Abstract

Zartashia Ghani, Sanjib Saha, Johan Jarl, Martin Andersson, Johan Sanmartin Berglund, Peter Anderberg
[Journal of Alzheimer’s Disease, 86(4) (2022) 1629–1641, DOI 10.3233/JAD-215013]
http://doi.org/10.3233/JAD-215013
“For PwMCI, the mean difference in total costs between intervention and standard care was € 12 (95% CI: –2090 to 2115) (US$ = € 1.19) and the mean QALY change was –0.004 (95% CI: –0.009 to 0.002). For informal caregivers, the cost difference was –€ 539 (95% CI: –2624 to 1545) and 0.003 (95% CI: –0.002 to 0.008) for QALY. The difference in cost and QALY for PwMCI and informal caregivers combined was –€ 527 (95% CI: –3621 to 2568) and –0.001 (95% CI: –0.008 to 0.006). Although generally insignificant differences, this indi- cates that SMART4MD, compared to standard care was: 1) more costly and less effective for PwMCI, 2) less costly and more effective for informal caregivers, and 3) less costly and less effective for PwMCI and informal caregivers combined.”
“For PwMCI, the mean difference in total costs between intervention and standard care was €396 (95% CI: –444 to 1236) (1 €= US$1.19) and the mean QALY change was –0.004 (95% CI: –0.009 to 0.002). For informal caregivers, the cost difference was €178 (95% CI: –715 to 1071) and 0.003 (95% CI: –0.002 to 0.008) for QALY. The difference in cost and QALY for PwMCI and informal caregivers combined was €574 (95% CI: –641 to 1789) and –0.001 (95% CI: –0.008 to 0.006). Although generally insignificant differences, this indicates that SMART4MD, compared to standard care was: 1) more costly and less effective for PwMCI, 2) more costly and more effective for informal caregivers, and 3) more costly and less effective for PwMCI and informal caregivers combined.”
This should instead be removed and not considered as part of the eligibility criteria in the trial, since participants in the intervention group were provided with data-enabled tablets. This correction pertains to the description of our analytic sample and does not affect the results of the study or their interpretation.
“The top 5% (cost≥€ 25,741) were removed from the analysis to exclude the high-cost outliers.”
“The top 5% (cost≥€ 7,995 for PwMCI; cost≥€ 8,559 for informal caregivers; and cost≥€ 13,516 for PwMCI and informal caregivers combined) were removed from the analysis to exclude the high-cost outliers.”
“The total 6-month cost per PwMCI in the intervention and control group was on average €8,188 and €8,175 per person, respectively (Table 2). The greatest share of healthcare costs in both groups was related to outpatient care (75%). For informal caregivers, the total 6-month cost for intervention and control groups were on average €6,050 and €6,589, respectively (Table 2). Informal caregivers in the intervention group had higher outpatient and lower inpatient costs compared to the control group. The total 6-month cost for the dyads was lower for the intervention group (€14,238) compared to the control group (€14,764). None of the cost differences between the groups was statistically significant.”
Number of healthcare visits and related cost (€) for the participants (mean and standard error)
Note: Independent sample t-test is used to assess the statistical differences between intervention and control group (inter-group [between groups] analysis). No statistically significant differences were found.
“The total 6-month cost per PwMCI in the intervention and control group was on average €2,491 and €2,096 per person, respectively (Corrected Table 2). The greatest share of healthcare costs in both groups was related to outpatient care (77% in the intervention group and 78% in the control group). For informal caregivers, the total 6-month cost for intervention and control groups were on average €1,858 and €1,680, respectively (Corrected Table 2). The total 6-month cost for the dyads was higher for the intervention group (€4,349) compared to the control group (€3,776). None of the cost differences between the groups was statistically significant.”
Number of healthcare visits and related cost (€) for the participants (mean and standard error)
Note: Independent sample t-test is used to assess the statistical differences between intervention and control group (inter-group [between groups] analysis). No statistically significant differences were found.
“For PwMCI, the intervention was dominated by standard care as the intervention group had higher costs (€12) and lower QALY compared to the control group. This was also shown with the negative NMB (–€187) (Table 4 & Supplementary Table 5). The CE plane showed that incremental CE-pairs were spread in all four quadrants with 47% in the northwest quadrant (more costly and less effective). Given a WTP of €48,876 per QALY, the CEAC indicated that the intervention had less than 50% probability of being cost-effective (Fig. 1). However, as there was a gain in QoL-AD and MMSE scores in the intervention group compared to the control group, the ICERs for these outcome measures were €36 and €57 per unit gain in QoL-AD and MMSE, respectively.
