PMID- 27924815
OWN - NLM
STAT- MEDLINE
DCOM- 20171009
LR  - 20181113
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 31
IP  - 8
DP  - 2017 Aug
TI  - The relationship between eligibility criteria and adverse events in randomized 
      controlled trials of hematologic malignancies.
PG  - 1808-1815
LID - 10.1038/leu.2016.374 [doi]
AB  - To minimize adverse events (AEs) unrelated to drugs and maximize the likelihood 
      of drug approvals, eligibility criteria for randomized controlled trials (RCTs) 
      may be overly restrictive. The purpose of this study was to determine if RCTs in 
      hematologic malignancies exclude patients irrespective of known toxicities or 
      observed AEs. MEDLINE was searched from 1/2010 to 1/2015 for RCTs published in 
      high-impact journals. Of 97 trials, 33% were conducted in leukemia, 28% in 
      lymphoma, 34% in multiple myeloma and 5% in myelodysplastic syndromes or 
      myelofibrosis. Expected toxicities at thresholds of ⩾10%, ⩾5% and <5% were not 
      correlated with cardiac, hepatic or renal eligibility criteria (logistic 
      regression). To explore this lack of correlation we tested the concordance of 
      expected toxicities and eligibility criteria using a modified version of 
      McNemar's test: at each threshold, hepatic, renal and cardiac expected toxicities 
      were significantly discordant with eligibility criteria. Hepatic and renal 
      eligibility criteria were also not correlated with observed AEs, P=0.69 and 
      P=0.77, respectively, but a significant correlation was detected between cardiac 
      eligibility criteria and observed AEs, P=0.02. Thus, the analyzed RCTs excluding 
      patients with organ dysfunction do not reflect expected toxicities, based on 
      prescription drug labels/prior experience, or reported AEs on the trials.
FAU - Statler, A
AU  - Statler A
AD  - Leukemia Program, Department of Hematology and Medical Oncology, Cleveland 
      Clinic, Cleveland, OH, USA.
FAU - Radivoyevitch, T
AU  - Radivoyevitch T
AD  - Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
FAU - Siebenaller, C
AU  - Siebenaller C
AD  - Department of Pharmacy, Cleveland Clinic Taussig Cancer Institute, Cleveland 
      Clinic, Cleveland, OH, USA.
FAU - Gerds, A T
AU  - Gerds AT
AD  - Leukemia Program, Department of Hematology and Medical Oncology, Cleveland 
      Clinic, Cleveland, OH, USA.
FAU - Kalaycio, M
AU  - Kalaycio M
AD  - Leukemia Program, Department of Hematology and Medical Oncology, Cleveland 
      Clinic, Cleveland, OH, USA.
FAU - Kodish, E
AU  - Kodish E
AD  - Center for Ethics, Humanities and Spiritual Care, Cleveland Clinic, Cleveland, 
      OH, USA.
FAU - Mukherjee, S
AU  - Mukherjee S
AD  - Leukemia Program, Department of Hematology and Medical Oncology, Cleveland 
      Clinic, Cleveland, OH, USA.
FAU - Cheng, C
AU  - Cheng C
AD  - Department of Pharmacy, Cleveland Clinic Taussig Cancer Institute, Cleveland 
      Clinic, Cleveland, OH, USA.
FAU - Sekeres, M A
AU  - Sekeres MA
AD  - Leukemia Program, Department of Hematology and Medical Oncology, Cleveland 
      Clinic, Cleveland, OH, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161207
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Antineoplastic Agents/adverse effects
MH  - Heart/drug effects
MH  - Hematologic Neoplasms/*drug therapy
MH  - Humans
MH  - Kidney/drug effects
MH  - Liver/drug effects
MH  - Logistic Models
MH  - *Randomized Controlled Trials as Topic
EDAT- 2016/12/08 06:00
MHDA- 2017/10/11 06:00
CRDT- 2016/12/08 06:00
PHST- 2016/09/20 00:00 [received]
PHST- 2016/10/20 00:00 [revised]
PHST- 2016/11/02 00:00 [accepted]
PHST- 2016/12/08 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2016/12/08 06:00 [entrez]
AID - leu2016374 [pii]
AID - 10.1038/leu.2016.374 [doi]
PST - ppublish
SO  - Leukemia. 2017 Aug;31(8):1808-1815. doi: 10.1038/leu.2016.374. Epub 2016 Dec 7.