Resource utilization and healthcare costs for acute coronary syndrome patients with and without diabetes mellitus

Abstract

Objective:

This study compared differences in healthcare costs and resource utilization for acute coronary syndrome (ACS) patients with and without diabetes mellitus (DM).

Methods:

A retrospective cohort study of a large, US employer-based claims database identified adults hospitalized for ACS between 01/01/2005 and 12/31/2006 and categorized them based on DM status. Resource utilization and costs during the index hospitalization and in the 12-month follow-up period were compared for ACS patients with and without DM using the propensity score stratification bootstrapping method, adjusting for differences in demographic and clinical characteristics.

Results:

Of 12,502 patients who met selection criteria, 3,040 (24%) had a history of DM and 9,462 (76%) did not. Patients with DM were older, female, and had higher rates of previous cardiovascular and renal diseases. After the propensity score stratification, patients with DM incurred higher index hospitalization costs ($32,577 vs. $29,150, p?<?0.01) as well as higher total follow-up healthcare costs ($35,400 vs. $24,080, p?<?0.01), including higher inpatient ($17,278 vs. $11,247, p?<?0.01), outpatient ($12,357 vs. $8,853, p?<?0.01), and pharmacy costs ($5,765 vs. $3,980, p?<?0.01).

Limitations:

General limitations exist with any retrospective claims database analysis including potential diagnostic or procedural coding inaccuracies. Additionally, the patient population was representative of a working-age population with employer-sponsored health insurance and results may not be generalizable to other patient populations.

Conclusions:

DM is significantly associated with increased healthcare resource utilization and costs for ACS patients.     

Humanistic and economic impacts of hepatitis C infection in the United States

Abstract

Objective:

Prior research examining the effect of hepatitis C virus (HCV) on health-related quality of life (HRQoL) and healthcare costs is flawed because non-patient controls were not adequately comparable to HCV patients. The current study uses a propensity score matching methodology to address the following research question: is the presence of diagnosed hepatitis C (HCV) associated with poorer health-related quality of life (HRQoL) and greater healthcare resource use?

Methods:

Using data from the 2009 US National Health and Wellness Survey, patients who reported a HCV diagnosis (n?=?695) were compared to propensity-matched controls (n?=?695) on measures of HRQoL and healthcare resource use. All analyses applied sampling weights to project to the US population.

Results:

HCV patients reported significantly lower levels of HRQoL relative to the matched-control group, including the physical component score (39.6 vs. 42.7, p?<?0.0001) and health utilities (0.63 vs. 0.66, p?<?0.0001). The number of emergency room visits (0.59 vs. 0.44, p?<?0.05) and physician visits (7.7 vs. 5.9, p?<?0.05) in the past 6 months were significantly higher for the HCV group relative to matched controls.

Conclusion:

The results of this study suggest that HCV represents a substantial burden on patients by having a significant and clinically-relevant impact on key dimensions of HRQoL as well as on utilization of healthcare resources, the latter of which would result in increased direct medical costs.

Limitations:

Due to limitations of the internet survey approach (e.g., inability to confirm HCV diagnosis), future research is needed to confirm these findings.     

Comparison of medical costs and healthcare resource utilization of post-menopausal women with HR+/HER2− metastatic breast cancer receiving everolimus-based therapy or chemotherapy: a retrospective claims database analysis

Objective:

To analyze medical costs and healthcare resource utilization (HRU) associated with everolimus-based therapy or chemotherapy among post-menopausal women with hormone-receptor-positive, human-epidermal-growth-factor-receptor-2-negative (HR+/HER2?) metastatic breast cancer (mBC).

Methods:

Patients with HR+/HER2? mBC who discontinued a non-steroidal aromatase inhibitor and began a new line of treatment with everolimus-based therapy or chemotherapy (index therapy/index date) between July 20, 2012 and April 30, 2014 were identified from two large claims databases. All-cause, BC-related, and adverse event (AE)-related medical costs (in 2014 USD) and all-cause HRU per patient per month (PPPM) were analyzed for both treatment groups across patients’ first four lines of therapies for mBC. Adjusted differences in costs and HRU between the everolimus and chemotherapy treatment group were estimated pooling all lines and using multivariable generalized linear models, accounting for difference in patient characteristics.

