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A pair, drawn from abstracts · the eight full-text graphs

OnabotulinumtoxinA for chronic migraine: the PREEMPT pair

Question: does onabotulinumtoxinA prevent chronic migraine? PREEMPT 1 missed its pre-specified primary endpoint, headache episodes, and met its secondary endpoints, headache days and migraine days. PREEMPT 2, published in the same issue, had headache days as its primary endpoint and met it. One graph across two papers shows a hypothesis, an opposing result, a revised measure and a supporting result. It is a negative result SAGE itself published.

Health Sciences · a pair · bronze open access, not CC BY. Drawn from the abstracts, because these full texts are not open. No experiment is proposed on this page: a design needs the methods section, and a graph of a paper that is not CC BY cannot carry one here. The eight · All graphs

How to read these graphs

A discourse graph breaks a piece of research into typed one-sentence nodes and draws how they bear on one another. The grammar is that of Discourse Graphs (Chan and Akamatsu). Read each graph left to right: a question, the experiments that addressed it, the results they produced, and the hypothesis every result is drawn against.

QUE Question
What the work set out to answer.
HYP Hypothesis
The answer the authors expected. Every result earns one edge against it.
EXP Experiment
One attempt at the question: a trial arm, an assay, a survey, an analysis.
RES Result
One finding from an experiment, with where in the source it comes from.
ISS Issue
An open question or untried branch the work leaves for someone else.
addresses
An experiment addresses the question.
produces
An experiment produces a result.
supports
A positive result that backs the hypothesis.
opposes
A negative result that counts as evidence against the hypothesis, or a refutation of an earlier claim.
informs
A partial or mixed result that bears on the hypothesis without settling it.
consistent with
A negative or inconclusive result that does not count either way: no positive control passed, or there is no sensitivity or power statement, so the absence of an effect cannot be told from a measurement that failed.
relation
A thin dotted line: a link the source itself states between two experiments, such as one being derived from another.

A dashed box marks a result the rule above counts as uninformative, or an issue. In the drawing, click a node to jump to its text below.

OnabotulinumtoxinA for chronic migraine: the PREEMPT pair (Cephalalgia, 2010)

Health Sciences · a pair · bronze open access, not CC BY

Read left to right. The question (QUE) is addressed by 2 experiments (EXP), each producing results (RES), and each result bears on the hypothesis (HYP). 4 support it, 1 oppose it, 2 inform it. Issues (ISS) hang below: what the paper leaves open.

