Summer 2010 Meetings

Clinical Advisory Committee | NGSP Steering Committee | Manufacturer Forum

2010 NGSP Clinical Advisory Committee Meeting

American Diabetes Association 70th Annual Scientific Sessions, June 2010

The CAC meeting was attended by representatives of various clinical diabetes organizations (e.g. IDF, ISPAD, ADA, EASD, NDEP, AADE).  The major topics of discussion were the recent recommendation to use HbA1c for the diagnosis of diabetes and pre-diabetes, tightening of the CAP HbA1c survey criteria, and point-of-care HbA1c testing.

NGSP Update
Randie Little, NGSP Network Coordinator, presented an update on NGSP activities.  She noted that the number of certified methods and laboratories continues to increase and that CAP surveys show that the variability of HbA1c results among methods and laboratories has been dramatically reduced since 1993.  The NGSP certification criteria for the 95% CI of the differences between a method and the NGSP were tightened from +/- 0.85% HbA1c to +/- 0.75% in January 2010.  The CAP began accuracy-based grading for HbA1c using NGSP-assigned target values in 2007 with an acceptable limit of +/-15%; this was subsequently reduced to +/- 12%, +/- 10% and +/- 8% in 2008, 2009 and 2010, respectively.  The CAP acceptable limit is likely to be reduced again for 2011.  Cumulative pass rates for the latest 2010A survey were >95% at all three HbA1c levels.  Interference from hemoglobin variants is still a concern but most laboratories are now using methods that show no interference from the most common variants (AS, AC, AE, AD).

Discussion:  There is evidence in the literature suggesting that iron-deficiency anemia may cause falsely-elevated HbA1c results.  The effect is likely minor and may be assay specific, further study is needed.  In some areas, particularly Southeast Asia, there is a significant prevalence of hemoglobin variants.   The possibility of reporting HbA1c results as a range that would take into account assay imprecision and other potential factors (race/ethnicity?, iron deficiency?) was discussed.  The advantage would be that it would make healthcare providers aware of the variability in results and enable them to utilize this knowledge when making treatment decisions.  It would also lead to demand for better assay methods.  However, there is the potential for confusion among healthcare providers and patients.  Also, given the differences in performance among methods and laboratories each lab would have to establish their own reporting range, which may not be practical.
CAP criteria for Proficiency Testing
David Sacks, NGSP Steering Committee Chair, announced that CAP will lower the acceptable limit for the GH-2 survey from the present +/- 8% to +/- 7% for 2011 and 2012.  The original plan was to lower the limit to +/- 6% but CAP decided that this was not feasible given the current state-of-the-art.  The criteria will be reconsidered for 2013, the question is: how accurate is accurate enough?

Point-of-care testing for HbA1c:  Is it good enough?
David Sacks outlined the current POC methods on the market and described the advantages and disadvantages of using these methods.  A recent study (Clin Chem 2010;56:44) showed that of 8 POC HbA1c methods, only two met acceptance criteria of total CV<3% and only one met current NGSP criteria with two different reagent lots.  The ADA decided to exclude POC methods from their recent recommendation to use HbA1c for diagnosis, saying that they are not accurate enough at this time.

Discussion:  POC HbA1c methods offer convenience and may be useful in some clinical settings.  However, their waived status means that end-users are not required to participate in proficiency testing and the vast majority do not, which is a major concern.  The recent recommendation to use HbA1c for diagnosing diabetes specifically excluded POC methods because they are not required to participate in PT and concerns regarding method performance.  However, performance is not equal among POC methods, several have demonstracted accuracy and imprecision comparable to laboratory analyzers.

FDA Recognition of Claims for using HbA1c for Diagnosis
David Sacks has spoken to the FDA, they will require manufacturers to submit a new 510K if they want to claim that their assay method can be used to diagnosis diabetes.  They will have to submit data showing how well their method performs at the recommended cutoff of 6.5% HbA1c, they have not yet developed specific criteria.

