Thursday, October 9, 2008

Translational research for medical interventions

Tracking the lag between promise and payoff by Janet D. Stemwedel, Adventures in Ethics and Science, October 2, 2008. This blog post isn't about cancer stem cells, but is of interest because it's focus is on translational research for medical interventions. Excerpts:
One of the reasons non-scientists see science as at all valuable is that scientific research may result in useful medical treatments. And one of the aspects of science that seems elusive to non-scientists is just how long it can take scientific research to bring those useful medical treatments about.
.....
The time interval between the first report on preparation, isolation, or synthesis (or the earliest patent) and the highly cited articles reporting successful clinical interventions -- between the report of findings with clinical potential and the determination via clinical trials that that promise is realized in a treatment -- is the "translational lag". (There is, of course, another lag that's harder to quantify this way -- that between the initial findings in the research lab and the publication of those findings.)
Contopoulos-Ioannidis et al. found that the median translational lag for the highly cited article[s] in their study was 24 years. That's a long time.
The blog post is based on this article: Life Cycle of Translational Research for Medical Interventions, by Despina G. Contopoulos-Ioannidis, George A. Alexiou, Theodore C. Gouvias, John P. A. Ioannidis, Science 2008(Sep 5); 321(5894): 1298-9 [PubMed Citation]. The article isn't freely accessible, and has no abstract. The brief Summary:
From the initial discovery of a medical intervention to a highly cited article is a long road, and even this is not the end of the journey.
An excerpt from the final section of the full text:
The following are some recommendations for improving the system, based on our analyses:
• Discovery of new substances and interventions remains essential, but proper credit and incentives should be given to accelerate the testing of these applications in high-quality, unbiased clinical research and the replication of claims for effectiveness.
• Multidisciplinary collaboration with focused targets and involving both basic and clinical sciences should be encouraged.
• Proof of effectiveness for new interventions requires large, robust randomized clinical trials.
• Translational efforts for common diseases should focus more on novel agents and new cutting-edge technologies; for these ailments, it is unlikely that genuine major benefits from interventions already known for a long time have gone unnoticed.
Comments: Of the 32 interventions highlighted in this study, only two were cancer-related:

1) Levamisole (with Fluorouracil): Colon cancer
• Date of highly cited study: 1990
• Date of first description of intervention: 1966
• Report of first human use: 1977
2) Tamoxifen: Breast cancer prevention
• Date of highly cited study: 1998
• Date of first description of intervention: 1964
• Report of first human use: 1971
For cancer stem cells, what might be an important first intervention to be described? Proof that the eradication of cancer stem cells from a patient's tumor is therapeutic?

Perhaps a clinical demonstration that cancer stem cells can be used as a prognostic indicator of disease progression wouldn't be regarded as a "therapeutic intervention", but it's a key challenge for those doing research on cancer stem cells. See, for example, a review by Eric Lagasse, Gene Ther 2008(Jan); 15(2): 136-42 [PubMed Abstract]. Excerpt from the full text (not freely accessible):
[Remaining challenges] include the clinical demonstration that cancer stem cells can be used as a prognostic indicator of disease progression and proof that the eradication of cancer stem cells from a patient's tumor is therapeutic.

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