PMID- 21932298
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20131121
IS  - 1539-1612 (Electronic)
IS  - 1539-1604 (Linking)
VI  - 10
IP  - 5
DP  - 2011 Sep-Oct
TI  - Determining the non-inferiority margin for patient reported outcomes.
PG  - 410-3
LID - 10.1002/pst.507 [doi]
AB  - One of the cornerstones of any non-inferiority trial is the choice of the 
      non-inferiority margin delta. This threshold of clinical relevance is very 
      difficult to determine, and in practice, delta is often "negotiated" between the 
      sponsor of the trial and the regulatory agencies. However, for patient reported, 
      or more precisely patient observed outcomes, the patients' minimal clinically 
      important difference (MCID) can be determined empirically by relating the 
      treatment effect, for example, a change on a 100-mm visual analogue scale, to the 
      patient's satisfaction with the change. This MCID can then be used to define 
      delta. We used an anchor-based approach with non-parametric discriminant analysis 
      and ROC analysis and a distribution-based approach with Norman's half standard 
      deviation rule to determine delta in three examples endometriosis-related pelvic 
      pain measured on a 100-mm visual analogue scale, facial acne measured by lesion 
      counts, and hot flush counts. For each of these examples, all three methods 
      yielded quite similar results. In two of the cases, the empirically derived MCIDs 
      were smaller or similar of deltas used before in non-inferiority trials, and in 
      the third case, the empirically derived MCID was used to derive a responder 
      definition that was accepted by the FDA. In conclusion, for patient-observed 
      endpoints, the delta can be derived empirically. In our view, this is a better 
      approach than that of asking the clinician for a "nice round number" for delta, 
      such as 10, 50%, pi, e, or i.
CI  - Copyright (c) 2011 John Wiley & Sons, Ltd.
FAU - Gerlinger, Christoph
AU  - Gerlinger C
AD  - Bayer Pharma AG-Global Clinical Statistics. christoph.gerlinger@bayer.com
FAU - Schmelter, Thomas
AU  - Schmelter T
LA  - eng
PT  - Journal Article
DEP - 20110919
PL  - England
TA  - Pharm Stat
JT  - Pharmaceutical statistics
JID - 101201192
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Acne Vulgaris/drug therapy
MH  - Acneiform Eruptions/drug therapy
MH  - Clinical Trials as Topic/*methods
MH  - Discriminant Analysis
MH  - Disease Progression
MH  - Drug and Narcotic Control
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Endometriosis/*complications/drug therapy
MH  - Female
MH  - Hot Flashes/complications/drug therapy
MH  - Humans
MH  - Internationality
MH  - Menopause/drug effects
MH  - Models, Statistical
MH  - Patient Satisfaction
MH  - Pelvic Pain/*complications
MH  - Pharmaceutical Preparations/metabolism
MH  - ROC Curve
MH  - *Research Design
MH  - Self Report/*standards
MH  - Sensitivity and Specificity
MH  - Treatment Outcome
MH  - United States
MH  - United States Food and Drug Administration
MH  - Vasomotor System/drug effects
EDAT- 2011/09/21 06:00
MHDA- 2012/06/26 06:00
CRDT- 2011/09/21 06:00
PHST- 2011/09/21 06:00 [entrez]
PHST- 2011/09/21 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
AID - 10.1002/pst.507 [doi]
PST - ppublish
SO  - Pharm Stat. 2011 Sep-Oct;10(5):410-3. doi: 10.1002/pst.507. Epub 2011 Sep 19.