Sequential drug decision problems in long-term medical conditions: a case Study of Primary Hypertension Eunju Kim ba, ma, msc

2) Cluster analysis depending on the first, second, third and fourth-line drug

Cluster analyses were conducted for better understanding on the nature of the estimated total net benefits of the 4,128 policies. Firstly, all possible treatment sequences were divided into four groups depending on the initial drug and named Group 1 for the policies starting with Ds, Group 2 for the policies starting with BBs, Group 3 for the policies starting with CCBs and Group 4 for the policies starting with ACEIs/ARBs. If there was a significant difference between group means by the Analysis of Variance (ANOVA), a multiple comparison test using the Tukey’s Honestly significant difference criterion (Tukey’s HSD) was performed^[375].

ANOVA showed that there was no significant difference between the means of the four defined groups (see Figure ‎7.). The mean of Group 1 was £319,410, Group 2 was £ 319,180, Group 3 was £ 319,160 and Group 4 was £ 319,310 (p=0.51705).

1) X-axis represents the groups divided by initial drugs (1: Ds, 2: BBs, 3: CCBs and 4: ACEIs/ARBs).

Figure ‎7.. Graphical summary of the mean and CIs for each group classified by initial drug

All possible treatment sequences were also divided into 10 groups depending on the second-line drug, and named from Group 1 to Group 10 for the groups whose second-line drug was Ds, BBs, CCBs, ACEIs/ARBs, Ds+BBs, Ds+CCBs, Ds+ACEIs/ARBs, BBs+CCBs, BBs+ACEIs/ARBs and CCBs+ACEIs/ARBs (see Figure ‎7.). ANOVA found that there was a significant difference in total net benefit between 10 groups defined by the second-line drug (p<0.05). The result from Tukey’s HSD analysis in Figure ‎7. shows the significant different in total net benefit between, where single drugs were used and where two-drug combination drugs were used as the second-line drug. The average total net benefit was highest where CCBs+ACEIs/ARBs was used as the second-line drug (£321,999) followed by where Ds+ACEIs/ARBs or Ds+CCBs were used as the second-line drug (£321,361 and £ 321,056). The rest groups had means significantly lower than those three groups.

Cluster analyses also found significant differences between 14 groups defined by the third or fourth-line drug (p<0.05 for both). In both cases, the group means were greater where three-drug combinations were used as the third or fourth-line drug followed by two-drug combinations and single drugs (see Figure ‎7. and Figure ‎7.). In the comparison between 14 groups divided by the third-line drug, the group of sequential treatment policies using Ds+CCBs+ACEIs/ARBs as the third-line drug had the significantly greater mean than the other 13 policies (£325,797). In contrast, no significant difference was found between the policies using three-drug combinations as the fourth-line treatment.

		1) Group 1 to Group 10 represent the set of treatment sequences whose second-line drug is Ds, BBs, CCBs, ACEIs/ARBs, Ds+BBs, Ds+CCBs, Ds+ACEIs/ARBs, BBs+CCBs, BBs+ACEIs/ARBs and CCBs+ACEIs/ARBs, respectively. 2) Cycle represents the mean of total net benefits; horizontal line represents the comparison intervals; the blue colour represents the group, which has the highest average total net benefit; the grey colour represents the group whose average total net benefit is not significantly different with the group, which has the highest average total net benefit; and the red colour represents the group whose average total net benefit is significantly different with the group, which has the highest average total net benefit. Figure ‎7.. Graphical summary of the mean and comparison intervals for each group classified by second-line drug
	1) Group 1 to Group 14 represent the set of treatment sequences whose third-line drug is Ds, BBs, CCBs, ACEIs/ARBs, Ds+BBs, Ds+CCBs, Ds+ACEIs/ARBs, BBs+CCBs, BBs+ACEIs/ARBs, CCBs+ACEIs/ARBs, Ds+BBs+CCBs, Ds+BBs+ACEIs/ARBs, Ds+CCBs+ACEIs/ARBs and BBs+CCBs+ACEIs/ARBs, respectively. 2) Cycle represents the mean of total net benefits; horizontal line represents the comparison intervals; the blue colour represents the group, which has the highest average total net benefit; the grey colour represents the group whose average total net benefit is not significantly different with the group, which has the highest average total net benefit; and the red colour represents the group whose average total net benefit is significantly different with the group, which has the highest average total net benefit. Figure ‎7.. Graphical summary of the mean and comparison intervals for each group classified by third-line drug
	1) Group 1 to Group 14 represent the set of treatment sequences whose third-line drug is Ds, BBs, CCBs, ACEIs/ARBs, Ds+BBs, Ds+CCBs, Ds+ACEIs/ARBs, BBs+CCBs, BBs+ACEIs/ARBs, CCBs+ACEIs/ARBs, Ds+BBs+CCBs, Ds+BBs+ACEIs/ARBs, Ds+CCBs+ACEIs/ARBs and BBs+CCBs+ACEIs/ARBs, respectively. 2) Cycle represents the mean of total net benefits; horizontal line represents the comparison intervals; the blue colour represents the group, which has the highest average total net benefit; the grey colour represents the group whose average total net benefit is not significantly different with the group, which has the highest average total net benefit; and the red colour represents the group whose average total net benefit is significantly different with the group, which has the highest average total net benefit. Figure ‎7.. Graphical summary of the mean and comparison intervals for each group classified by fourth-line drug