Results:

A total of 3298 patients were included: 902 everolimus-treated patients and 2636 chemotherapy-treated patients. Compared to chemotherapy, everolimus was associated with significantly lower all-cause (adjusted mean difference?=?$3455, p?<?0.01) and BC-related ($2510, p?<?0.01) total medical costs, with inpatient ($1344, p?<?0.01) and outpatient costs ($1048, p?<?0.01) as the main drivers for cost differences. Everolimus was also associated with significantly lower AE-related medical costs ($1730, p?<?0.01), as well as significantly lower HRU (emergency room incidence rate ratio [IRR]?=?0.83; inpatient IRR?=?0.74; inpatient days IRR?=?0.65; outpatient IRR?=?0.71; BC-related outpatient IRR?=?0.57; all p?<?0.01).

Conclusions:

This retrospective claims database analysis of commercially-insured patients with HR+/HER2? mBC in the US showed that everolimus was associated with substantial all-cause, BC-related, and AE-related medical cost savings and less utilization of healthcare resources relative to chemotherapy.     

Characterizing the financial burden of pulmonary arterial hypertension within an integrated healthcare delivery system

Abstract

Purpose:

Financial burden associated with providing healthcare to patients with pulmonary arterial hypertension (PAH) is poorly characterized. This study sought to quantify 3-year healthcare expenditures and determine whether expenditures differed between incident and prevalent PAH cases.

Methods:

This was a retrospective cohort study of Kaiser Permanente Colorado (KPCO) patients with confirmed diagnosis of PAH. Included patients were followed from study entry until 3 years, death, or termination of KPCO membership, whichever came first. All expenditures were reported in 2011 US dollars from the KPCO perspective.

Results:

In total, 157 patients were included: 44 (28%) prevalent and 113 (72%) incident cases. Mean age (prevalent vs incident cases) was 61 years vs 67 years and 13.6% vs 27.4% were males. The majority of patients (55%) were classified as WHO Group 1 PAH. Prevalent cases had less follow-up (843 vs 975 days; p?=?0.033). Overall, median total per patient per day (PPPD) and 3-year total expenditures were $56 (interquartile range (IQR?=?$29–$166) and $50,599 (IQR?=?$25,958–$135,535), respectively. After adjustment for patient characteristics and chronic disease burden, median PPPD ($54 vs $56; p?=?0.950) and 3-year ($37,340 vs $55,073; p?=?0.111) total expenditures were equivalent between prevalent and incident cases; however, the risk of death during the 3-year follow-up was lower among incident cases (hazard ratio?=?0.41, 95% CI?=?0.18–0.91). No significant differences were detected in pharmacy, inpatient, medical office, emergency department, or other expenditures. Median PAH specialty medication PPPD expenditures were also equivalent, also ($226 vs $223 among specialty medication users; p?=?0.861).

Conclusion:

Healthcare expenditures related to PAH represent substantial financial burden. Significant differences according to prevalent or incident case status appeared to be driven by median ED and inpatient expenditures; however, PAH specialty medication expenditures represented a substantial cost-driver overall. Future efforts should focus on optimizing care for patients with PAH to avoid unnecessary harm or waste.     

Clinical comorbidities,treatment patterns,and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care

Abstract

Objective:

To assess comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or duloxetine (index event) in usual care settings.

Methods:

Using the LifeLink? Health Plan Claims Database, patients with FM (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) were identified. Patients initiated on duloxetine were propensity score-matched with patients initiated on pregabalin (n?=?826; mean age [standard deviation] of 48.3 [9.3] years for both groups). Prevalence of comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods.

Results:

Both patient groups had multiple comorbidities and a substantial pain-related and adjuvant medication burden. In the pregabalin group, use of other anticonvulsants decreased significantly (31.6% vs 24.9%), whereas use of serotonin-norepinephrine reuptake inhibitors (SNRIs; 16.5% vs 22.5%) and topical agents (10.1% vs 13.2%) increased in the follow-up period (p?<?0.01). In the duloxetine group, there were significant decreases in the use of other SNRIs (13.0% vs 5.7%), selective serotonin reuptake inhibitors (41.3% vs 21.7%), and tricyclic antidepressants (18.8% vs 13.2%), and an increase in the use of anticonvulsants (28.6% vs 40.1%; p?<?0.0001). There were significant increases (p?<?0.0001) in pharmacy and total healthcare costs in both cohorts, and a significant increase in outpatient costs (p?=?0.0084) in the duloxetine cohort from pre-index to follow-up. There were no significant differences in median total healthcare costs between the pregabalin and duloxetine groups in both the pre-index ($10,159 vs $9,556) and follow-up ($11,390 vs $11,746) periods.

