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Chow SC, Chang M. Adaptive design methods in clinical trials - a review. Orphanet J Rare Dis. 2008 May 2;3:11. Review. PMID: 18454853

Shein-Chung Chow of Duke University School of Medicine and Mark Chang of Millennium Pharmaceuticals have written an excellent review article about adaptive design in clinical trials, focusing on research in rare diseases, multiple myeloma and non-Hodgkin’s lymphoma.

So what is adaptive design? From the paper:

"In clinical trials, it is not uncommon to modify trial and/or statistical procedures during the conduct of clinical trials based on the review of interim data. The purpose is not only to efficiently identify clinical benefits of the test treatment under investigation, but also to increase the probability of success of clinical development. Trial procedures are referred to as the eligibility criteria, study dose, treatment duration, study endpoints, laboratory testing procedures, diagnostic procedures, criteria for evaluability, and assessment of clinical responses. Statistical procedures include randomization, study design, study objectives/hypotheses, sample size, data monitoring and interim analysis, statistical analysis plan, and/or methods for data analysis. In this article, we will refer to the adaptations (or modifications) made to the trial and/or statistical procedures as the adaptive design methods. Thus, an adaptive design is defined as a design that allows adaptations to trial and/or statistical procedures of the trial after its initiation without undermining the validity and integrity of the trial."

Adaptive design fits well with translational research, as it makes it possible to reflect real-time clinical experience in a clinical trial. Chow and Chang also present the problematic aspects of adaptive design, and in the end could help investigators employ adaptive design to optimize development of new therapies for hard-to-treat cancers and other challenging diseases.

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

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Lichtman MA. Battling the hematological malignancies: the 200 years’ war. Oncologist. 2008 Feb;13(2):126-38. PMID: 18305057

A clearly written historical review and perspective on current research by Marshall Lichtman of the University of Rochester Medical Center.

Professor Marshall applies a systems approach to drug development, employing a nuanced interpretation of the imatinib (Glivec) story as a case study:

"When one has stratified the blood cancers into phenotypes and genotypes, the number of patients amenable to a specific oncogene- or oncoprotein-targeted therapy becomes relatively small. This situation is unattractive for pharmaceutical companies that may need to invest hundreds of millions of dollars into the effort to develop a drug. For a pharmaceutical company, the greater the specificity of the drug, the fewer the number of future users. Today, most drugs can be used for several blood cancers and for cancers of other tissues. To move to more focused and, presumably, more effective and less toxic drugs, collaboration among governmental agencies, such as the National Institutes of Health, the pharmaceutical and biotechnology industries, and academic health centers (research-intensive medical schools, research institutes, research hospitals) needs to be further enhanced.

"There are incentives for companies to pursue drugs with an apparently small market. For example, the development of imatinib mesylate may have done more than advance the treatment of CML; it may have caused pharmaceutical companies to have second thoughts about developing new drugs for uncommon cancers. The pharmaceutical company involved (Ciba-Geigy, later Novartis) was looking for a drug to block a tyrosine kinase (platelet-derived growth factor receptor) potentially involved in atherosclerosis, a very large market, but was forced to aggressively manufacture imatinib mesylate because of the demands of patients with CML, a very small market, and in the end did (very) well by doing good, because of pricing, because of the fact that the drug is required indefinitely, and because of the drug’s ability to cause the remission of a gastrointestinal stromal tumor, which effectively doubled the target patient population. The latter event is another example of how drug development in the hematological malignancies continues to provide the path to therapy of other types of cancer."

OncologyWatch: Posts about free-access articles on aspects of oncology theory, practice and policy (about the blogger). This blog is not a source for medical advice.

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Martin S, Ulrich C, Munsell M, et al. Delays in cancer diagnosis in underinsured young adults and older adolescents. Oncologist. 2007 Jul;12(7):816-24. PMID: 17673613

An important study with evidence that young people in the U.S. are likely to have a delay in cancer diagnosis because of inadequate health insurance, with consequent presentation of advanced stages of disease. From the introduction:

"Despite the advances in cancer diagnosis and treatment, older adolescents and young adults with cancer in the U.S., especially those in the 20–39 years age group, have not experienced the same survival prolongation or mortality reduction as their older and younger counterparts. Reasons for the failure to improve survival in this cohort may be related to delays in diagnosis, which are known to occur more frequently in cancer patients in this age group than in others. Also, the 18–24 years age group is both the most underinsured in the U.S. as well as the least likely to access health care, and the 25–34 years age group is the next most uninsured age group. The hypothesis of this study, therefore, was that a lack of health insurance is associated with delay in diagnosis in this age group." 

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