Estimating health-state utility values for patients with recurrent ovarian cancer using Functional Assessment of Cancer Therapy – General mapping algorithms

Figures & data

Table 1 Utility algorithms identified from the systematic literature review and mapping database

Author, year	Questions or scores included in algorithm	Mapping Equation		Characteristics of surveyed population used to generate mapping algorithm	Algorithm performance statistics		Range of possible values from algorithm
					Observed in original survey data	Predicted using original survey data
Dobrez, 2007 (and reported in Hess, 2013)^Citation9,Citation19	PWB1:“I have a lack of energy” PWB2: “I have nausea” FWB1 : “I am able to work (include work at home)” FWB2: “I am able to enjoy life”	Utility (TTO) = 1		Female: 47.0% Age (years): 57.0 ECOG performance status (0/1/2/3/unknown): 29.1%/26.4%/32.5%/1 1%l1% Prevalent cancer types: 17.5% breast cancer, 13.2% prostate and 11.4% head and neck Total FACT-G scores: n.r.	Mean: 0.805 SD: 0.284 Median: n.r. Range:0 to 1	Mean: 0.832 SD: 0.121 Median: n.r Range: 0.456 to 1.0 R2:nr MAE: 0.19	0.456–1.00
		$\begin{array}{l}+PWB1\{\begin{array}{c}-0.2222,\\ -0.1137,\\ 0,\end{array}\\ +PWB2\{\begin{array}{c}-0.1537,\\ 0,\end{array}\\ +FWB1\{\begin{array}{c}-0.04311,\\ 0,\end{array}\\ +FWB2\{\begin{array}{c}-0.1254,\\ -0.0641,\\ -0.0345,\\ 0,\end{array}\end{array}$	if “very much” or “quite a bit” if “somewhat” or “a little bit” if “none at all” if “very much” or “quite a bit” otherwise if “not at all” or “a little bit” otherwise if “not at all” or “a little bit” if “somewhat” if “quite a bit” if “very much”
Cheung, 2009^Citation18	PWB total score EWB total score FWB total score	Utility (EQ–5D)		Female: 62.9% Age (years): 49.3 ECOG performance status (0/1/2/3/unknown): 32.8%/40.3%/23.5%/3.4%/n.r. Prevalent cancer types: 37.1% breast cancer, 18.6% head and neck, 10.9% colorectal Mean total FACT-G scores: 81.1	Mean: 0.803 SD:0.156 Median: 0.769 Range: 0.246 to 1.00	Mean: 0.811 SD:0.130 Median: 0.822 Range: 0.393 to 0.999 R2:0.417 MAE: 0.095	0.238–0.998
		= 0.238 + 0.014 × PWB total + 0.006 × EWB total + 0.008 × FWB total
Longworth, 2014 (OLS)^Citation7,Citation20	PWB1: “I have lack of energy” PWB2: “I have trouble meeting the need of family” PWB3: “I have pain” EWB1: “I feel sad” EWB2: “I am losing hope” FWB1: “I am able to work”	Utility (EQ–5D)=0.186		Female: 51.0% Age (years): 59.3 ECOG performance status (0/1/2/3/unknown): 23.4%/48.4%/23.5%/4.7%/n.r. Prevalent cancer types: 11 types of advanced cancer including ovarian cancer. Mean total FACT-G scores: 78	Mean: 0.721 SD: 0.223 Median: 0.735 Range: −0.135 to 1.00	Mean: 0.721 SD: 0.163 Median: 0.755 Range: 0.115 to 0.962 R2: 0.535 MAE: 0.111	0.016–0.956
		$+PWB1\{\begin{array}{c}0,\\ 0.045,\\ 0.036,\\ 0.071,\\ 0.118,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
		$+PWB2\{\begin{array}{c}0,\\ 0.028,\\ 0.049,\\ 0.088,\\ 0.098,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if” A little bit” if “not at all”
		$+PWB3\{\begin{array}{c}0,\\ 0.125,\\ 0.219,\\ 0.240,\\ 0.342,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
		$+EWB1\{\begin{array}{c}0,\\ 0.085,\\ 0.019,\\ 0.006,\\ 0.004,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
		$+EWB2\{\begin{array}{c}0,\\ -0.081,\\ -0.007,\\ 0.013,\\ 0.060,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
		$+FWB1\{\begin{array}{c}0.152,\\ 0.150,\\ 0.130,\\ 0.113,\\ 0,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
Longworth, 2014 (Tobit)^Citation17,Citation20	PWB1: “I have lack of energy” PWB2: “I have pain” FWB1: “I am able to work” FWB2: “I am able to enjoy life”	Utlity (EQ–5D) = 0.23 1				Mean: 0.723 SD: 0.161 Median: 0.738 Range: 0.135 to 0.957 R2: n.r. MAE: 0.181	0.133–1.00
		$+PWB1\{\begin{array}{c}0,\\ 0.055,\\ 0.053,\\ 0.113,\\ 0.200,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
		$+PWB2\{\begin{array}{c}0,\\ 0.164,\\ 0.255,\\ 0.293,\\ 0.431,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
		$+FWB1\{\begin{array}{c}0.151,\\ 0.149,\\ 0.110,\\ 0.097,\\ 0,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”
		$+FWB2\{\begin{array}{c}-0.057,\\ -0.010,\\ -0.012,\\ -0.098,\\ 0,\end{array}$	if “very much” if “quite a bit” if “Somewhat” if “A little bit” if “not at all”

Abbreviations: n.r., not reported; ECOG, Eastern Cooperative Oncology Group; SD, Standard Deviation; MAE, Mean Absolute Error; PWB, Physical well-being; FWB, Functional well-being; EWB, Emotional well-being.

