this site can tell you whether a trial fits you. Your own team can, and that is the ask.

What is it, and what is it not?

It is a study you join, run to answer a question nobody can answer yet.

The question is usually one of two things: is this treatment safe enough to use, or is it better than what we already do. That is the whole of it. A trial is not a special hospital, and it is not a favor somebody does for you.

Two things follow.

• It is not a treatment somebody is sure about. If they were sure, it would not be a trial. That cuts both ways, and this page tries to say both.
• It is how the treatments you have already been offered got here. Many of the treatments used for brain tumors today were first studied in trials. Some of what you are on now was somebody's trial once.

And one thing it is not: it is not something this website can pick for you. There are companies that do that. Choosing a trial is a medical decision, and it belongs with the people who know your case. We list the trials we track and we explain how to think about them. Which trial, if any, is a conversation with your own team.

When should I ask?

Earlier than you think. If you read nothing else here, read this section.

The common belief is that a trial is a last resort, something for after the second or third time the tumor comes back. Brain tumor specialists say otherwise. There are five points in this illness where a trial may be open to a person, and three of them are before the tumor has come back at all:

1. Newly diagnosed, before surgery.
2. Newly diagnosed, before your standard treatment starts.
3. Newly diagnosed, after standard treatment and before the next stretch of it.
4. When it comes back, before surgery.
5. When it comes back, after surgery.

Read that list again if you were told a trial was for later. Three of those five doors are open early, and two of those three are about the time before treatment starts.

So ask at diagnosis if you can. The advice from brain tumor specialists is to raise it with your team as early as possible, ideally right at the start.

If you have already started treatment

You have probably not missed anything, and this is the part people get wrong.

Starting a treatment does not automatically rule you out of a trial. Some trials do ask that you have not had a particular drug, or that a certain amount of time has passed since you did. Others are written for exactly the person who has had standard treatment already. It depends entirely on the trial.

What is true is that it is worth planning ahead. Before you start anything new, it is a fair question to ask whether it would affect joining a trial later. That is not a reason to delay treatment. It is a reason to ask one extra question while the decision is being made.

One concrete example lives on another page: chemotherapy wafers put into the space at surgery can rule you out of some trials afterwards, because the drug they release makes the results hard to read. That is the kind of thing worth knowing before, not after.

What happens, step by step

1. You ask. "Is there a trial I should know about, here or anywhere else?" That one sentence is the whole beginning.
2. Your team looks at what fits. They know your diagnosis, your molecular results and what you have had already, which is what decides it.
3. You are told what the trial is testing and what the alternative is if you do not join. Ask for both.
4. You are screened. Tests to check you fit what the trial is looking for. Some people do not, and finding that out is not a rejection of you.
5. You go through consent. Somebody walks you through the whole thing before you decide anything. More on that below.
6. You decide. Either answer is a normal answer.
7. If you join, it starts, with a schedule of visits that is usually busier than ordinary care.

Getting from the first question to a yes or no can take weeks. That is worth knowing at the start, because the waiting is the part nobody warns people about.

What is being in one actually like?

Busier. This is the part the leaflets skip.

• More appointments, often at fixed times that are not negotiable, because the schedule is part of what is being studied.
• More scans and more blood tests than standard care, sometimes a lot more.
• Travel, if the trial runs at a center that is not your hospital. For some people that is the thing that decides it.
• Sometimes another biopsy, or a request for tissue already taken.
• Paperwork and diaries, and somebody phoning to ask how you are.

And it goes on for a while. Some trials run for months and some for years, and the follow-up can outlast the treatment. Ask how long yours runs and what happens at the end of it.

None of that is a reason not to do it. It is a reason to work out what it actually means for your week before you say yes, and to say the real answer out loud if it is too much. People do withdraw for this reason and it is allowed.

Will I get the new treatment?

In many trials, nobody chooses. Not you, and not your doctor.

Later-stage trials usually compare a new treatment against the treatment we already use. To make the comparison fair, people are put into groups by chance, most often by a computer. That is called randomizing.

This is worth being blunt about. If you join a randomized trial hoping to get the new thing, you may not get the new thing. You may get the standard treatment you would have had anyway. Joining is not a way of obtaining a particular drug.

Some trials are not like this, especially early ones where everybody gets the study treatment. Ask which kind you are being offered, because the answer changes what you are agreeing to.

Will I be given a sugar pill?

Rarely, and here is the shape of it.

A placebo, sometimes called a sugar pill, is a dummy treatment with nothing active in it. In cancer treatment trials they are rarely used. And if one is used, you are told before you decide. That is not a courtesy, it is how consent works.

When they are used, it is usually in one of two situations. One is where there is no standard treatment to compare against. The other is the reassuring one: everybody gets the standard treatment, and then one group gets the study drug on top and the other gets a placebo on top. In that design you are still getting the standard treatment.

So the question to ask is not "will there be a placebo". It is: if there is one, what do I get alongside it?

What do the phases mean?

Trials come in stages, and the stage tells you what question is being asked. It is worth a minute, because the stage tells you what the trial is for.

• Phase 1 asks whether the treatment is safe: what the side effects are, whether people can tolerate it, and how much can be given. Notice what is not on that list. A phase 1 trial is not designed to find out whether the treatment works. Some people do benefit, and that is not what is being measured.
• Phase 2 asks whether it seems to do anything to the tumor.
• Phase 3 compares it against the treatment we already use, to see whether it is actually better.
• Phase 4 happens after a treatment is approved and in ordinary use, and follows it over a longer time.

We do not print how many people are in each stage. The published figures disagree with each other, and a number would only be used to guess how risky a thing is, which is a question for the team running it.

