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Research Methods · N-of-1 designs

Washout with a one-week half-life: the arithmetic

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SK
s.kimaniTL2 Moderator20 Nov 2024#1
Community wiki post. Any member at trust level 3 or above can edit this post; every edit is recorded. Last edited by PharmNotes_Whitfield on 27 Apr 2025. Editors: crossref_check, PharmNotes_Whitfield

Washout with a one-week half-life: the arithmetic — setting out what I have, and where I think it stops being reliable.

I have seen LEADER (N Engl J Med, 2016) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

51 likes 20mo
T
TavaresTL1Member21 Nov 2024#2

Objective versus subjective measures: subjective measures (how you feel) are vulnerable to bias. Objective measures (weight, strength on a specific exercise) are less vulnerable but not immune.

14 likes 20mo
PB
p.boatengTL2 Moderator21 Nov 2024#3
s.kimani, post #1: Washout with a one-week half-life: the arithmetic — setting out what I have, and where I think it stops being reliable. I have seen LEADER ( N Engl J Med , 2016) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows. My reading is that the trial is sound for its… Go to post

Blinding: blinding yourself (not knowing which condition you are in) removes expectation bias. This is hard to do with these compounds (the appetite suppression is hard to miss) but partial blinding is possible (measuring something objective without knowing whether you took it today).

5 likes in reply to #1 20mo
LC
l.chevalierTL3Regular22 Nov 2024#4
s.kimani, post #1: Washout with a one-week half-life: the arithmetic — setting out what I have, and where I think it stops being reliable. I have seen LEADER ( N Engl J Med , 2016) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows. My reading is that the trial is sound for its… Go to post

Washout periods: after stopping a medication, how long does it take for the effect to wash out? For compounds with a week-long half-life, roughly a month is needed to reach baseline. Using that washout period in a before-after design strengthens the inference.

0 likes in reply to #1 20mo
SF
s.ferreiraTL2 Moderator22 Nov 2024#5

I read post #3 twice before replying, because I had assumed the opposite.

Designing a personal experiment that could actually change your mind: that is the standard for an n-of-1 design. An experiment designed so that any result confirms what you already believed has not changed anything.

20 likes 20mo
CN
c.niemelTL3Regular22 Nov 2024 · edited#6

This follows post #3 rather than contradicting it.

Stopping rules: decide in advance when you will stop measuring (after a defined duration, after a defined number of measurements, or after a defined condition is met). Not deciding in advance means stopping when the result satisfies you, which is bias.

9 likes 20mo
RM
r.mwangiTL2 Moderator22 Nov 2024#7

When to run an n-of-1: this design works when you want to know whether a treatment works for you, not whether it works in general. For that purpose, it is efficient.

2 likes 20mo
B
BramleyTL2Member23 Nov 2024#8
s.kimani, post #1: Washout with a one-week half-life: the arithmetic — setting out what I have, and where I think it stops being reliable. I have seen LEADER ( N Engl J Med , 2016) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows. My reading is that the trial is sound for its… Go to post

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

0 likes in reply to #1 20mo
TI
t.ibarraTL2 Moderator23 Nov 2024#9

Statistical analysis of n-of-1 data: comparing before versus after with a t-test or similar is one approach. Plotting the data visually is another. Both are valid.

0 likes 20mo
TN
t.nardoneTL3Regular23 Nov 2024#10
l.chevalier, post #4: Washout periods: after stopping a medication, how long does it take for the effect to wash out? For compounds with a week-long half-life, roughly a month is needed to reach baseline. Using that washout period in a before-after design strengthens the inference. Go to post

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

27 likes in reply to #4 20mo
FV
f.villalobosTL2 Moderator24 Nov 2024#11

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

29 likes 20mo
VB
v.baptistaTL2 Moderator24 Nov 2024#12

Confounding in personal experiments: other things change when you start a medication (season, exercise, diet, stress). Documenting those confounders helps you understand their contribution to the result.

0 likes 20mo
BA
b.aaltoTL2 Moderator24 Nov 2024#13
l.chevalier, post #4: Washout periods: after stopping a medication, how long does it take for the effect to wash out? For compounds with a week-long half-life, roughly a month is needed to reach baseline. Using that washout period in a before-after design strengthens the inference. Go to post

Generalisability: a robust n-of-1 result applies to you. It does not tell you much about whether the effect generalises to others similar to you, much less to people different from you.

2 likes in reply to #4 20mo
TP
t.pereiraTL2 Moderator24 Nov 2024#14

On post #10 — agreed on the reasoning, with one qualification.

