The ACCORD trial included HRQL as a secondary objective to more fully understand the potential benefits of intensive glycemic control through the patient’s point of view. After baseline HRQL status and clinical covariates in repeated-measures analysis were controlled, the results obtained for change in HRQL over a 48-month observation period after randomization did not show meaningful benefit between intensive glycemic control as compared with standard glycemic control strategies in domains of general health, diabetes symptoms, or depression. The pattern of no intensive treatment benefit on HRQL is consistent with the results for the ACCORD main study (1
) of lack of cardiovascular benefit from intensive glycemia treatment with a target of HbA1c
<6%. There were no demonstrated effects upon MH simply from improved glycemic control in the intensive arm. Although there is some evidence in the literature of modest benefits to emotional wellbeing from improved glycemia, studies are mixed plausibly because of treatment variation and approach (22
). In ACCORD both treatment arms had targets of improved glycemic control, with the intensive arm designed to achieve greater control albeit with potentially greater treatment complexity. Although the SF-36 PH component score was significantly different between groups, the absolute net difference of 0.5 units of change is trivial and well below a general threshold of ~3–5 points for a minimally important difference on these measures (19
) and therefore clinically insignificant. The pattern of results indicates that for all HRQL study outcome measures considered, with the exception of treatment satisfaction (which had a trend toward increased satisfaction), there was a pattern of stability over time in scores for both treatment groups. The SF-36 PH and MH component scores were preplanned HRQL outcome measures in this study. A post hoc analysis of the eight individual SF-36 scale score means exploring the consistency of effects among the HRQL concepts that comprise the SF-36 component scores revealed no unusual or inconsistent influences on these summary component scores.
The finding of no decrement in treatment satisfaction, either when compared with those in standard treatment arm or over time, is notable because one source of reluctance in initiating intensive treatment regimens like the ACCORD intervention is reasonable concern over patient burden. The lack of decrement in subjective wellbeing particularly in the context of intensive glucose treatment may be related to several processes. There was increased access to providers, including both clinic visits and telephone contact in the intensive treatment arm. This may have increased perceived care quality and may have supported patient self-efficacy for managing diabetes. Patients’ perception of optimal HbA1c
control in the intensive control arm, which sought to lower HbA1c
to < 6%, may also have been important in this regard. Research on treatment satisfaction in diabetes has shown that having improved blood glucose or HbA1c
levels is an important driver of satisfaction regardless of treatment intensity (23
) and may influence patient appraisals of treatment effectiveness. Thus the results from this study add to the literature on treatment intensity, finding that patients may perceive intensive treatment as favorable. The finding that patients perceived hyperglycemia as a bigger problem than hypoglycemia may indicate the relative importance patients attach to hyperglycemia versus hypoglycemia.
The early stopping of the ACCORD intensive glycemic control arm resulted in the transition of the intensively treated participants to standard glycemic control. Analysis examining HRQL outcomes of data up to glycemia trial discontinuation on 5 February 2008 and all data through to final follow-up showed that results were highly similar pre- and post-transition. Death and trial inactivity were censoring events in this repeated-measures analysis by dictating the last valid HRQL assessment point entered into analysis (last observation carried forward). In the HRQL study sample there were a total of 78 deaths over the study period; 25 of these events resulted in no valuable HRQL information (all time points missing); in 44 events, HRQL baseline and 12-month information was possible to collect, and in nine events all but the 48-month HRQL assessment was possible to collect. We examined baseline status predictors of death or inactivity in the HRQL sample from standard demographic status, lifestyle, comorbidity, diabetes, and biomarker variables. Results found higher frequency of either death or inactivity (events) was associated with older age, being a current smoker, living alone, albuminuria, and diastolic blood pressure. In a secondary analysis (data not shown) that included predictors of events produced highly similar results to the formal analysis presented above.
There are several potential limitations to consider when interpreting these data or findings. Our sample is not representative of the entire population of patients with type 2 diabetes. ACCORD participants had a mean age of 62, diabetes duration of 10 years, risk factors for CVD, a baseline HbA1c
≥7.5%, and willingness to undergo intensive treatment to control glucose, including frequent clinic visits and the use of insulin. Although we assessed a broad range of factors for their associations with HRQL, there are many other factors that could have been examined, especially in behavioral and psychosocial domains that may have been more responsive to potential burdens or risks with intensive glycemic control strategies. For example, our study did not include covariates concerning emotional state, mood, locus of control, social support, or others (5
), limiting our ability to comment on the role of these influences. For the DTSQ measure, during ACCORD vanguard, which enrolled 1,184 patients, item 8 (recommend treatment to others) was not assessed in either treatment group. Given the high internal consistency reliability of the DTSQ (α >0.85) we believe that this item omission in a subset of patients would have little appreciable impact on the estimated treatment effect for this outcome. Finally, although we included known correlates of death and participant study inactivity in our models to limit their influence in treatment group comparisons, this step could not remove all potential sources of bias and neither would the alternative of imputing missing values. We studied subjective, self-reported health appraisal of participants. A health utility measurement model is an alternative approach that allows for the outcome of death to be incorporated in health scores. We neither planned nor examined a utility model with these data.
In summary, this study demonstrated no significant HRQL benefit or harm from the ACCORD intensive glycemic control strategies. Participants in the intensive treatment arm reported a greater increase in satisfaction with their diabetes treatment. The latter result suggests that new or emerging treatment strategies in diabetes that are both intensive and safe could be perceived by patients as worthwhile and that treatment acceptability is not a limiting factor in complex interventions such as ACCORD.