PMID- 20032002
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20171116
IS  - 1740-7753 (Electronic)
IS  - 1740-7745 (Linking)
VI  - 7
IP  - 1
DP  - 2010 Feb
TI  - Use of a medication control officer to reduce bias in a clinical trial: lessons 
      learned from the scleroderma lung study.
PG  - 85-9
LID - 10.1177/1740774509355838 [doi]
AB  - BACKGROUND: Scleroderma Lung Study (SLS) was designed to evaluate the efficacy 
      and safety of oral cyclophosphamide (CYC) versus placebo taken for 1 year for 
      scleroderma-associated interstitial lung disease. An independent medication 
      control officer (MCO), usually a physician, at each center was assigned to 
      monitor laboratory and clinical toxicity of study medication and regulate its 
      dosing based on these results. By having an MCO who watched and managed toxicity, 
      the study investigators were free to care for study patients and to assess study 
      outcomes without the potential bias of knowing toxicity data (toxicity from 
      cyclophosphamide is distinctive - cytopenias and hematuria in particular). 
      PURPOSE: To assess the usefulness of an MCO, whose chief role was to maintain 
      safety while retaining the blinding in the clinical trial. METHODS: Patients had 
      safety laboratory testing every 2-4 weeks and results were sent directly to the 
      MCO within 2 days of the test. Other clinical adverse events (AEs) were reported 
      by the patient to a nurse coordinator who reported them to the MCO who then 
      managed the AEs to preserve the blinding of investigators caring for the 
      patients. The MCO was provided pre-determined algorithms for dose adjustments of 
      test medication based on the presence and severity of laboratory abnormalities. 
      RESULTS: Safety monitoring by the MCO was effective in the early detection of 
      drug toxicity with provision of appropriate medical intervention on a timely 
      basis. At the same time, investigator blinding appeared to be maintained. 
      LIMITATIONS: The testing of MCO effectiveness in maintaining blinding and 
      consistency was not defined as an a priori hypothesis and thus complete data 
      relating to the efficacy of the MCO were not collected in a prospective fashion. 
      CONCLUSION: An MCO and pre-specified monitoring and dosing guidelines, coupled 
      with uniform pre-specified responses to AEs, may be used effectively to preserve 
      investigator blinding and provide consistency in response to AEs in a clinical 
      trial setting, even when AEs of the test medication are distinctive.
FAU - Hsu, Vivien M
AU  - Hsu VM
AD  - Division of Rheumatology, UMDNJ Scleroderma Program, New Brunswick, NJ 08903, 
      USA. hsuvm@umdnj.edu
FAU - Khanna, Dinesh
AU  - Khanna D
FAU - Smith, Edwin
AU  - Smith E
FAU - Filemon, Tan
AU  - Filemon T
FAU - Whelton, Sean
AU  - Whelton S
FAU - Lopata, Mel
AU  - Lopata M
FAU - Davis, John C
AU  - Davis JC
FAU - Polito, Albert
AU  - Polito A
FAU - Heck, Louis
AU  - Heck L
FAU - Molitor, Jerry
AU  - Molitor J
FAU - Abeles, Micha
AU  - Abeles M
FAU - Granda, Jose
AU  - Granda J
FAU - Korn, Joseph
AU  - Korn J
FAU - Clements, Philip
AU  - Clements P
CN  - Scleroderma Lung Study Group
LA  - eng
GR  - K23 AR053858-03/AR/NIAMS NIH HHS/United States
GR  - UO1 HL 60606/HL/NHLBI NIH HHS/United States
GR  - UO1 HL60587/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091223
PL  - England
TA  - Clin Trials
JT  - Clinical trials (London, England)
JID - 101197451
RN  - 0 (Immunosuppressive Agents)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - *Bias
MH  - Clinical Protocols
MH  - Cyclophosphamide/administration & dosage/therapeutic use
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/therapeutic use
MH  - Lung Diseases/*drug therapy
MH  - Medication Therapy Management/*organization & administration
MH  - Multicenter Studies as Topic
MH  - Randomized Controlled Trials as Topic/standards
MH  - *Research Personnel
MH  - Scleroderma, Localized/*drug therapy
EDAT- 2009/12/25 06:00
MHDA- 2010/05/21 06:00
CRDT- 2009/12/25 06:00
PHST- 2009/12/25 06:00 [entrez]
PHST- 2009/12/25 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
AID - 1740774509355838 [pii]
AID - 10.1177/1740774509355838 [doi]
PST - ppublish
SO  - Clin Trials. 2010 Feb;7(1):85-9. doi: 10.1177/1740774509355838. Epub 2009 Dec 23.