Limitations:

Limitations of this study are typical of those associated with retrospective database analyses.

Conclusions:

Patients with FM prescribed pregabalin or duloxetine were characterized by a significant comorbidity and pain/adjuvant medication burden. Although healthcare costs increased in both groups, there were no statistically significant differences in direct healthcare costs between the two groups.     

Economic impact of using inhaled corticosteroids without prior exacerbation among elderly patients with chronic obstructive pulmonary disorder

Abstract

Objective:

To assess the economic impact of initiating inhaled corticosteroids (ICS) without evidence of prior exacerbation among elderly patients with chronic obstructive pulmonary disease (COPD) in the US.

Methods:

This retrospective study used administrative claims to identify newly diagnosed COPD patients between 1/1/2005 and 6/30/2006 who were dispensed ICS. The dispense date of the first ICS was set as the index date. Patients with prior diagnoses for asthma, cystic fibrosis, or lung cancer were excluded. Cohorts were constructed based on whether ICS therapy was concordant with recommended guidelines of having prior COPD exacerbation. Each COPD patient with prior exacerbation was matched to four patients without exacerbation based on age, gender, Charlson Comorbidity Index, and whether COPD diagnosis code was not elsewhere specified (i.e., 496). Multivariate regressions were estimated to assess the association between use of ICS therapy without prior exacerbation and total healthcare costs, controlling for demographics and clinical characteristics.

Results:

The study included 3650 patients: 730 with prior exacerbation and 2920 without prior exacerbation. Patients were 76 years of age and 54% were male. Those with prior exacerbation were more likely to have inpatient stays both prior to (74.4 vs. 44.1%, p?<?0.05) and following (37.0 vs. 33.1%, p?<?0.05) the index date. Controlling for patient characteristics, patients who were dispensed ICS without prior exacerbation had $1859 higher in total costs (p?<?0.05) compared to patients with prior exacerbation during the 12 months following ICS initiation.

Limitations:

The retrospective design of this study limits the interpretation of findings as association and not causality. This study is subject to selection bias due to unobservable confounders.

Conclusions:

Among COPD patients, initiation of ICS without prior exacerbation appears to be associated with increased healthcare costs. These findings suggest that ICS initiation without evidence of exacerbation as consistent with guidelines is associated with adverse economic consequences.     

Clinical characteristics,pharmacotherapy, and healthcare resource use among patients with fibromyalgia newly prescribed pregabalin or tricyclic antidepressants

Abstract

Objective:

To examine treatment patterns and costs among patients with fibromyalgia prescribed pregabalin or tricyclic antidepressants (TCAs).

Methods:

Using the LifeLink? Health Plan Claims Database, patients with fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) newly prescribed (index date) TCAs (n?=?898) were identified and propensity score-matched (PSM) with patients newly prescribed pregabalin (n?=?898). Pain-related pharmacotherapy, comorbidities, and healthcare resource use/costs were examined during the 12 months, pre-index, and follow-up periods.

Results:

Both patient groups reported multiple comorbidities and received pain medications in the pre-index and follow-up periods. Among patients prescribed pregabalin, use of non-selective non-steroidal anti-inflammatory drugs (43.3% vs 39.8%), other anticonvulsants (28.6% vs 23.3%), and tetracyclic/miscellaneous antidepressants (28.5% vs 25.8%) significantly decreased, and cyclooxygenase 2 (COX-2) inhibitors (7.7% vs 10.4%), TCAs (4.8% vs 7.9%), and topical agents (10.8% vs 15.1%) increased in the follow-up period (p?<?0.05). Among patients prescribed TCAs, there were significant decreases in muscle relaxants (42.0% vs 38.4%) and sedative hypnotics (27.4% vs 23.9%), and increases in COX-2 inhibitors (5.8% vs 7.9%) and anticonvulsants (25.1% vs 33.7%; p?<?0.05). There were increases (p?<?0.0001) in pharmacy costs in both cohorts and total healthcare costs in the pregabalin cohort from pre-index to follow-up. Median total costs were higher (p?<?0.05) in the pregabalin group vs TCAs in the pre-index ($9935 vs $8771) and follow-up ($10,689 vs $8379) periods.