Differences in pooled mean cost and health effects with 95% CI, ICERs and NMB (€)
Abbreviations: ICER: incremental cost-effectiveness ratio; MMSE: mini-mental state examination; NMB: net monetary benefit; PwMCI: person with mild cognitive impairment; QALY: quality-adjusted life years; QoL-AD: quality of life in Alzheimer disease; ZBI: Zarit Caregiver Burden Inventory. Note: Incremental effect with positive value represent improved outcomes. We reversed ZBI scores in order to obtain this. While dominance may be demonstrated, no significant differences in incremental costs and effects were found (Independent t-test). Adjustments were made on 6-month values of effectiveness measures by regressing them on baseline values. aNumber of participants available for cost estimation first, followed by number of participants available for health effects.
Sensitivity analyses from healthcare provider perspective in ICERs
Abbreviations: ICER: incremental cost-effectiveness ratio; MMSE: mini-mental state examination; PwMCI: person with mild cognitive impairment; QALY: quality-adjusted life years; ZBI: Zarit Caregiver Burden Inventory. aNumber of participants available for cost estimation first, followed by number of participants available for health effects. Note: Incremental effect with positive value represent improved outcomes. We reversed ZBI scores in order to obtain this. Significance levels: P < 0.05*, 0.01** and 0.001***.
Mean cost, health effect and differences by bootstrap (5000) for intervention and control group
Abbreviations: MMSE: mini-mental state exam; PwMCI: person with mild cognitive impairment; QoL-AD: quality of life in Alzheimer disease; ZBI: Zarit Caregiver Burden Inventory. Note: adjustments are made on baseline data of the estimates. No statistically significant differences were found.
For informal caregivers, the intervention dominated standard care, i.e., the intervention was less costly and more effective in terms of QALY, with a NMB of €676 (Table 4 & Supplementary Table 5). Sixty percent of the CE-pairs were in the southeast quadrant (less costly and more effective) followed by 26% in the northeast quadrant (more costly and more effective) in the CE-plane. The CEAC indicated that the intervention had 70% probability of being cost-effective at WTP of €48,876 per QALY for the caregivers (Fig. 1). Moreover, the intervention also dominated standard care in terms of ZBI.
Combining PwMCI and informal caregiver indicated that the intervention group had lower costs and lower QALY than the control group. This means that the intervention can be considered cost-effective if the society’s willingness-to-accept a QALY loss was lower than the estimated ICER of €634,940. Presenting these results in terms of the NMB (of €486) indicated that intervention was cost-effective at the WTP of €48,876 (Table 4 & Supplementary Table 5). Thirty-seven percent of the CE-pairs were in the southwest quadrant (less costly and less effective) in the CE-plane and the intervention had 60% probability of being cost-effective at €48,876 WTP.”
“For PwMCI, the intervention was dominated by standard care as the intervention group had higher costs (€396) and lower QALY compared to the control group. This was also shown with the negative NMB (–€571) (Corrected Table 4 & Corrected Supplementary Table 5). The CE plane showed that incremental CE-pairs were spread in all four quadrants with 74 % in the northwest quadrant (more costly and less effective). Given a WTP of €48,876 per QALY, the CEAC indicated that the intervention had less than 25% probability of being cost-effective (Corrected Fig. 1). However, as there was a gain in QoL-AD and MMSE scores in the intervention group compared to the control group, the ICERs for these outcome measures were €1,192 and €1,886 per unit gain in QoL-AD and MMSE, respectively.
Differences in pooled mean cost and health effects with 95% CI, ICERs and NMB (€)
Abbreviations: ICER: incremental cost-effectiveness ratio; MMSE: mini-mental state examination; NMB: net monetary benefit; PwMCI: person with mild cognitive impairment; QALY: quality-adjusted life years; QoL-AD: quality of life in Alzheimer disease; ZBI: Zarit Caregiver Burden Inventory. Note: Incremental effect with positive value represent improved outcomes. We reversed ZBI scores in order to obtain this. While dominance may be demonstrated, no significant differences in incremental costs and effects were found (Independent t-test). Adjustments were made on 6-month values of effectiveness measures by regressing them on baseline values. aNumber of participants available for cost estimation first, followed by number of participants available for health effects.
Sensitivity analyses from healthcare provider perspective in ICERs
Abbreviations: ICER: incremental cost-effectiveness ratio; MMSE: mini-mental state examination; PwMCI: person with mild cognitive impairment; QALY: quality-adjusted life years; ZBI: Zarit Caregiver Burden Inventory. aNumber of participants available for cost estimation first, followed by number of participants available for health effects. Note: Incremental effect with positive value represent improved outcomes. We reversed ZBI scores in order to obtain this. Significance levels: P < 0.05*, 0.01** and 0.001***.