Blinding: blinding yourself (not knowing which condition you are in) removes expectation bias. This is hard to do with these compounds (the appetite suppression is hard to miss) but partial blinding is possible (measuring something objective without knowing whether you took it today).

9 likes 20mo
HF
h.ferrariTL225 Nov 2024#15
EL
e.lehtinenTL2 Moderator25 Nov 2024#16

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

0 likes 20mo
KC
k.chukwuTL2 Moderator25 Nov 2024#17
r.mwangi, post #7: When to run an n-of-1: this design works when you want to know whether a treatment works for you, not whether it works in general. For that purpose, it is efficient. Go to post

post #16 is right about the mechanism and I think understates the practical bit.

Generalisability: a robust n-of-1 result applies to you. It does not tell you much about whether the effect generalises to others similar to you, much less to people different from you.

1 like in reply to #7 20mo
RF
r.friskTL2 Moderator25 Nov 2024#18
f.villalobos, post #11: Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up. Go to post

Worth separating two things that post #14 runs together.

When to run an n-of-1: this design works when you want to know whether a treatment works for you, not whether it works in general. For that purpose, it is efficient.

6 likes in reply to #11 20mo
KK
k.kimaniTL2 Moderator25 Nov 2024#19

Picking up post #16: that is the part I would want checked first.

Stopping rules: decide in advance when you will stop measuring (after a defined duration, after a defined number of measurements, or after a defined condition is met). Not deciding in advance means stopping when the result satisfies you, which is bias.

15 likes 20mo
FF
f.fenwickTL3Regular26 Nov 2024#20

Coming back to post #18, because the follow-up matters more than the original answer.

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

30 likes 20mo
SO
s.oyelaranTL2 Moderator26 Nov 2024#21
r.frisk, post #18: Worth separating two things that post #14 runs together. When to run an n-of-1: this design works when you want to know whether a treatment works for you, not whether it works in general. For that purpose, it is efficient. Go to post

Coming back to post #19, because the follow-up matters more than the original answer.

Designing a personal experiment that could actually change your mind: that is the standard for an n-of-1 design. An experiment designed so that any result confirms what you already believed has not changed anything.

0 likes in reply to #18 20mo
M
MJayawardenaTL3Regular26 Nov 2024 · edited#22

Picking up post #19: that is the part I would want checked first.

Washout periods: after stopping a medication, how long does it take for the effect to wash out? For compounds with a week-long half-life, roughly a month is needed to reach baseline. Using that washout period in a before-after design strengthens the inference.

0 likes 20mo
RC
r.coelhoTL2 Moderator26 Nov 2024#23

Objective versus subjective measures: subjective measures (how you feel) are vulnerable to bias. Objective measures (weight, strength on a specific exercise) are less vulnerable but not immune.

13 likes 20mo
EM
endpoint_marginTL227 Nov 2024#24
TV
to.vargaTL2 Moderator27 Nov 2024#25

I read post #23 twice before replying, because I had assumed the opposite.

Confounding in personal experiments: other things change when you start a medication (season, exercise, diet, stress). Documenting those confounders helps you understand their contribution to the result.

1 like 20mo
CD
cohort_driftTL3Regular27 Nov 2024#26

Washout periods: after stopping a medication, how long does it take for the effect to wash out? For compounds with a week-long half-life, roughly a month is needed to reach baseline. Using that washout period in a before-after design strengthens the inference.

0 likes 20mo
IO
i.oseiTL2 Moderator27 Nov 2024#27
t.pereira, post #14: On post #10 — agreed on the reasoning, with one qualification. Blinding: blinding yourself (not knowing which condition you are in) removes expectation bias. This is hard to do with these compounds (the appetite suppression is hard to miss) but partial blinding is possible (measuring something objective without knowing whether you took… Go to post

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

18 likes in reply to #14 20mo
O
OTeixeiraTL3Regular27 Nov 2024#28

post #27 is right about the mechanism and I think understates the practical bit.

Objective versus subjective measures: subjective measures (how you feel) are vulnerable to bias. Objective measures (weight, strength on a specific exercise) are less vulnerable but not immune.

7 likes 20mo
MO
m.oyelaranTL2 Moderator28 Nov 2024 · edited#29

Confounding in personal experiments: other things change when you start a medication (season, exercise, diet, stress). Documenting those confounders helps you understand their contribution to the result.

4 likes 20mo
CI
citation_indexTL2Member28 Nov 2024#30

Statistical analysis of n-of-1 data: comparing before versus after with a t-test or similar is one approach. Plotting the data visually is another. Both are valid.

0 likes 20mo