Limitations:

Despite attempts to address bias through PSM, the higher pre-index costs in the pregabalin cohort suggest a channeling of patients with more severe fibromyalgia to pregabalin.

Conclusions:

Patients with fibromyalgia prescribed pregabalin or TCAs had multiple comorbidities and a sizeable pain medication burden, which increased in the follow-up period for both cohorts. Only 5% of pregabalin initiators had been treated with concomitant TCAs at baseline, suggesting that TCAs were inappropriate for these patients owing to their contraindications.     

Impact of completing chronic hepatitis C (CHC) treatment on post-therapy healthcare cost

Background:

Chronic hepatitis C (CHC) is associated with significant economic burden. This study evaluated the healthcare cost alleviation associated with treatment of CHC.

Methods:

Health insurance claims from 60 self-insured US companies were analyzed (01/2001–03/2012). Adult patients with ≥1 CHC diagnosis (ICD-9-CM: 070.44, 070.54), initiating interferon, and with ≥2 dispensings and with ≥48 weeks of follow-up were selected. Patients diagnosed with HIV or who completed only 24 weeks of interferon therapy (a surrogate for CHC genotypes 2 and 3) were excluded from the study. Interferon users were categorized into complete and discontinued therapy cohorts. During the post–48-week treatment period, cohorts were compared for healthcare resource utilization using rate ratios (RRs), as well as healthcare costs using per-patient per-year (PPPY) cost differences.

Results:

A total of 1017 patients who completed and 953 patients who discontinued interferon therapy were identified. Relative to the discontinued therapy cohort, the completed therapy cohort had significantly fewer hospitalizations (RR [95% CI]?=?0.74 [0.68, 0.81], p?p?p?=?0.039), which translated into significantly lower total healthcare costs PPPY (cost difference [95% CI]?=?$4540 [1570, 7680], p?=?0.004) and hospitalization costs (cost difference [95% CI]?=?$3039 [1140, 5248], p?=?0.002). Non–CHC-related costs accounted for 55% and CHC-related costs for 45% of the all-cause cost difference between cohorts.

Limitations:

Claims data may have contained inaccuracies, and genotypes of patients with CHC could not be confirmed. The study consisted of privately insured individuals and may not be generalizable to the entire CHC population.

Conclusion:

Compared to discontinued therapy patients, CHC patients who completed interferon therapy and presumably had a higher rate of achieving SVR were found to have lower levels of healthcare resource utilization and costs post-therapy. The reduction was primarily in costs associated with non–HCV-related comorbidities.     

Economic simulation of canagliflozin and sitagliptin treatment outcomes in patients with type 2 diabetes mellitus with inadequate glycemic control

Abstract

Objectives:

This study examines the association between changes in diabetes-related quality measures (QMs) (HbA1c, systolic and diastolic blood pressure [BP], low-density lipoprotein cholesterol [LDL-C], and body weight) and healthcare costs in Type 2 diabetes mellitus (T2DM) patients. It also performs an economic simulation that evaluates the cost implications of the changes in QMs and of the incidence rates (IRs) of adverse events (AEs) associated with canagliflozin (CANA) and sitagliptin (SITA) treatments in a real-world setting.

Methods:

Health-insurance claims and electronic medical records from the Reliant Medical Group database (2007–2011) were used to identify adult patients with T2DM receiving metformin and sulfonylurea who did not achieve adequate glycemic control. The association between the changes in QMs and healthcare costs was evaluated using multivariate regression and non-parametric bootstrap methods. AE-related costs were taken from the literature. The cost impact of CANA and SITA outcomes was evaluated using the aforementioned costs and the changes in QMs and the IRs of AEs observed in a recent phase 3 trial comparing CANA and SITA as third oral agent (DIA3015).

