Review of Endocrinology Guidelines
Decision-makers frequently rely on the body of pertinent research in making decisions regarding clinical management decisions. The goal is to critically appraise and synthesize the evidence before making recommendations, developing protocols and making other decisions. Serious attention is paid to the validity of the primary studies to determine reliability before accepting them into the review. Brito and colleagues have described the rigor of systematic reviews (SRs) cited from 2006 until January 2012 in support of the clinical practice guidelines put forth by the Endocrine Society using the Assessment of Multiple Systematic Reviews (AMSTAR) tool .
The authors included 69 of 2817 studies. These 69 SRs had a mean AMSTAR score of 6.4 (standard deviation, 2.5) of a maximum score of 11, with scores improving over time. Thirty five percent of the included SRs were of low-quality (methodological AMSTAR score 1 or 2 of 5, and were cited in 24 different recommendations). These low quality SRs were the main evidentiary support for five recommendations, of which only one acknowledged the quality of SRs.
The authors conclude that few recommendations in field of endocrinology are supported by reliable SRs and that the quality of the endocrinology SRs is suboptimal and is currently not being addressed by guideline developers. SRs should reliably represent the body of relevant evidence. The authors urge authors and journal editors to pay attention to bias and adequate reporting.
Delfini note: Once again we see a review of guideline work which suggests using caution in accepting clinical recommendations without critical appraisal of the evidence and knowing the strength of the evidence supporting clinical recommendations.
1. Brito JP, Tsapas A, Griebeler ML, Wang Z, Prutsky GJ, Domecq JP, Murad MH, Montori VM. Systematic reviews supporting practice guideline recommendations lack protection against bias. J Clin Epidemiol. 2013 Jun;66(6):633-8. doi: 10.1016/j.jclinepi.2013.01.008. Epub 2013 Mar 16. PubMed PMID: 23510557.
Review of Bias In Diabetes Randomized Controlled Trials
Healthcare professionals must evaluate the internal validity of randomized controlled trials (RCTs) as a first step in the process of considering the application of clinical findings (results) for particular patients. Bias has been repeatedly shown to increase the likelihood of distorted study results, frequently favoring the intervention.
Readers may be interested in a new systematic review of diabetes RCTs. Risk of bias (low, unclear or high) was assessed in 142 trials using the Cochrane Risk of Bias Tool. Overall, 69 trials (49%) had at least one out of seven domains with high risk of bias. Inadequate reporting frequently hampered the risk of bias assessment: the method of producing the allocation sequence was unclear in 82 trials (58%) and allocation concealment was unclear in 78 trials (55%). There were no significant reductions in the proportion of studies at high risk of bias over time nor in the adequacy of reporting of risk of bias domains. The authors conclude that these trials have serious limitations that put the findings in question and therefore inhibit evidence-based quality improvement (QI). There is a need to limit the potential for bias when conducting QI trials and improve the quality of reporting of QI trials so that stakeholders have adequate evidence for implementation. The entire freely-available study is available at—
Ivers NM, Tricco AC, Taljaard M, Halperin I, Turner L, Moher D, Grimshaw JM. Quality improvement needed in quality improvement randomised trials: systematic review of interventions to improve care in diabetes. BMJ Open. 2013 Apr 9;3(4). doi:pii: e002727. 10.1136/bmjopen-2013-002727. Print 2013. PubMed PMID: 23576000.
A Performance Measure for Overuse? The Loosening Of Tight Control In Diabetes
Performance measures for tighter glycemic control appeared following the DCCT trial (Type 1 diabetes) in 1993 and the UKPDS trial (type 2 diabetes) in 1998., About 7 years ago groups recommended that glycohemoglobin concentrations be less than 7%, even though clear evidence of improved net outcomes was lacking.
Now in an editorial in the online version of Archives of Internal Medicine, Pogach and Aron have nicely summarized details of this journey into overuse of hypoglycemic agents resulting in the problem of harms probably outweighing benefits—at least for some diabetics—in an editorial entitled, The Other Side of Quality Improvement in Diabetes for Seniors: A Proposal for an Overtreatment Glycemic Measure.
The authors review the ACCORD, ADVANCE and VADT trials and remind readers that tight glycemic control did not yield cardiovascular benefits in these trials and that severe hypoglycemia occurred in the intensive treatment groups of all three trials. Of concern was the finding that ACCORD was terminated early because of increased mortality in the intensive glycemic treatment group. These trials appear to have increased concern about the risks of severe hypoglycemia in elderly patients and patients with existing cardiovascular disease, and the National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set (HEDIS) modified its glycohemoglobin goal to less than 7% for persons younger than 65 years without cardiovascular disease or end-stage complications and diabetes and established a new, more relaxed goal of less than 8% for persons 65 to 74 years of age.
Kirsh and Aron took this a step further in 2011 and proposed a glycohemoglobin concentration of less than 7.0% as a threshold measure of potential overtreatment of hyperglycemia in persons older than 65 years who are at high risk for hypoglycemia. They point out that the risk for hypoglycemia could be assessed by utilizing data from the electronic medical record regarding prescriptions for insulin and/or sulfonylurea medications and retrieving information on comorbidities such as chronic kidney disease, cognitive impairment or dementia, neurologic conditions that may interfere with a successful response to a hypoglycemic event.
This commentary is worth reading and thinking about. We agree with them that the time has come to take more actions to prevent the risk of possible overtreatment in diabetes.
 The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 Sep 30;329(14):977-86. PubMed PMID: 8366922.
 Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. Erratum in: Lancet 1998 Nov 7;352(9139):1558. PubMed PMID: 9742977.
 Pogach L, Aron DC. Sudden acceleration of diabetes quality measures. JAMA. 2011 Feb 16;305(7):709-10. PubMed PMID: 21325188.
 Published Online: September 10, 2012. doi:10.1001/archinternmed.2012.4392.
 Kirsh SR, Aron DC. Choosing targets for glycaemia, blood pressure and low-density lipoprotein cholesterol in elderly individuals with diabetes mellitus. Drugs Aging. 2011 Dec 1;28(12):945-60. doi: 10.2165/11594750-000000000-00000. PubMed PMID: 22117094.