I wanted to try a drug. I also wanted to be able to distinguish the direct effects of the drug from the placebo effects of the drug. Most importantly, I wanted to isolate placebo side effects. It seemed there was a chance of real side effects, and that meant that it was basically guaranteed that I would imagine those side effects. However, if I could tell that I was imagining them, I figured I might stop doing it.
The usual way to distinguish placebo effects from real effects is to have a bunch of people, and give half of them the real drug and half the placebo drug. Then if five percent of both groups gets a headache, you know that it’s entirely placebo headache.
Of course, that had already been worked out for this drug. It probably causes a few real side effects, and a few placebo ones. But what I wanted to know was whether the side effects were real in my own particular case.
If you want to figure this out, a natural idea is to get someone else to randomly give you drug or placebo on different days (or on different few-day bouts, if the drug takes time to act). After enough times, you can tell if the drug periods are better or worse.
This is a hard enough experiment to run on yourself if it takes a day for the drug to work. But what if the drug might take a month to work or to have side effects? Someone could randomize whether you get the drug or placebo for whole several month long stints, but at this point it will take you a year to get a few data points, and each one will be as different from the others as several month long periods are wont to be, aside from any effect from the drug. And you will have missed out on taking the drug for half a year.
Here is a different way to do this: randomize the start date. I asked a friend to pick a random day within the next few months, and then give me placebo pills until that day and from then on, a real pill. He did this by putting all the pills inside big red capsules so that I couldn’t tell them apart, and then put them in a pill advent-calendar, changing over at the right day. He wrote down the date of the switch. Then I took the pills, kept records of the thing I was trying to fix, and watched out for anything that seemed like the feared side effects.
This way, I was basically getting a bunch of somewhat different one-month periods in a row, without needing to allocate a month to each. If it took exactly one month for the drug to maybe start working, and I randomized the start date over three months, this would still be kind of like 90 one month trials, but overlapping, and in a very non-random order. Because day N and day N+1 are likely to have the same or very similar treatment, and are also similar for other reasons, this is hardly like 90 independent trials. But it seems a lot better than three (more) independent trials.
At the end of this, I could learn the true start date and compare it to time series of records. I did this by looking at the records first, and noting whether there was anything in them that looked like either something good happening, or a side-effect beginning. I figured that if I could correctly guess about when the real drug started, I would take that as decent evidence that it made some difference, good or bad.
One good byproduct of this arrangement is that it lowers the chance of actually imagining a side effect. Since on each day there was a very low chance that the drug had just started, I never had much reason to expect side effects if I didn’t already have them. I also didn’t think about it much. Consequently I never experienced the kind of side effects that I would have imagined. I did experience other things at around that time that might have been side effects, and didn’t notice any improvement, so ultimately gave up on the drug.
Alternatively, if you are more pessimistic and respond to a low chance of beginning to take a drug each day by imagining side-effects each day, you can easily tell that these are not real side effects because they will start before the drug. Or if instead you respond by imagining side-effects with low chance each day, they probably won’t line up with the real start date, so you can distinguish, unless the drug also causes side effects long after you started taking it, or with low probability each day. Still then, you can rule out all the things you imagine before the thing starts.
I’m not sure if this is a common method for avoiding placebo side-effects or for getting evidence about the positive effects of a drug, but I don’t remember hearing of other people doing it, so I thought I’d write about it.
Downsides include: you might not get to take the drug for months, and you might miss out on the positive placebo effects for the same reasons that you might miss out on the negative ones. And for some drugs, positive placebo effects are the main point of taking drugs.
Another downside is that you will have more interesting conversations with doctors. At one point I did this with a bunch of different drugs at once, many of which couldn’t be taken together, so I knew that I was maybe taking some unknown non-interacting subset, or nothing. This was complicated to explain to doctors when they asked me if I was taking any other medicines. ‘Um, with maybe 70% chance? No, I don’t know what they are, but I can give you a probability distribution. It’s fine, this boy I’m dating gives them to me and he says they are safe.’