Use of HbA1c for Pre-Diabetes
Silvio Inzuchhi of Yale University presented the rationale for the ADA recommendation to use HbA1c to diagnose pre-diabetes using a cutoff of 5.7% HbA1c.  The ADA Workgroup on the Use of A1c for the Diagnosis of Diabetes and Identification of Pre-Diabetes found that there was significant discordance among the three measures of glycemia (FPG, 2-hour PG and HbA1c) in terms of subjects identified as having diabetes.   Numerous studies indicated that there was some increased risk of incident diabetes even below 6.0% HbA1c (the cutoff originally recommended by the International Expert Committee).  In the end the Workgroup decided to balance sensitivity and specificity and recommended a cutoff of 5.7%.

Discussion:  In practice technologies are often layered when diagnosing diabetes in that both HbA1c and glucose are used, especially in cases where results are close to cutoffs.  There is some controversy over whether it is appropriate to use the same HbA1c cutoff for all individuals.  Studies have shown ethnic and age differences but whether these are due to differences in glycemia or other factors is a topic of debate.

IFCC Working Group on HbA1c Standardization Update
David Sacks noted that the IFCC Working Group has been unexpectedly disbanded.  The IFCC Scientific Division stated that the group had achieved what it was established to do, which was to establish a reference system for HbA1c.  The IFCC lab network will continue under the Committee on Traceability in Laboratory Medicine.  In addition, the IFCC will establish an “Integrated Project” for HbA1c.  This group will be much smaller than the IFCC-WG and will function primarily as a scientific advisory body with the goal of having an interface between the IFCC and clinical users of HbA1c.

2010 Consensus Statement on the Worldwide Standardization of HbA1c Measurement
Ragnar Hanas presented the recommendations from the 2010 updated consensus statement (the original consensus statement was issued in 2007).  The recommendations are:

  1. HbA1c test results should be standardised worldwide, including the reference system and results reporting.
  2. The IFCC reference system for HbA1c represents the only valid anchor to implement standardisation of the measurement.
  3. HbA1c results are to be reported by clinical laboratories worldwide in SI (Système International) units (mmol/mol – no decimals) and derived NGSP units (% - one decimal), using the IFCC-NGSP master equation (DCCT units).
  4. HbA1c conversion tables including both SI (IFCC) and NGSP units should be easily accessible to the diabetes community.
  5. Editors of journals and other printed material are strongly recommended to require that submitted manuscripts report HbA1c in both SI (IFCC) and NGSP/DCCT units.
  6. The reportable term for glycated hemoglobin is HbA1c, although other abbreviations may be used in guidelines and educational material (A1C).
  7. The above consensus recommendations apply through 2011, when they will be discussed again at the next consensus meeting at the IDF meeting in Dubai December 2011.

In Sweden both IFCC and MonoS units will be reported beginning September 2010.  Beginning January 2011 only IFCC units will be reported to patients, both IFCC and DCCT/NGSP units will be reported to national registries.  Conversion tables will be made available to the diabetes community.

Discussion:  There is potential for confusion when trying to explain the change in numbers to patients that could adversely impact patient care.  However, in the UK dual numbers (IFCC and NGSP/DCCT) have been reported for over a year and they have not seen significant problems.  The U.S. will be reporting NGSP/DCCT numbers and some labs will report eAG as well, at this point there is no discussion of reporting IFCC numbers in the U.S.

Update on the New York City HbA1c Registry
Shadi Chamany described the current status of the NYC HbA1c registry.  The primary activities of the registry are to disseminate quarterly reports to healthcare providers, mail letters to patients at risk for complications, deliver and link resources to providers and patients, and surveillance and epidemiology.  The registry so far contains over 6 million test results on over 2 million individuals of all ages both with and without diabetes, and over 40,000 letters have been mailed out.  The program is evaluated by means of surveys of patients and healthcare providers as well as informal reports and inquiries.  So far there has been much positive feedback.  The program has not yet evaluated outcomes.