Reducing the probability of false positive research findings by pre-publication validation - experience with a large multiple sclerosis database.
BACKGROUND
Published false positive research findings are a major problem in the process of scientific discovery. There is a high rate of lack of replication of results in clinical research in general, multiple sclerosis research being no exception. Our aim was to develop and implement a policy that reduces the probability of publishing false positive research findings. We have assessed the utility to work with a pre-publication validation policy after several years of research in the context of a large multiple sclerosis database.


METHODS
The large database of the Sylvia Lawry Centre for Multiple Sclerosis Research was split in two parts: one for hypothesis generation and a validation part for confirmation of selected results. We present case studies from 5 finalized projects that have used the validation policy and results from a simulation study.


RESULTS
In one project, the "relapse and disability" project as described in section II (example 3), findings could not be confirmed in the validation part of the database. The simulation study showed that the percentage of false positive findings can exceed 20% depending on variable selection.


CONCLUSIONS
We conclude that the validation policy has prevented the publication of at least one research finding that could not be validated in an independent data set (and probably would have been a "true" false-positive finding) over the past three years, and has led to improved data analysis, statistical programming, and selection of hypotheses. The advantages outweigh the lost statistical power inherent in the process.
Daumer
Martin
M
Sylvia Lawry Centre for MS Research, Hohenlindener Str, 1, 81677 Munich, Germany. daumer@slcmsr.org
Held
Ulrike
U
Ickstadt
Katja
K
Heinz
Moritz
M
Schach
Siegfried
S
Ebers
George
G
D016208:Databases, Factual; D004185:Disability Evaluation; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis; D011643:Publishing / Q000592:standards; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D015203:Reproducibility of Results