pharmacogenomics evidence/clinical relevance schemes (was Re: Minutes from Clinical Decision Support teleconference)

On 04/27/2012 06:40 AM, Matthias Samwald wrote:
> There exist some evidence classification schemes in the 
> pharmacogenomics domain (e.g. from PharmGKB, of course). I documented 
> the PharmGKB schemes at 
> https://docs.google.com/spreadsheet/pub?hl=en_US&key=0AiGT-vnkGcoLdFFVMEdqcFdYaDFqS0xHTnlUT0N3cEE&hl=en_US&gid=1 
> <https://docs.google.com/spreadsheet/pub?hl=en_US&key=0AiGT-vnkGcoLdFFVMEdqcFdYaDFqS0xHTnlUT0N3cEE&hl=en_US&gid=1> (values 
> in the decision table are auto-completed based on the entities there). 
> I guess for this project we should standardize to using a single 
> scale, rather than mixing different scales.
> *TODO:* Would you (or someone else) be interested in looking into 
> these classification schemes to see what would fit best? Are some of 
> these schemes available as ontologies, e.g. via BioPortal? However, I 
> guess we should at least retain some compatibility with PharmGKB, CPIC 
> and other such initiatives!
I searched for the DPWG evidence/clinical relevance scheme 
<http://www.pharmgkb.org/home/dutch_pharmacogenetics_working_group.jsp> 
in Bioportal and did not find any results.

The CPIC scheme covers level of evidence and the strength of a consensus 
recommendation on dosage adjustment (see below, and 
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098762/?tool=pubmed>) . 
This scheme appears to be used in all of the guidelines here 
<http://www.pharmgkb.org/cpic.jsp>. I also do not see anything in 
Bioportal.

In terms of "best fit", I would argue that it would be best to *not* try 
and map all recommendations to one scheme because the recommendations 
are to some extent subjective to the party that assigns them. For 
example, CPIC appears to assign a high level of evidence to in vitro  
experiments in its clopidogrel guidelines (see supplemental table S6 in 
http://www.pharmgkb.org/download.action?filename=cpic-cyp2c19-clopidogrel-supplement.pdf). 
However, DPWG requires in vivo trials for its highest ratings.

It might be best to keep the ratings as assigned by the group developing 
the guidelines but just be explicit about the source and meaning, 
perhaps by developing "evidence rating scheme", "clinical significance 
rating scheme", and "strength of recommendation rating scheme" types. 
Each type having a predicate that identifies the expert consensus source 
of the rating scheme, the codes for the rating scheme, which code is 
considered the lowest rating, and descriptions/definitions for each 
rating level. Anyways, more to discuss than can be included in this 
email.....

Another issue to always keep in mind is mentioned in the following quote 
from <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098762/?tool=pubmed>:

"Although some pharmacogenetic cases may have level 3 evidence [the 
highest], other considerations may affect the recommendations, such as 
the  potential preventable burden of disease or morbidity, potential 
harm of intervention, and current practice,^10 
<http://www.ncbi.nlm.nih.gov/pubmed/19189910> as exemplified by the use 
of warfarin in the presence of /CYP2D9/ and /VKORC1/."

As an aside, it might make sense for these evidence and clinical 
relevance schemes to eventually be integrated into SO-PHARM 
<http://bioportal.bioontology.org/ontologies/1061>.

hope it helps -Rich

*CPIC pharmacogenomics evidence/clinical relevance scheme:*

"Levels of Evidence Linking Genotype to Phenotype
Based on previously published criteria (42), a simple scale of high, 
moderate, or weak to grade
the levels of evidence was chosen:
. High: Evidence includes consistent results from well-designed, 
well-conducted studies.
. Moderate: Evidence is sufficient to determine effects, but the 
strength of the evidence is
limited by the number, quality, or consistency of the individual 
studies; generalizability
to routine practice; or indirect nature of the evidence.
. Weak: Evidence is insufficient to assess the effects on health 
outcomes because of
limited number or power of studies, important flaws in their design or 
conduct, gaps in
the chain of evidence, or lack of information."

"Overall, the therapeutic recommendations are simplified to allow rapid 
interpretation by
clinicians. They have been adopted from the rating scale for 
evidence-based therapeutic
recommendations on the use of retroviral agents.
A: Strong recommendation for the statement
B: Moderate recommendation for the statement
C: Optional recommendation for the statement"


-- 
Richard Boyce, PhD
Assistant Professor of Biomedical Informatics
Scholar, Comparative Effectiveness Research Program
University of Pittsburgh
rdb20@pitt.edu
412-648-6768