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e206 Diabetes Care Volume 37, September 2014

RESPONSE TO COMMENTS ON ZHANG ET AL. Yuanhui Zhang,1 Rozalina G. McCoy,2

Jennifer E. Mason,3 Steven A. Smith,2,4
Second-Line Agents for Glycemic Control Nilay D. Shah,4,5 and Brian T. Denton6

for Type 2 Diabetes: Are Newer Agents

Better? Diabetes Care 2014;37:13381345
Diabetes Care 2014;37:e206e207 | DOI: 10.2337/dc14-1339

We are grateful for the comments from Bae et al. question an apparent as- similar or decreased treatment effects
Messori and Bellia (1) and those of Bae sumption in our model that underlying for the newer medications. Bae et al.
et al. (2) regarding our article (3). We HbA1c uctuation at baseline remains also suggested the use of propensity
hope the following response will clarify constant throughout the patients life score methods to account for possible
the questions they raised. (2). However, we did not assume a con- confounding. This would be interesting
Messori and Bellia (1) pointed out stant baseline; we assumed a linear to explore in theory, but in practice
that the incremental cost-effectiveness increasing trend in HbA1c, consistent there are likely a number of unmea-
ratio (ICER) is preferred over the abso- with other published glycemic control sured confounders. Fortunately, our
lute cost-effectiveness ratio. We agree, models (4,5). sensitivity analysis based on RCT esti-
and it is worth noting that Fig. 1 in our Bae et al. suggested the use of treat- mates obviates all of these concerns.
article provides complete details about ment effect estimates, based on real- Bae et al. fairly criticize the fact that
the expected quality-adjusted life-years world data, is a major limitation. We the cost of hypoglycemia was not in-
(QALYs) prior to rst events and the ex- take the contrary perspective, i.e., that cluded in the model. As they pointed
pected medication costs under all treat- this is a strength of our study, as real- out, we adjusted for hypoglycemia out-
ment regiments. As such, it subsumes world data accounts for potential lack of comes, but not for cost. The source they
ICER estimates. Admittedly, the readers adherence and other behavioral factors cite provides an estimate of the cost of
must calculate them from the graph and that may not be present in the ideal set- hypoglycemia hospitalization of $17,564
therefore we provide the estimates for ting of a randomized controlled trial per event for an inpatient admission,
the glycemic control goal of HbA1c ,7% (RCT). Of course, we also recognize the $1,387 for an emergency department
here. For males, for regimens T1-T4 the merit of RCTs in limiting bias, and for this visit, and $394 for an outpatient visit.
ICERs in units of $/QALY are 10,369, reason we reported results based on The source also provides overall inci-

11,062, 11,277, 11,144, respectively. For treatment effects reported in RCTs. As dence rates for each event type. The
females, for regimens T1-T4 the ICERs are readers can see from our results, these estimated time frame for the newer
9,310, 9,865, 10,043, 9,933, respectively. do not change our main conclusions. medications, from Table 2 of our article,
Messori and Bellia also express confu- Bae et al. propose the use of a longer was 1.59 to 2.76 years. Using the upper
sion over the computation of life-years time window for measuring the effect of bound of 2.76 years as an estimate of
to rst event. To clarify, our reported medications. In our analysis, we found the time on medication, the total aver-
results are based on a median diagnosis no evidence that a longer time window age cost per patient due to hypoglyce-
age between 54 and 55 years. The life- would make a signicant difference. mia is conservatively estimated at $89.
years to rst event are the sum of time to Compared with the 3-month time win- Assuming all events are attributed to
diagnosis and the time from diagnosis to dow used in our article, the use of 6- and sulfonylurea and none to the newer
rst event, where the latter is computed 12-month time windows before and medications, this estimate would not
using our model. after treatment initiation resulted in change any of our conclusions.

Graduate Program in Operations Research, North Carolina State University, Raleigh, NC
Division of Endocrinology, Department of Internal Medicine, Mayo Clinic, Rochester, MN
Department of Public Health Sciences, University of Virginia, Charlottesville, VA
Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN
Optum Labs, Cambridge, MA
Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI
Corresponding author: Brian T. Denton,
2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for prot,
and the work is not altered. Zhang and Associates e207

Bae et al. also cite a recent source sug- of our study to provide a better under- 3. Zhang Y, McCoy RG, Mason JE, Smith SA, Shah
gesting an average cost of $127 per person standing of our results and conclusions. ND, Denton BT. Second-line agents for glycemic
control for type 2 diabetes: are newer agents
per event for nonsevere hypoglycemic better? Diabetes Care 2014;37:13381345
events (6). However, Brod et al. (6) studied 4. CDC Diabetes Cost-effectiveness Group.
both type 1 and type 2 diabetes. In their Duality of Interest. No potential conicts of Cost-effectiveness of intensive glycemic con-
study, 74% of patients reported using interest relevant to this article were reported. trol, intensied hypertension control, and se-
rum cholesterol level reduction for type 2
insulin and patients on oral medications diabetes. JAMA 2002;287:25422551
reported a lower impact on work pro- References 5. Chen J, Alemao E, Yin D, Cook J. Development
ductivity and less work absenteeism, 1. Messori A, Bellia A. Comment on Zhang et al. of a diabetes treatment simulation model: with
Second-line agents for glycemic control for type application to assessing alternative treatment in-
which were the primary factors attrib-
2 diabetes: are newer agents better? Diabetes tensication strategies on survival and diabetes-
uted to the cost of nonsevere hypogly- Care 2014;37:13381345 (Letter). Diabetes related complications. Diabetes Obes Metab
cemia events. Care 2014;37:e205. DOI: 10.2337/dc14-0983 2008;10(Suppl. 1):3342
In summary, none of the concerns 2. Bae J, Curtis BH, Kendall DM, Heine RJ. Comment 6. Brod M, Wolden M, Christensen T, Bushnell DM.
on Zhang et al. Second-line agents for glycemic con- Understanding the economic burden of nonsevere
raised change the conclusions reported
trol for type 2 diabetes: are newer agents better? nocturnal hypoglycemic events: impact on work
in our article. We appreciate the oppor- Diabetes Care 2014;37:13381345 (Letter). Diabe- productivity, disease management, and resource
tunity to elaborate on these aspects tes Care 2014;37:e204. DOI: 10.2337/dc14-1041 utilization. Value Health 2013;16:11401149