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Aggregated N-of-1 trials for unlicensed medicines for small populations: an assessment of a trial with ephedrine for myasthenia gravis

Overview of attention for article published in Orphanet Journal of Rare Diseases, May 2017
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Title
Aggregated N-of-1 trials for unlicensed medicines for small populations: an assessment of a trial with ephedrine for myasthenia gravis
Published in
Orphanet Journal of Rare Diseases, May 2017
DOI 10.1186/s13023-017-0636-y
Pubmed ID
Authors

Stephanie S. Weinreich, Charlotte Vrinten, Marja R. Kuijpers, Alexander F. Lipka, Kirsten J. M. Schimmel, Erik W. van Zwet, Christine Gispen-de Wied, Yechiel A. Hekster, Jan J. G. M. Verschuuren, Martina C. Cornel, Weinreich, SS, Vrinten, C, Kuijpers, MR, Lipka, AF, Schimmel, KJM, van Zwet, EW, Gispen-de Wied, C, Hekster, YA, Verschuuren, JJGM, Cornel, MC

Abstract

Inexpensive medicines with a long history of use may currently be prescribed off-label for rare indications. Reimbursement is at the discretion of health insurance companies, and may be unpredictable. The example addressed was ephedrine as add-on treatment for myasthenia gravis. Stakeholders from academia, a patient organization, the Dutch National Health Care Institute (NHCI) and Dutch Medicines Evaluation Board (MEB) advised on the trial design. The NHCI and MEB agreed to provide scientific advice on the suitability of the evidence generated by the trial, for regulatory decisions. This paper describes the feasibility of the trial and the utility of its aggregated results. The trialists experienced the trial as feasible. Retrospective interviews showed that the trial as performed was acceptable to patients. The treatment effect in the primary outcome measure, muscle strength, was statistically significant when inferred to the population level, though the effect size was modest. Secondary outcomes were statistically significant in a preplanned, fixed effects analysis within the four patients. The NHCI advised that it could potentially make reimbursement decisions based on the Fitting Evidence framework, should the trialists decide to apply for reimbursement. The MEB advised that for a licensing decision, the N-of-1 design is a last-resort option for demonstrating treatment benefit in a rare disease. N-of-1 trials alone do not provide enough evidence on potential risk. The MEB found the current trial inconclusive. It suggested doing a 2-armed trial of longer duration, possibly with a different outcome measure (postponement of corticosteroid use). It suggested engaging a consultancy or commercial sponsor, should the trialists decide to seek market authorization of the drug. In theory, evidence from aggregated N-of-1 trials is suitable for use in licensing and reimbursement decisions. The current example illustrates differences in interpretation of N-of-1 results by health authorities. In the era of personalized medicine, consensus is required on the interpretation of data from study designs geared to small groups. Demonstrating effectiveness of inexpensive medicines in small populations may require involvement of non-commercial parties, to preserve affordability.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 60 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 10 17%
Student > Ph. D. Student 9 15%
Researcher 8 13%
Professor 4 7%
Student > Doctoral Student 4 7%
Other 12 20%
Unknown 13 22%
Readers by discipline Count As %
Medicine and Dentistry 19 32%
Pharmacology, Toxicology and Pharmaceutical Science 5 8%
Economics, Econometrics and Finance 3 5%
Neuroscience 3 5%
Social Sciences 3 5%
Other 10 17%
Unknown 17 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 August 2017.
All research outputs
#9,319,541
of 11,655,615 outputs
Outputs from Orphanet Journal of Rare Diseases
#1,073
of 1,272 outputs
Outputs of similar age
#191,380
of 267,516 outputs
Outputs of similar age from Orphanet Journal of Rare Diseases
#26
of 31 outputs
Altmetric has tracked 11,655,615 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,272 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.8. This one is in the 8th percentile – i.e., 8% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,516 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 31 others from the same source and published within six weeks on either side of this one. This one is in the 6th percentile – i.e., 6% of its contemporaries scored the same or lower than it.