Friday, February 28, 2014

CPIC abacavir & HLA-B guideline update published

CPIC has extensively reviewed the literature and concluded no changes are required to the therapeutic recommendations of the abacavir dosing guideline based on HLA-B genotype since the original publication in 2012.

The 2014 update includes the following additions:
  • Clinical implementation resources to help implementation of the guidelines into an Electronic Heath Record (EHR), including design of clinical decision support (CDS) alerts. 
  • Abacavir recommendations based on HLA-B*57:01 in pediatrics.
  • Additional supporting studies.
  • Discussion on recent studies regarding the mechanism of abacavir-induced hypersensitivity in HLA-B*57:01 individuals. 
View the interactive CPIC abacavir dosing guidelines based on HLA-B genotype, with the available full update and original published guidelines.

Read the article:
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update.
Michael A. Martin, James M. Hoffman, Robert R. Freimuth, Teri E. Klein, Betty J. Dong, Munir Pirmohamed, J. Kevin Hicks, Mark R. Wilkinson, David W. Haas and Deanna L. Kroetz. Clinical Pharmacology & Therapeutics accepted article preview online 21 February 2014; doi:10.1038/clpt.2014.38

Tuesday, February 18, 2014

The Uncertain Future of Genetic Testing

In an opinion piece from authors at the Stanford Center for Law and the Biosciences, the future of genetic testing is discussed. 

After a warning letter from the FDA, 23andMe had to halt their service that provided direct-to-consumer health interpretation of SNP chip results (though they still provide the raw data and ancestry information). Something “intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease” is regarded as a device by the FDA. 23andMe had marketed their Personal Genome Service product, which involved a spit kit, as “the first step in prevention” and “toward mitigating serious diseases” (see letter). However, it was not approved as a device, and as the company had failed to provide adequate information regarding analytical and clinical validity, the FDA required discontinuation of the product. Had the kit been ordered via a doctor from a lab that used the same tests, action may not have been taken. 

One major problem is that no defined guidelines on the regulation for genetic testing are available; a kit by Illumina has been approved without the need to demonstrate clinical validity. The authors discuss how the FDA have continued to delay announcing a proposed policy for the regulation for genetic tests, reflecting the difficulty in determining the clinical validity of these tests (in particular for variants with weak effects or unknown significance). The interpretation of the effect of SNP risk alleles on health can vary markedly. Another concern of direct-to-consumer genetics is the interpretation of the results by the consumer and possible medical interventions they may subsequently undertake without medical expert advice. 

An even more difficult scenario for establishing regulatory rules comes as the era of whole genome/exome sequencing technology takes over SNP chips. Regulation needs to be a fine balance between halting genetic testing altogether by requiring clinical validity for every single variant, and preventing “quacks” from selling their wares. 

Read the opinion piece: 
23andMe, the Food and Drug Administration, and the Future of Genetic Testing. Patricia J. Zettler, JD; Jacob S. Sherkow, JD; Henry T. Greely, JD. JAMA Intern Med. Published online February 17, 2014. 

Thursday, February 6, 2014

CPIC Publishes Their Guideline Development Process

In Current Drug Metabolism, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has defined the standardized operating procedures undertaken for each guideline written. Outlined in the publication is how gene-drug relationships are initially assessed for a potential guideline, how a writing committee with experts in the subject is established, the gathering and grading of evidence linking a genotype to drug response and the development of a therapeutic recommendation. The standard format of a CPIC guideline paper and the process of evaluation by the CPIC steering committee is also defined.

In the article, CPIC guidelines are compared and evaluated against the Institute Of Medicine's (IOM's) standards for developing trustworthy clinical practice guidelines, from establishing transparency to updating.

All CPIC guidelines and updates are posted on PharmGKB in an interactive format. The CPIC Informatics working group is developing methods to enable integration and implementation of CPIC guidelines into electronic medical systems.  

> View all CPIC dosing guidelines
> View the list of CPIC guideline gene-drug pairs that have been published or are in progress.
> View all CPIC publications

Read the article:
Incorporation of Pharmacogenomics into Routine Clinical Practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process.
Kelly E. Caudle, Teri E. Klein, James M. Hoffman, Daniel J. Müller, Michelle Whirl-Carrillo, Li Gong, Ellen M. McDonagh, Katrin Sangkuhl, Caroline F. Thorn, Matthias Schwab, JosĂ© A.G. AgĂșndez, Robert R. Freimuth, Vojtech Huser, Ming Ta Michael Lee, Otito F. Iwuchukwu, Kristine R. Crews, Stuart A. Scott, Mia Wadelius, Jesse J. Swen, Rachel F. Tyndale, C. Michael Stein, Dan Roden, Mary V. Relling, Marc S. Williams and Samuel G. Johnson.
Current Drug Metabolism (2014) Jan 30. [Epub ahead of print, PMID:24479687].