Study Groups
When people agree to participate in a clinical trial, they are put in one part of the study or another; these different parts are called study “arms” or groups.
People are assigned to their group and do not get to choose. Different study groups may receive different treatments or participate in different activities. Sometimes there will be a study group that does not receive the treatment or activity being tested, but instead receives an inactive substance called a “placebo” or an alternative intervention. As Bianca puts it, in her trial she knew she “would either be on a placebo or on the actual drug.” Sally was worried about her study group assignment at first but decided to stick with the trial anyway.
Dr. Ellen Mowry talks about study groups and placebos.
Dr. Ellen Mowry talks about study groups and placebos.
Study groups, in the context of trials, really refer to different groups within the population you’re evaluating receiving different interventions, essentially. And so, you know what those interventions are and how they differ depend on the trial. Sometimes you’re comparing one active intervention, say medication ‘A,’ to the standard of care that already exists, medication ‘B.’ Or you’re comparing two, you know, novel medications, ‘C,’ ‘D’ versus each other or combinations, add-ons, things like that. Sometimes, instead of comparing medication ‘A’ to medication ‘B,’ you’re comparing medication ‘A’ to nothing; to a pill that isn’t expected to have any impact, and that’s what a placebo is.
In those cases, say we’ll do medications ‘Z’ versus medication ‘Y.’ Like, is ‘Z’ better than the standard of care? Or, if it seems safe, what if we just gave everybody medication ‘Y’ and then added ‘Z’ to half of the people. One study group will get extra treatment, you know.
Blinding refers to not allowing some people involved in this study, whether it’s the participants or the people assessing the outcomes of the intervention, or both, from knowing what intervention a given participant got. And blinding is helpful because we all carry forward our biases about an intervention and whether we think it is likely to have an impact on the outcome ….
In clinical trials, we want to minimize that kind of bias ….
It’s important not to attribute the benefit of an intervention to the intervention when in fact, it’s something else. So, binding is really good for that.
Knowing and Finding Out Your Study Group
Most people were not told what study group they had been assigned but a few were informed. Bianca says she wasn’t “supposed to know if [she] was on a placebo or the drug.” Fred was in a study with four groups and end up in the “one with the shot.” Debra C. felt great when she was assigned the diet protocol she wanted. Nijay and Amy’s child was assigned to a group where she got “the most of everything, the most chemo, the most spinal taps.” They say they might not have enrolled their daughter if they had known she would be in this group because all that treatment can create risk for cognitive side effects later in life.
Some people had guesses about which group they may have been in. Elaine’s trial team suspected she had the placebo based on what her blood tests showed. Susan didn’t know what group she was in during her trial but wondered if she might have been in a group that got a higher dose because of her side effects. Debbie and Mercedes similarly knew what group they were in based on physical reactions they had.
In Susan’s trial, study group assignments changed in different phases of the trial.
In Susan’s trial, study group assignments changed in different phases of the trial.
But you– you go in and you don't know then because I had to take these pills. I think it was four times, three or four times a day. I don't remember. And you get these pills, and they give them to you for the month. And you don't know if they're placebos or the real thing, because that's the study, is your—you know, what group you're in, so they don't know, you don't know.
And then at the end of that time, when we went to the next phase– was the next phase– phase three, I believe, as when they gave everybody– everybody got the medication. But some got at different doses so you didn't know what dose you got, but you got– you got the real drug. Well, I knew I had the placebo the first time I took the first dose of the drug. I knew I had the placebo because I thought, nah, this is something not right about this drug. And then it didn't take me but– I don't know, I think I was only on it 2 weeks, 2 and 1/2 weeks, because I had every side effect. I had itching, and I could hardly eat anything, and I had the diarrhea, and I'm like this is not– so then I had to finally call the neurologist and say, I think I have the real medication, and I think I have every side effect you want to think about. And then I had to stop, and I had to dis-enroll because it was too unsafe. I couldn't– I couldn’t eat. I couldn't keep anything down. So you know, I don't know what dose I was on. Could I have taken the smaller dose and been more comfortable? Maybe so. Who knows?
Jennifer A. thinks she knows what group she was in.
Jennifer A. thinks she knows what group she was in.
And then they put us into one of three groups. One was a constant, so nothing changed. One person had some behavior cognitive therapy, normal. And then one had some cognitive behavioral therapy tailored for MS. So, you're always secretly hoping you get the MS-specific one, but the worst thing you're doing is getting paid to live your life the same. So, I'm pretty sure I got in the MS-specific one, but I'll never know. But I had a social worker call me once a week and just go through a cognitive behavior program talking about the uncertainties, what parts of the uncertainty of MS were hard for me, and then some coping mechanisms.