Results:

Eight hundred and fifty-six T2DM patients were identified (mean age?=?65.8; female 45.4%). The regression analysis found that increases of 1 percentage point in HbA1C and 1% in systolic and diastolic BP, LDL-C, or weight were associated with a per patient per year (PPPY) cost increase of $4476 (p?=?0.028) and $566 (p?=?0.006), a decrease of $362 (p?=?0.070) and $7 (p?=?0.817), and an increase of $241 (p?=?0.481), respectively. The economic simulation showed that changes in QMs and IRs of AEs equivalent to those reported in DIA3015 would be associated with a reduction in PPPY healthcare costs of $6061 (p?=?0.036) for CANA and $2190 (p?=?0.098) for SITA.

Conclusions:

This study suggests that integrated approaches that manage to control a combination of quality measures are most successful at reducing downstream healthcare costs.     

Indirect costs associated with metastatic breast cancer

Abstract

Objective:

To compare the indirect costs of productivity loss between metastatic breast cancer (MBC) and early stage breast cancer (EBC) patients, as well as their respective family members.

Methods:

The MarketScan® Health and Productivity Management database (2005–2009) was used. Adult BC patients eligible for employee benefits of sick leave and/or short-term disability were identified with ICD-9 codes. Difference in sick leave and short-term disability days was calculated between MBC patients and their propensity score matched EBC cohort and general population (controls) during a 12-month follow-up period. Generalized linear models were used to examine the impact of MBC on indirect costs to patients and their families.

Results:

A total of 139 MBC, 432 EBC, and 820 controls were eligible for sick leave and 432 MBC, 1552 EBC, and 4682 controls were eligible for short-term disability (not mutually exclusive). After matching, no statistical difference was found in sick leave days and the associated costs between MBC and EBC cohorts. However, MBC patients had significantly higher short-term disability costs than EBC patients and controls (MBC: $6166?±?$9194 vs EBC: $3690?±?$6673 vs Controls: $558?±?$2487, both p?<?0.001). MBC patients had more sick leave cost than controls ($2383?±?$5539 vs $1282?±?$2083, p?<?0.05). Controlling for covariates, MBC patients incurred 47% more short-term disability costs vs EBC patients (p?=?0.009). Older patients (p?=?0.002), non-HMO payers (p?<?0.05), or patients not receiving chemotherapy during follow-up (p?<?0.001) were associated with lower short-term disability costs. MBC patients’ families incurred 39.7% (p?=?0.06) higher indirect costs compared to EBC patients’ families after controlling for key covariates.

Conclusion:

Productivity loss and associated costs in MBC patients are substantially higher than EBC patients or the general population. These findings underscore the economic burden of MBC from a US societal perspective. Various treatment regimens should be evaluated to identify opportunities to reduce the disease burden from the societal perspective.     

Adherence to iron chelation therapy and associated healthcare resource utilization and costs in Medicaid patients with sickle cell disease and thalassemia

Background:

Sub-optimal patient adherence to iron chelation therapy (ICT) may impact patient outcomes and increase cost of care. This study evaluated the economic burden of ICT non-adherence in patients with sickle cell disease (SCD) or thalassemia.

Methods:

Patients with SCD or thalassemia were identified from six state Medicaid programs (1997–2013). Adherence was estimated using the medication possession ratio (MPR) of ≥0.80. All-cause and disease-specific resource utilization per-patient-per-month (PPPM) was assessed and compared between adherent and non-adherent patients using adjusted incidence rate ratios (aIRR). All-cause and disease-specific healthcare costs were computed using mean cost PPPM. Regression models adjusting for baseline characteristics were used to compare adherent and non-adherent patients.

Results:

A total of 728 eligible patients treated with ICT in the SCD cohort, 461 (63%) adherent, and 218 in the thalassemia cohort, 137 (63%) adherent, were included in this study. In SCD patients, the adjusted rate of all-cause outpatient visits PPPM was higher in adherent patients vs non-adherent patients (aIRR [95% CI]: 1.05 [1.01–1.08], p?<?0.0001). Conversely, adherent patients incurred fewer all-cause inpatients visits (0.87 [0.81–0.94], p?<?0.001) and ER visits (0.86 [0.78–0.93], p?<?0.001). Similar trends were observed in SCD-related resource utilization rates and in thalassemia patients. Total all-cause costs were similar between adherent and non-adherent patients, but inpatient costs (adjusted cost difference?=??$1530 PPPM, p?=?0.0360) were lower in adherent patients.