Mean cost, health effect and differences by bootstrap (5000) for intervention and control group
Abbreviations: MMSE: mini-mental state exam; PwMCI: person with mild cognitive impairment; QoL-AD: quality of life in Alzheimer disease; ZBI: Zarit Caregiver Burden Inventory. Note: adjustments are made on baseline data of the estimates. No statistically significant differences were found.
For informal caregivers, the intervention was more costly and more effective with an ICER of €63,571/QALY and a negative NMB of –€41 (Corrected Table 4 & Corrected Supplementary Table 5). Fifty-five percent of the CE-pairs were in the northeast quadrant (more costly and more effective) followed by 32% in the southeast quadrant (less costly and more effective) in the CE-plane. The CEAC indicated that the intervention had less than 50% probability of being cost-effective at WTP of €48,876 per QALY for the caregivers (Corrected Fig. 1). Moreover, the ICER for ZBI was €774 per unit reduction in caregiving burden.
Combining PwMCI and informal caregiver indicated that the intervention group had higher costs and lower QALY than the control group. This means that the intervention was dominated by standard care with a negative NMB of –€615 (Corrected Table 4 & Corrected Supplementary Table 5). Forty-nine percent of the CE-pairs were in the northwest quadrant (more costly and less effective) in the CE-plane and the intervention had less than 25% probability of being cost-effective at €48,876 WTP.”
“The exceptions were the results stratified for men and above 70 years of age for PwMCI, where the intervention appeared to be less costly and less effective as compared to base case results (intervention dominated by standard care).”
“The exceptions were the results after removing high-cost outliers for PwMCI, where the intervention appeared to be less costly and less effective as compared to base case results, although still not cost-effective. For informal caregivers, intervention was dominant for caregivers having some burden (ZBI<48).”
“In contrast, the intervention dominated standard care for informal caregivers. This implies that the SMART4MD intervention was more beneficial to the caregivers than the PwMCI. This is further enhanced by the results using care burden (ZBI) as the outcome measure. When combining PwMCI and caregivers, the intervention reduced both the costs and QALY, indicating that resources could be saved at the expense of loss of quality of life in the range of the present WTP threshold. The CEAC curve showed that the intervention has <50%, 70%, and 60% probability of being cost-effective for the PwMCI, caregivers and dyads respectively at €48,876 WTP, indicating a likelihood to be considered good value for money for caregivers and dyads.”
“For informal caregivers, the intervention was not cost-effective at the threshold of €48,876 used in this study. However, the results using care burden (ZBI) as the outcome measure showed a reduction in caregiving burden at a higher cost. When combining PwMCI and caregivers, the intervention was dominated by standard care. The CEAC curve showed that the intervention has <25% probability of being cost-effective for the PwMCI and dyads and <50% probability of being cost-effective for caregivers at €48,876 WTP. This indicates that the intervention is not considered to be good value for money.”
“In contrast, considering other outcome measures besides QALY for PwMCI, the ICER were €36 per QoL-AD gain and €57 per MMSE score gain, respectively.”
“In contrast, considering other outcome measures besides QALY for PwMCI, the ICER were €1,192 per QoL-AD gain and €1,886 per MMSE score gain, respectively.”

CE-plane from healthcare provider perspective and CEAC indicates probability of the SMART4MD being cost-effective at different values (€) of willingness-to-pay per QALY gain.

CE-plane from healthcare provider perspective and CEAC indicates probability of the SMART4MD being cost-effective at different values (€) of willingness-to-pay per QALY gain.
The point estimate in the CE-plane for PwMCI remains in the northwest quadrant but has shifted upward within this quadrant, as incremental costs have increased from € 12 to € 396. As a result, the probability of the intervention being cost-effective has decreased from less than 50% to less than 20%, as indicated in the corresponding CEAC.
For informal caregivers, the point estimate in the CE-plane shifted from the southeast quadrant to the northeast quadrant. This occurred as incremental costs changed from being negative (€ –539) in the original to positive (€ 178) in the corrected version. Consequently, the probability of the intervention being cost-effective decreased from 70% to less than 50%, as shown in the corresponding CEAC.
Similarly, for dyads, the point estimate in the CE-plane shifted from the southwest quadrant to the northwest quadrant. This change was due to incremental costs switching from negative (€ –527) in the original version to positive (€ 574) in the corrected version. As a result, the probability of the intervention being cost-effective decreased from 60% to less than 25%, as indicated in the corresponding CEAC.