Why this matters when somebody offers you a phase 1 trial. It is not a bad thing to be offered. But the honest version of what you are agreeing to is "help find out whether this is safe", not "receive a treatment that will help me". Both can turn out to be true. Only the first one is the plan.

Who is looking out for me?

More people than you would guess, and it is worth knowing they are there.

Consent is a conversation, not a form. Before you decide, the research team goes through the trial with you: what it is for, what will happen, and what could go wrong. You are allowed to take it home. You are allowed to bring somebody. You are allowed to ask every question twice.

You can leave at any time. Signing the form does not lock you in. Even after you have joined, even part way through, you can stop.

What we cannot tell you, and you should ask: what happens to your ordinary care if you leave. It is a reasonable thing to want in plain words before you sign, and the honest answer has to come from the team running the trial rather than from a website.

Somebody independent checks the trial before it opens, and keeps checking while it runs. A review board looks at the plan before anybody can join, looks again every year, and can change the trial or stop it altogether to protect the people in it.

And if something is found out while you are in it, you are told. New information about risks goes to the people taking part, not just into a report.

Will I hear what the trial found? That is a different question, and it is worth asking at the start rather than at the end. What you are promised is news about risks while you are taking part. Whether you get the trial's own result, and how long after, varies between trials. Ask who will tell you and when.

What will it cost me?

Some of it is usually covered, some of it may not be, and the only way to know is to ask which.

The trial's sponsor often pays for the research parts. Ordinary care costs may go to whoever normally pays for your care. And sometimes there are costs that land on you.

The ones people forget are not medical:

• Travel, and gas or fares.
• Somewhere to stay, if it is far.
• Parking, over and over.
• Meals.
• Care for children, or for somebody else you look after.
• Time away from work.

Some trials help with some of those. Ask the trial coordinator directly which costs are covered and which are not, and ask early, because for some people this is what decides it rather than anything medical.

How this works depends on where you live and how your care is paid for, so this page gives you the shape and not the rules. Your team, or the trial coordinator, can tell you how it works where you are.

What you need first

Most of this you probably already have. It is worth knowing what it is for.

This list is for the windows after your diagnosis is confirmed. If a trial is being discussed before the operation that takes the tumor out, some of it will not exist yet, and the trial team will say what they can work with.

• A confirmed diagnosis from tissue, with the molecular results. Trials are often written around a specific change in the tumor, so what the markers mean is the page for that half.
• A recent scan.
• Blood tests, to show the rest of you can cope with it.
• A record of what treatment you have had, and when. Dates matter here more than people expect.
• Some idea of how you are day to day. Teams measure this, and it is one of the most common things that decides whether a trial is open to somebody.

If a molecular result you might need has not been done, that is a fair thing to ask about in its own right.

For the person going with them

If you are the one driving to the appointments, keeping track of the pills, and lying awake at night worrying about them, this part is for you.

You are allowed to ask questions. In one study, families said they were afraid of annoying the doctor by asking too much. One of them was told by a doctor to stop playing doctor. Ask anyway. Write your questions down before you go, and bring a notepad. Two people in the room hear more than one.

Ask who your first call is. Care comes from a lot of people at once, and it is easy to end up as the only one holding it together. Ask the team: who do I call first? Some teams have one person whose job this is, often a nurse. Get the name and the number.

Get two numbers, and know which one to use. One for work hours, one for nights and weekends. Then ask what counts as "call us today" and what counts as "call an ambulance" for this tumor, and write the answer down where you can see it. If you are not sure which it is, call. Nobody on that team will mind.

If they have seizures, read about them before you need to. What to do when someone has a seizure is the one to know by heart. Living with seizures is about the rest of the time: what is safe, what to change, and driving.

Ask to be shown anything you are sent home to do. In that same study, families were sent home to change dressings and give medicines with no training at all. That is not fair to you. Before you leave the hospital, ask someone to show you. Then do it once while they watch.

Say what you notice. You may see a change before they do. Changes in thinking, mood and behavior can show up to the people close by first. Telling the team is not going behind their back. It is something the team cannot learn any other way.

Look after yourself, and let people help. Eat, sleep, and keep your own appointments. Take a little of the day back for yourself. When someone asks what they can do, give them a real job: a meal, a ride, an hour with the kids. Most people want to help and do not know how to offer.

You can talk to somebody about all of this today. See where to get help.

Three things that belong to a trial in particular.

You are probably the one absorbing the extra visits. The driving, the waiting room, the time booked off. It is fair to say out loud what is and is not possible before anybody commits, and it is better said at the start than in month three.

Go to the consent conversation. You already know two people hear more than one. This is the appointment where that matters most: the person being asked to decide is also the person with a brain tumor, and that is a lot to hold at once. Ask whether you can be there before the date is set.

Watch for the hope gap. It is very easy for one of you to hear "trial" as "chance" and the other to hear it as "experiment". Those are two different conversations happening in one kitchen. Saying which one you are having helps more than agreeing too quickly.

What to ask your team

• Is there a trial I should know about, here or anywhere else?
• What is being tested, and what is the alternative if I do not join?
• Would starting this treatment now affect a trial later?
• Is it randomized, and if it is, what are the groups?
• Is there a placebo, and if there is, what do I get alongside it?
• What phase is it, and what is that phase trying to find out?
• What extra visits, scans or procedures would I have?
• Which costs are covered, and which land on me?
• Can I leave, and what happens to my usual care if I do?
• Who do I call if something goes wrong at two in the morning?
• Do I need a molecular test I have not had yet?

Where to go next

• Find a clinical trial to see the trials we track, and to search the whole registry by ZIP code if you are in the US. It lists what is there; it does not tell you what fits.
• What the markers mean for the results a trial may be written around.
• Chemotherapy for the wafer question above.
• Brain tumor types if you want the page for your own tumor.
• Get help now if you need to talk to a person today.