Randomised Controlled Trials (RCTs) are considered the ‘gold standard’ research method for assessing new medical treatments. But research published in BioMed Central’s open access journal Trials shows that the design of a remarkable 93 percent of 2235 so-called RCTs published in some Chinese medical journals during 1994 to 2005 was flawed, casting doubt on the reliability of research that is likely to influence medical decision-makers.

Researchers led by Taixiang Wu of the Chinese Cochrane Centre at Sichuan University, China and Ottawa Hospital Research Institute investigated clinical trials published in China between 1994 and 2005, searching the China National Knowledge Infrastructure (CNKI) electronic database for RCTs on 20 common diseases. To determine how many of these met recognised standards for randomly allocating participants to treatment groups, trained investigators interviewed the first or co-authors of 2235 trial reports by phone.

Less than seven percent of self-described RCTs published in some Chinese medical journals meet criteria for authentic randomisation. The researchers looked at both conventional and traditional Chinese medicine trials, but there was no difference between these in terms of study authenticity rates. However, all RCTs of pre-market drug clinical trial were authentic, and RCTs conducted at hospitals affiliated with medical universities were more likely to be authentic than trials conducted at lower tier level three and level two hospitals. More than half of the trials at university-affiliated hospitals met RCT criteria, which means lower-tier hospital research is the least rigorous in design terms.

“The fact that so many non-RCTs were published as RCTs reflected that peer-review needs to be improved and a Good Practice of Peer Review, including how to identify the authenticity of the study, urgently needs to be developed,” says Wu.

Misleading reporting of medical research is not unique to China. Studies labelled as RCTs are more likely to influence health policy-makers meaning falsely reported RCTs have the potential to mislead health care providers, consumers and policy-makers. The results of this study suggest authors of systematic reviews - articles that combine the results of multiple RCTs - need to be aware that RCTs in some Chinese journals may not be RCTs at all.

The approximately 1100 medical journals now active in China are rapidly increasing their output of research reports, including many identified by their authors as RCTs. But these trials present mostly positive results (they favour the treatment being investigated), which can be influenced by inadequate randomisation of patients when designing the study.

Notes:

1. Randomized trials published in some Chinese journals: How many are randomized?
Taixiang Wu, Youping Li, Zhaoxiang Bian, Guanjian Liu and David Moher
Trials (in press)

http://www.trialsjournal.com/

Source:
Charlotte Webber

BioMed Central

New research describes a molecular tool that shows great promise as a therapeutic for human acute myeloid leukemia (AML), a notoriously treatment-resistant blood cancer. The study, published by Cell Press in the July 2nd issue of the journal Cell Stem Cell, describes exciting preclinical studies in which a new therapeutic approach selectively attacks human cancer cells grown in the lab and in animal models of leukemia.

AML is a cancer of the white blood cells that has an extremely poor prognosis and does not respond well to conventional chemotherapy. “The cellular and molecular basis for this dismal picture is unclear,” offers senior study author Associate Professor Richard Lock from the Children’s Cancer Institute Australia and the University of New South Wales. “However, previous research has suggested that leukemia stem cells (LSCs) may lie at the heart of post-treatment relapse and chemoresistance.” LSCs are cells that can initiate AML and are critical for its long-term growth.

Associate Professor Lock and colleagues exploited the fact that the molecule CD123 is expressed at very high levels on LSCs but not on normal blood cells. CD123 is part of the interleukin-3 receptor, a protein that interacts with a growth factor (called a cytokine) that influences cell survival and proliferation. The researchers created a therapeutic antibody that recognized and bound to CD123 with the hope that this antibody would selectively interfere with AML-LSC survival.

When AML-LSCs from human patients were transplanted into mice treated with the antibody, called 7G3, cytokine signaling in the tumor cells was blocked. Further, 7G3 impaired migration of the AML-LSCs to bone marrow and activated the innate immune system of the host mouse to destroy the AML-LSCs. Overall, treatment with 7G3 substantially improved mouse survival when compared with control groups. The researchers go on to report that a CD123-targeting antibody is currently being used in phase 1 clinical trials of advanced AML and that there are no signs of treatment-related toxicity.

These results hold substantial promise for future cancer therapeutics. “The recent characterization of defined populations of cancer stem cells in a range of human malignancies, as well as their relative resistance to conventional chemotherapy and radiotherapy, supports the broad applicability of our approach and provides rationale for the progression of AML-LSC-targeted therapeutics from preclinical evaluation to clinical trials,” concludes Associate Professor Lock.

The researchers include Liqing Jin, University Health Network, Toronto, Canada; Erwin M. Lee, University of New South Wales, Sydney, Australia; Hayley S. Ramshaw, Centre for Cancer Biology, Adelaide, Australia; Samantha J. Busfield, CSL Limited, Melbourne, Australia; Armando G. Peoppl, University Health Network, Toronto, Canada; Lucy Wilkinson, Queensland Institute of Medical Research, Brisbane, Australia; Mark A. Guthridge, Centre for Cancer Biology, Adelaide, Australia; Daniel Thomas, Centre for Cancer Biology, Adelaide, Australia; Emma F. Barry, Centre for Cancer Biology, Adelaide, Australia; Andrew Boyd, Queensland Institute of Medical Research, Brisbane, Australia; David P. Gearing, CSL Limited, Melbourne, Australia; Gino Vairo, CSL Limited, Melbourne, Australia; Angel F. Lopez, Centre for Cancer Biology, Adelaide, Australia; John E. Dick, University Health Network, Toronto, Canada; and Richard B. Lock, University of New South Wales, Sydney, Australia.

Source:
Cathleen Genova

Cell Press

MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX) today announced that the Company has submitted an application for the authorization of a phase 1b/2a clinical study in patients with active rheumatoid arthritis (RA) for its lead drug MOR103, a fully human HuCAL-derived monoclonal antibody directed against Granulocyte Macrophage-Colony Stimulating Factor. The trial, which will be conducted in multiple centers in several European countries, is expected to enroll 135 patients in total beginning in the second half of 2009. Additionally, the Company today reported positive results from the phase 1 clinical study for MOR103 in healthy volunteers. The results of this study indicate that MOR103 is generally safe and well tolerated at all doses administered.

“We are pleased to advance the clinical development of this promising compound into a phase 1b/2a clinical trial to further evaluate safety and tolerability as well as clinical activity in RA patients,” commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys. “In combination with the attractive preclinical profile the results we have seen in the phase 1 trial support our plans to develop MOR103 as a safe and efficacious drug for the treatment of inflammatory disorders. In addition to the excellent characteristics the antibody has shown so far with regard to affinity, specificity and stability, we have been able to demonstrate a robust serum half-life in humans.”

The completed phase 1 trial was designed as a randomized, double-blind, placebo controlled single ascending dose study to assess the safety, tolerability and pharmacokinetic parameters of MOR103 in healthy volunteers. In total, 63 volunteers received ascending doses of MOR103 up to a concentration of 3 mg/kg or placebo in seven dose cohorts via intravenous infusion. No maximum tolerated dose (MTD) was reached in the study. Analysis of the pharmacokinetic properties of MOR103 showed a serum half-life typical of a fully human antibody which could translate into a competitive dosing regimen. The overall safety, tolerability and pharmacokinetic properties of MOR103 provide a solid foundation for the Company’s development plans, including the forthcoming Phase 1b/2a study in patients.

MorphoSys will present at today’s 4th Annual Piper Jaffray Europe Conference at 08:30 am BST (09:30 am CET). The presentation as well as live and archived webcast of the presentation will be provided at http://www.morphosys.com.

Source
MorphoSys AG