I wanted to try a drug. I also wanted to be able to distinguish the direct effects of the drug from the placebo effects of the drug. Most importantly, I wanted to isolate placebo side effects. It seemed there was a chance of real side effects, and that meant that it was basically guaranteed that I would imagine those side effects. However, if I could tell that I was imagining them, I figured I might stop doing it.
The usual way to distinguish placebo effects from real effects is to have a bunch of people, and give half of them the real drug and half the placebo drug. Then if five percent of both groups gets a headache, you know that it’s entirely placebo headache.
Of course, that had already been worked out for this drug. It probably causes a few real side effects, and a few placebo ones. But what I wanted to know was whether the side effects were real in my own particular case.
If you want to figure this out, a natural idea is to get someone else to randomly give you drug or placebo on different days (or on different few-day bouts, if the drug takes time to act). After enough times, you can tell if the drug periods are better or worse.
This is a hard enough experiment to run on yourself if it takes a day for the drug to work. But what if the drug might take a month to work or to have side effects? Someone could randomize whether you get the drug or placebo for whole several month long stints, but at this point it will take you a year to get a few data points, and each one will be as different from the others as several month long periods are wont to be, aside from any effect from the drug. And you will have missed out on taking the drug for half a year.
Here is a different way to do this: randomize the start date. I asked a friend to pick a random day within the next few months, and then give me placebo pills until that day and from then on, a real pill. He did this by putting all the pills inside big red capsules so that I couldn’t tell them apart, and then put them in a pill advent-calendar, changing over at the right day. He wrote down the date of the switch. Then I took the pills, kept records of the thing I was trying to fix, and watched out for anything that seemed like the feared side effects.
This way, I was basically getting a bunch of somewhat different one-month periods in a row, without needing to allocate a month to each. If it took exactly one month for the drug to maybe start working, and I randomized the start date over three months, this would still be kind of like 90 one month trials, but overlapping, and in a very non-random order. Because day N and day N+1 are likely to have the same or very similar treatment, and are also similar for other reasons, this is hardly like 90 independent trials. But it seems a lot better than three (more) independent trials.
At the end of this, I could learn the true start date and compare it to time series of records. I did this by looking at the records first, and noting whether there was anything in them that looked like either something good happening, or a side-effect beginning. I figured that if I could correctly guess about when the real drug started, I would take that as decent evidence that it made some difference, good or bad.
One good byproduct of this arrangement is that it lowers the chance of actually imagining a side effect. Since on each day there was a very low chance that the drug had just started, I never had much reason to expect side effects if I didn’t already have them. I also didn’t think about it much. Consequently I never experienced the kind of side effects that I would have imagined. I did experience other things at around that time that might have been side effects, and didn’t notice any improvement, so ultimately gave up on the drug.
Alternatively, if you are more pessimistic and respond to a low chance of beginning to take a drug each day by imagining side-effects each day, you can easily tell that these are not real side effects because they will start before the drug. Or if instead you respond by imagining side-effects with low chance each day, they probably won’t line up with the real start date, so you can distinguish, unless the drug also causes side effects long after you started taking it, or with low probability each day. Still then, you can rule out all the things you imagine before the thing starts.
I’m not sure if this is a common method for avoiding placebo side-effects or for getting evidence about the positive effects of a drug, but I don’t remember hearing of other people doing it, so I thought I’d write about it.
Downsides include: you might not get to take the drug for months, and you might miss out on the positive placebo effects for the same reasons that you might miss out on the negative ones. And for some drugs, positive placebo effects are the main point of taking drugs.
Another downside is that you will have more interesting conversations with doctors. At one point I did this with a bunch of different drugs at once, many of which couldn’t be taken together, so I knew that I was maybe taking some unknown non-interacting subset, or nothing. This was complicated to explain to doctors when they asked me if I was taking any other medicines. ‘Um, with maybe 70% chance? No, I don’t know what they are, but I can give you a probability distribution. It’s fine, this boy I’m dating gives them to me and he says they are safe.’