Table 2 Rank for each algorithm by goodness-of-fit indicator

Measures	Cheung^Citation18	OLS^Citation17	Tobit^Citation17,*	Dobrez^Citation19,**
Mean	3	1	2	4
SD	1	2	3	4
Median	3	2	1	–
Range (CI)	1	2	3	4
R^2	2	1	–	–
MAE	1	2	3	4
Mean overall rank	1.83	1.67	2.40	4.00

Notes:

* Mean overall rank based on five metrics;

** mean overall rank based on four metrics.

Abbreviations: SD, standard deviation; CI, confidence interval; MAE, mean absolute error; OLS, ordinary least squares.

Figure 1 Distribution of utilities, total FACT-G scores, and total FACT-O scores across all observations in the study.

Abbreviations: EQ, EuroQol; TTO, time trade-off; FACT-G, Functional Assessment of Cancer Therapy – General; FACT-O, FACT – Ovarian; OLS, ordinary least squares.

Table 3 Summary statistics for utilities by algorithm and patient population (pooled treatment groups)

Time period	Algorithm	Mean	Standard error	Median	Interquartile range
Intention-to-treat group
Screening	OLS^Citation17	0.802	0.009	0.821	0.719–0.912
	Tobit^Citation17	0.799	0.009	0.815	0.704–0.914
	Cheung^Citation18	0.828	0.007	0.842	0.762–0.912
	Dobrez^Citation19	0.860	0.006	0.852	0.822–0.922
Scheduled visits*	OLS^Citation17	0.786	0.008	0.799	0.699–0.885
	Tobit^Citation18	0.786	0.008	0.787	0.696–0.885
	Cheung^Citation18	0.811	0.007	0.820	0.733–0.907
	Dobrez^Citation19	0.845	0.006	0.849	0.788–0.909
Unscheduled visits	OLS^Citation17	0.720	0.015	0.729	0.632–0.820
	Tobit^Citation17	0.751	0.013	0.736	0.676–0.858
	Cheung^Citation18	0.769	0.012	0.775	0.697–0.868
	Dobrez^Citation19	0.816	0.011	0.852	0.743–0.878
Breast cancer antigen mutation subgroup (including germ-line and tumor-positive)
Screening	OLS^Citation17	0.787	0.013	0.820	0.694–0.888
	Tobit^Citation17	0.784	0.013	0.813	0.677–0.875
	Cheung^Citation18	0.812	0.010	0.815	0.731–0.895
	Dobrez^Citation19	0.853	0.009	0.852	0.815–0.886
Scheduled visits*	OLS^Citation17	0.768	0.013	0.784	0.681–0.871
	Tobit^Citation17	0.774	0.011	0.774	0.694–0.874
	Cheung^Citation18	0.799	0.010	0.810	0.706–0.893
	Dobrez^Citation19	0.837	0.008	0.842	0.789–0.894
Unscheduled visits	OLS^Citation17	0.708	0.024	0.707	0.594–0.811
	Tobit^Citation17	0.737	0.020	0.72	0.676–0.806
	Cheung^Citation18	0.763	0.017	0.765	0.706–0.856
	Dobrez^Citation19	0.831	0.015	0.852	0.809–0.852

Note:

* Calculated as an average of the average utility score for each patient during the scheduled visits.

Abbreviation: OLS, ordinary least squares.

Table 4 Coefficients of mixed-effect regression model (OLS predicted utilities)

Outcome	Estimated coefficient	Standard error	P-value
Single-variable analysis
Time since randomization (continuous measure, days)	−0.00004	0.0001	0.2900
BRCA-mutation status
Positive	−0.0321	0.0162	0.0489
Wild-type or not tested (reference)	–	–	–
Randomization group
Placebo	−0.0138	0.0163	0.3973
Olaparib (reference)	–	–	–
AEs
Any grade 1 or 2	−0.0188	0.0103	0.0685
No grade 1 or 2 (reference)	–	–	–
AEs
Any grade 3 or above	−0.0204	0.0161	0.2065
No grade 3 or above (reference)	–	–	–
AEs (categorical)
AE 3 or above	−0.0234	0.0485	0.6290
Both-grade AEs*	−0.0178	0.0169	0.2920
No AE	0.0193	0.0104	0.0630
AE 1 or 2 (reference)	–	–	–
Treatment status
Ongoing	0.0559	0.0168	0.0001
Discontinued (reference)	–	–	–
Radiological progression (RECIST criteria)
Progression	−0.0228	0.0123	0.0645
No progression (reference)	–	–	–
First subsequent treatment post-discontinuation of study drug
Had a subsequent treatment	−0.0103	0.0039	0.7916
No subsequent treatment (reference)	–	–
Optimized multivariable analysis
Intercept	0.745	0.0201	–
BRCA status
Positive	−0.0316	0.0161	0.0511
Wild-type (reference)	–	–
Treatment status
Ongoing	0.0557	0.01673	0.0009
Discontinued (reference)	–	–

Notes:

* HSUVs recorded at the time a patient was experiencing both a grade 1–2 AE and a grade 3 plus AE were recorded as “Both-grade AEs”; all analysis based on a sample of 1,428 observations.