Discourse graph of OnabotulinumtoxinA for chronic migraine: the PREEMPT pair (Cephalalgia, 2010) que addresses preempt-1 que addresses preempt-2 preempt-1 produces p1-episodes p1-episodes opposes hyp preempt-1 produces p1-days p1-days supports hyp preempt-1 produces p1-migraine p1-migraine supports hyp preempt-1 produces p1-safety p1-safety informs hyp preempt-2 produces p2-days p2-days supports hyp preempt-2 produces p2-secondary p2-secondary supports hyp preempt-2 produces p2-safety p2-safety informs hyp preempt-2 comparedWith preempt-1: the second of a pair of studies; same design, different primary endpoint ISS · open questions and untried branches this path leaves behind QUE · partial Does onabotulinumtoxinA, injected every 12 weeks, prevent headache in adults with chronic migraine? Does onabotulinumtoxinA, injected every 12 weeks, prevent headache in adults with chronic migraine? HYP Compared with placebo, 155–195 U of onabotulinumtoxinA every 12 weeks reduces headache frequency at week 24. Compared with placebo, 155–195 U of onabotulinumtoxinA every 12 weeks reduces headache frequency at week 24. EXP · partial PREEMPT 1: 24-week double-blind placebo- controlled phase, 341 active vs 338 placebo; primary endpoint headache episodes PREEMPT 1: 24-week double-blind placebo-controlled phase, 341 active vs 338 placebo; primary endpoint headache episodes RES · negative-no-effect Headache episodes (primary): −5.2 vs −5.3, p = 0.344. No between-group difference. Headache episodes (primary): −5.2 vs −5.3, p = 0.344. No between-group difference. RES · positive Headache days (secondary): significant between-group difference, p = 0.006. Headache days (secondary): significant between-group difference, p = 0.006. RES · positive Migraine days (secondary): significant between-group difference, p = 0.002. Migraine days (secondary): significant between-group difference, p = 0.002. RES · positive Safe and well tolerated; few treatment- related adverse events, few discontinuations. Safe and well tolerated; few treatment-related adverse events, few discontinuations. EXP · positive PREEMPT 2: 24-week double-blind placebo- controlled phase, 347 active vs 358 placebo; primary endpoint headache days per 28 days PREEMPT 2: 24-week double-blind placebo-controlled phase, 347 active vs 358 placebo; primary endpoint headache days per 28 days RES · positive Headache days per 28 days (primary): −9.0 vs −6.7, p < 0.001. Headache days per 28 days (primary): −9.0 vs −6.7, p < 0.001. RES · positive All secondary endpoint comparisons favoured onabotulinumtoxinA. All secondary endpoint comparisons favoured onabotulinumtoxinA. RES · positive Discontinuation for adverse events 3.5 % active vs 1.4 % placebo; safe and well tolerated. Discontinuation for adverse events 3.5 % active vs 1.4 % placebo; safe and well tolerated. ISS · open-question The primary endpoint differs between the two trials (episodes, then days). Neither abstract says why, or when the change was made. The primary endpoint differs between the two trials (episodes, then days). Neither abstract says why, or when the change was made. ISS · open-question Large within-group decreases were seen in both arms of PREEMPT 1. How much of the effect on days is placebo response? Large within-group decreases were seen in both arms of PREEMPT 1. How much of the effect on days is placebo response? ISS · untried Is headache-episode frequency a less sensitive measure than headache days, or a different construct? Is headache-episode frequency a less sensitive measure than headache days, or a different construct?
  • supports positive finding
  • opposes a negative with a control and a stated sensitivity, or a failed replication
  • informs bears on the question without deciding the hypothesis
  • thin grey a relation between two experiments
Nodes, in reading order. Sources: Aurora et al. 2010, 10.1177/0333102410364676; Diener et al. 2010, 10.1177/0333102410364677; abstracts.
NodeTextTypeOutcomeEdge
EXPPREEMPT 1: 24-week double-blind placebo-controlled phase, 341 active vs 338 placebo; primary endpoint headache episodes
Primary endpoint not met; secondary endpoints met.		randomized trialpartial
RESHeadache episodes (primary): −5.2 vs −5.3, p = 0.344. No between-group difference.
headache episodes, change from baseline		negative-no-effect
informative		opposes HYP
RESHeadache days (secondary): significant between-group difference, p = 0.006.
headache days		positive
informative		supports HYP
RESMigraine days (secondary): significant between-group difference, p = 0.002.
migraine days		positive
informative		supports HYP
RESSafe and well tolerated; few treatment-related adverse events, few discontinuations.
adverse events		positive
informative		informs HYP
EXPPREEMPT 2: 24-week double-blind placebo-controlled phase, 347 active vs 358 placebo; primary endpoint headache days per 28 days
Primary and all secondary endpoints met.		randomized trialpositive
RESHeadache days per 28 days (primary): −9.0 vs −6.7, p < 0.001.
headache days per 28 days		positive
informative		supports HYP
RESAll secondary endpoint comparisons favoured onabotulinumtoxinA.
secondary endpoints		positive
informative		supports HYP
RESDiscontinuation for adverse events 3.5 % active vs 1.4 % placebo; safe and well tolerated.
discontinuations		positive
informative		informs HYP
  • ISS The primary endpoint differs between the two trials (episodes, then days). Neither abstract says why, or when the change was made. (open-question)
  • ISS Large within-group decreases were seen in both arms of PREEMPT 1. How much of the effect on days is placebo response? (open-question)
  • ISS Is headache-episode frequency a less sensitive measure than headache days, or a different construct? (untried)

Licence

These two graphs are drawn from the abstracts of papers that are not open access. The abstracts are freely readable on journals.sagepub.com, nothing beyond them was used, and the graphs quote them only in short. They are kept because each shows a claim and the later SAGE paper that tested it, in one picture.