Some people never found out what study group they were in. David R. asked at the end of the trial “whether I was in the placebo or the real thing,” but the trial team couldn’t tell him. When Julia asked which group she had been in, she never heard back. Mia said, “I mean, it was a double-blind study. I know what that means. Some get placebo, some don't. But at the end of the study, I didn't know it at the time—nobody ever said that you were not going to—it never even came up.”
Mia was frustrated that she never found out what group she was assigned.
Mia was frustrated that she never found out what group she was assigned.
Well, at the end of it-- it lasted for nine months. And at the end of it, I never even found out what was working for me. Because they never even told me what I was taking. And I made kind of a big deal about it to [INSTITUTION] and to the big pharma company that was sponsoring it that I wanted it in my medical chart, what I took. Because that's very important for my doctors to know. And no, they didn't get that either. And I still don't know what I took or anything.
But unless I'm sitting right there-- that study was-- because I just never knew. And I thought that was really frustrating, still not knowing. Was it the placebo? Because it didn't always make-- when you go on and off medications like that, they would always give you-- there would be a two-week period in between. You did the red and the blue bottle for two weeks and then for two weeks you wouldn't do anything, so you could get it all out of your system before you start another one.
People who did find out what study group they are in, found out at different times. Debra C. knew from the beginning of her trial: “you were assigned a group to be in and which meal plan you were going to have to do for the duration.” Joan and Debbie found out at the end of their trials. Alejandro will find out whether he took the placebo medication or the “real deal” after the study results are published.
Being in the Placebo Group
People had different experiences being in the placebo group, the control group, or the “usual group” that didn’t receive any active treatment. Elaine hoped not to be in the placebo group: “I get the placebo, well, nothing has changed. If I don’t get the placebo, well, then things might change. You know, I was excited.” Nora similarly wished that she had been in the other study group for her trial, since her fatigue wasn’t helped by the hypnosis intervention that her group got, and she couldn’t even receive information about strategies to help with fatigue until the trial ended. When Tiffany was randomized into the placebo group, she thought “it kind of sucks that I don't get treatment but it's nice that I got to live my normal daily life.” For Jennifer A., being in the placebo group meant “the worst thing you're doing is getting paid to live your life the same.”
Jason talks about his experience being in the placebo group.
Jason talks about his experience being in the placebo group.
And then I've done a couple-- I've done a couple of research studies. One of them was-- I got put into a control group for one. So, I didn't actually do anything. I just took surveys. I took a survey at the beginning. And then I was in the control group that had no thing-- nothing added, just live life normal. And then I took the same survey at the end. That was cool. I didn't do anything, didn't get anything out of it.
Kara did not sign up for trials where she could be in the placebo group.
Kara did not sign up for trials where she could be in the placebo group.
What did you think about sort of the chance of being in the placebo group or getting the medication?
The-, the clin-, the trials I was at, I was not going to be in a placebo trial, or the placebo group. Like, the placebo group was not an option. So, I don’t remember why with the first one, because it’s been so long, but I was guaranteed, I was 100% guaranteed to get the medicine for-, and, and for the Tysabri as well, like it was a 100% guarantee. And that was another reason why we chose that first medicine was that I needed medicine.
Oh.
And I didn’t-, my neurologist did not-, was not going to put me on any medicine that I could potentially be in a placebo trial. So, that’s why we chose that one. So, I’ve never had a risk for that.
Bianca talks about the placebo group being part of scientific discovery that helps everyone.
Bianca talks about the placebo group being part of scientific discovery that helps everyone.
What did you think about the idea of being randomized to either the placebo or the study drug?
Well, it was sort of all in the name of science. I don't think I had any great, great hopes. And I don't think I was thinking, oh, I'm going to be really disappointed if I just get the placebo. Because I thought, eventually, OK, well, if this drug turns out to help people with MS and is safe, then Dr. [NAME] will put me on this drug when the trial is done. So, for me, it was, OK, so maybe there's a delay of several months. If I'm just getting a sugar pill or whatever, eventually, if it's considered worthwhile, I was totally confident that he would put me on it if he thought it could do something. So even if it were a regular prescribed drug, I would have given it a try. But I was getting weary of the injection medications. And yeah, but I would've done anything. I just kind of gave up on medications helping my particular case.