PMID- 19029209
OWN - NLM
STAT- MEDLINE
DCOM- 20090303
LR  - 20211020
IS  - 1740-7745 (Print)
IS  - 1740-7753 (Electronic)
IS  - 1740-7745 (Linking)
VI  - 5
IP  - 6
DP  - 2008
TI  - Use of biological assignment in hematopoietic stem cell transplantation clinical 
      trials.
PG  - 607-16
LID - 10.1177/1740774508098326 [doi]
AB  - BACKGROUND: When comparing treatments for a specific illness, it is sometimes 
      impractical or impossible to conduct a randomized clinical trial (RCT). 
      Biological assignment trials are one alternative design. In hematopoietic stem 
      cell transplantation (HCT) trials, a human leukocyte antigen (HLA)-matched 
      sibling donor is considered optimal, but such donors are available for only 
      20-30% of otherwise eligible patients. Rather than randomizing only those with a 
      matched sibling donor, in a recent multiple myeloma trial, the type of HCT each 
      patient received was biologically based, i.e., chosen according to whether or not 
      the patient had a matched sibling donor. PURPOSE: This article describes the 
      design and implementation of biological assignment trials as well as their 
      advantages and disadvantages. METHODS: We focus on several aspects of such 
      trials, including efficiency of trial duration, ethical issues, and potential 
      sources of bias. Statistical issues are considered including sample size 
      calculations, monitoring for biased enrollment, and adjustments for imbalances in 
      patient characteristics. A multiple myeloma trial is used as an illustration. 
      RESULTS: Although they often require a larger sample size, biological assignment 
      trials can provide substantial efficiency in terms of study duration over 
      randomized trials when accrual to a randomized trial would be slow. Determination 
      of sample size requires consideration of the anticipated proportion of patients 
      with a biologically favored (HLA-matched sibling) donor. An add-on randomization 
      of patients without a matched sibling donor may alleviate ethical concerns about 
      applicability of study results to all patients regardless of whether the 
      biological assignment groups differ with respect to outcome. LIMITATIONS: 
      Prognostic factor imbalance and enrollment bias can occur in a biological 
      assignment trial. Statistical adjustment for potential imbalance in prognostic 
      factors is important, as is monitoring center accrual for enrollment bias and 
      performing an appropriate intention-to-treat analysis. CONCLUSIONS: A biological 
      assignment trial can be a reasonable way to compare treatments which are 
      biologically based, such as HLA-matched sibling transplants, when the 
      gold-standard randomized trial design is impractical or impossible. Implementing 
      such a trial requires careful consideration of the ethical issues and potential 
      biases.
FAU - Logan, Brent
AU  - Logan B
AD  - Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA. 
      blogan@mcw.edu
FAU - Leifer, Eric
AU  - Leifer E
FAU - Bredeson, Chris
AU  - Bredeson C
FAU - Horowitz, Mary
AU  - Horowitz M
FAU - Ewell, Marian
AU  - Ewell M
FAU - Carter, Shelly
AU  - Carter S
FAU - Geller, Nancy
AU  - Geller N
LA  - eng
GR  - U10 HL069294/HL/NHLBI NIH HHS/United States
GR  - U24 CA076518/CA/NCI NIH HHS/United States
GR  - U10 HL069330/HL/NHLBI NIH HHS/United States
GR  - U01-HL-69294/HL/NHLBI NIH HHS/United States
GR  - U01 HL069294/HL/NHLBI NIH HHS/United States
GR  - U01 HL069294-07/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Clin Trials
JT  - Clinical trials (London, England)
JID - 101197451
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Feasibility Studies
MH  - *HLA Antigens
MH  - Hematopoietic Stem Cell Transplantation/methods
MH  - *Histocompatibility Testing
MH  - Humans
MH  - Multiple Myeloma/immunology/therapy
MH  - *Patient Selection
MH  - *Random Allocation
MH  - *Randomized Controlled Trials as Topic
MH  - Selection Bias
MH  - Transplantation, Autologous
MH  - Transplantation, Homologous
PMC - PMC2671015
MID - NIHMS102157
EDAT- 2008/11/26 09:00
MHDA- 2009/03/04 09:00
PMCR- 2009/04/21
CRDT- 2008/11/26 09:00
PHST- 2008/11/26 09:00 [pubmed]
PHST- 2009/03/04 09:00 [medline]
PHST- 2008/11/26 09:00 [entrez]
PHST- 2009/04/21 00:00 [pmc-release]
AID - 5/6/607 [pii]
AID - 10.1177/1740774508098326 [doi]
PST - ppublish
SO  - Clin Trials. 2008;5(6):607-16. doi: 10.1177/1740774508098326.