Conclusion:

Patients adherent to ICT had less acute care need and lower inpatient costs than non-adherent patients, although they had more outpatient visits. Improved adherence may be linked to better disease monitoring and has the potential to avoid important downstream costs associated with acute care visits and reduce the financial burden on health programs and managed care plans treating SCD and thalassemia patients.     

Switching of biologic disease modifying anti-rheumatic drugs in patients with rheumatoid arthritis in a real world setting

Objectives:

This study examined total healthcare costs and rates of patients with rheumatoid arthritis (RA) who switch biologic disease-modifying anti-rheumatic drug (bDMARD) therapy in a real world setting.

Methods:

A retrospective longitudinal analysis was conducted in patients with RA using IMS PharMetrics Plus database from 1/1/2004 to 3/31/2010. The first-line cohort included patients newly initiated on abatacept or the tumor necrosis factor-alpha inhibitors (anti-TNFs) adalimumab, etanercept, or infliximab, with 12 months of continuous follow-up. The second-line cohort included patients initiating a bDMARD with evidence of a different bDMARD within the previous 2 years and with 12 months of continuous follow-up. Switching was defined as a different bDMARD claim within a 200% gap in days supply from the previous bDMARD claim. Non-switchers stayed on their bDMARD in the follow-up period. Monthly total healthcare costs for switchers and non-switchers and rates of bDMARD switching were examined. Switch rates for each bDMARD were also compared.

Results:

First-line switchers had significantly higher monthly total healthcare costs after the switch than non-switchers ($3759 vs $2343; p?p?Limitations:

There are no clinical data available in this database and, therefore, this study did not examine the clinical drivers of healthcare costs and switch rates.

Conclusions:

Monthly total healthcare costs were higher for bDMARD switchers following the switch compared to non-switchers. Patients on abatacept switched less frequently than patients on anti-TNFs. This study highlights the need to identify patients who are likely to switch in order to ensure they receive the appropriate therapy which may improve outcomes and decrease healthcare costs.     

Economic outcomes of exenatide vs liraglutide in type 2 diabetes patients in the United States: results from a retrospective claims database analysis

Abstract

Objective:

The safety and efficacy of the GLP-1 receptor agonists exenatide BID (exenatide) and liraglutide for treating type 2 diabetes mellitus (T2DM) have been established in clinical trials. Effective treatments may lower overall treatment costs. This study examined cost offsets and medication adherence for exenatide vs liraglutide in a large, managed care population in the US.

Methods:

This was a retrospective cohort analysis comprising adult patients with T2DM who initiated exenatide or liraglutide between 1/1/2010 and 6/30/2010 and had 6 months pre-index and post-index continuous eligibility. Patients were propensity score-matched to controls for baseline differences. Medication adherence was measured by proportion of days covered (PDC). Paired t-test and McNemar’s test were used to compare outcomes.

Results:

Matched exenatide and liraglutide cohorts (n?=?1347 pairs) had similar average total 6-month follow-up costs ($6688 vs $7346). However, exenatide patients had significantly lower mean pharmacy costs ($2925 vs $3272, p?<?0.001). Among liraglutide patients, patients receiving the 1.8?mg dose had significantly higher average total costs compared to those receiving the 1.2?mg dose ($8031 vs $6536, p?=?0.026), with higher mean pharmacy costs in the 1.8?mg cohort ($3935 vs $3146, p?<?0.001). There were no significant differences in inpatient or outpatient costs or medication adherence between groups (mean PDC: exenatide 56% vs liraglutide 57%, p?=?0.088).

Limitations:

The study assumed that all information needed for case classification and matching of cohorts was present and not differential across cohorts. The study did not control for covariates that were unavailable, such as HbA1c and duration of diabetes.

Conclusions:

Patients initiating exenatide vs liraglutide for T2DM had similar medication adherence and total healthcare costs; however, exenatide patients had significantly lower total pharmacy costs. Patients prescribed 1.8?mg liraglutide had significantly higher costs compared to those on 1.2?mg.