Abbreviations: OLS, ordinary least squares; BRCA, breast cancer antigen; AE, adverse event; RECIST, Response Evaluation Criteria in Solid Tumors; HSUVs, health-state utility values.

Table S1 Search terms used for identification of studies reporting health-state utility values

Search string	Number of citations identified	Description
1. “hui”	110,195	Study design facet to specify utility studies (and also expected to return HRQoL data) Adapted from National Institute for Health and Care Excellence (NICE),^Citation1 with additional terms sourced from Patient-Related Outcome and Quality-of-Life Instruments database (http://www.proqolid.org) The NICE report^Citation1 stated that “The search terms used in the review are extensive and appropriate” A validation of the search string was carried out, using results from the utility review reported as part of the manufacturers’ submission of bevacizumab.^Citation2 This review identified five sources of utility data. Four of these are captured by the search string used here. The study that was not captured was an RCT (RCTs relevant to the current utility review will be sourced from the clinical review in progress)
2. utilit^* AND mapping	4,243
3. “short form 36”/exp OR “sf36”/exp OR “sf-36”/exp OR “sf 36”/exp	10,094
4. “short form 12”/exp OR “sf12”/exp OR “sf-12”/exp OR “sf12”/exp	1,199
5. “short form 6” OR “sf6” OR “sf-6” OR “sf 6”	1,559
6. “euroqol” OR euro^*qol	2,794
7. “eq5d” OR “eq-5d” OR “eq 5d”	4,508
8. rosser	1,414
9. visual NEXT/1 analog^* AND analog^* NEXT/1 scale^*	45,013
10. eortc:ab,ti	7,457
11. “european organisation for research and treatment of cancer”:ab,ti OR “european organization for research and treatment of cancer”:ab,ti	2.820
12. “fact o”:ab,ti	34
13. “functional assessment of cancer therapy” AND (ovar^* OR “ovary”/exp	87
14. “health utilities” OR “health utility”	1,524
15. “multiattribute utility”	120
16. “utility value” OR “utility values”	1,014
17.“quality adjusted life year”/exp OR “quality adjusted life year”	11,560
18. “utility weights”	233
19. “utility weight”	35
20. “cost utilities”	16
21. “preference based hrqol”	25
22. “preference based health related quality of life”	51
23. “preference weights”	165
24.“quality adjusted life years”/exp OR “quality adjusted life years”	11,731
25. “qaly”/exp OR “qaly”	12,899
26. “time trade-off”	937
27. “standard gamble”	751
28. “cost utility”/exp OR “cost utility”	6,088
29. “cost utility analysis”/exp OR “cost utility analysis”	5,345
30. 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17 OR 18 OR 19 OR 20 OR 21 OR 22 OR 23 OR 24 OR 25 OR 26 OR 27 OR 28 OR 29	201,238
31. (ovar^* NEAR/5 (cancer^* OR neoplas^* OR carcinom^* OR malignan^* OR tumor^* OR tumour^*)):ab,ti	75,249	Disease facet to specify for ovarian cancer Adapted from the ovarian cancer-disease facet used by the three latest published Cochrane reviews in ovarian cancer^Citation3^–^Citation5
32. “ovary tumor”/exp	93,605
33. “ovary tumor”/exp OR (ovar^* NEAR/5 (cancer^* OR neoplas^* OR carcinom^* OR malignan^* OR tumor^* OR tumour^*)):ab,ti	107,189
34. 31 OR 32 OR 33	107,189
35. 30 AND 34 AND [humans]/lim AND [2003–2013]/py	946	Combined search string with limits to restrict to studies in humans, for publications published in the last 10 years

Abbreviations: HRQoL, health-related quality of life; RCT, randomized controlled trial.

Table S2 Variance–covariance matrix for the optimized multivariable analysis

	Intercept	BRCA status (+)	Treatment status (ongoing)
Intercept	0.0201	0	0
BRCA status (+)	−0.0066	0.0147	0
Treatment status (ongoing)	−0.0138	−0.006	0.0073

Abbreviation: BRCA, breast cancer antigen.

Table S3 Pearson correlation coefficients between sets of utility values generated by different algorithms

Visit	OLS vs Tobit	OLS vs Cheung	OLS vs Dobrez
All visits	0.915	0.878	0.736

Abbreviation: OLS, ordinary least squares.

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