Specifying exposure classification parameters for sensitivity analysis: family breast cancer history

Figures & data

Table 1 Validation studies that reported sensitivity and specificity values for self-reported first-degree relative’s breast cancer history

Authors	Breast cancer cases		Healthy noncases		Source population	“Gold standard” measurement tool(s)
	Sensitivity (No./Total) (95% CI)	Specificity (No./Total) (95% CI)	Sensitivity (No./Total) (95% CI)	Specificity (No./Total) (95% CI)
Chang et al^Citation20	–	–	0.72 (61/85) (0.62, 0.81)	0.99 (1114/1127) (0.98, 0.99)	Sweden	Swedish Cancer Registry
Kerber and Slattery^Citation34	0.85 (11/13) (0.55, 0.98)	0.96 (107/112) (0.90, 0.99)	0.82 (18/22) (0.60, 0.95)	0.91 (167/184) (0.87, 0.95)	Utah, USA	Utah Population Database
Soegaard et al^Citation21	–	–	0.94 (121/129) (0.90, 0.98)	1.00 (4505/4527) (0.99, 1.00)	Denmark	Danish Cancer Registry
Verkooijen et al^Citation35	0.98 (60/61) (0.91, 1.00)	0.99 (247/249) (0.97, 1.00)	–	–	Geneva, Switzerland	Cantonal Population Office and Geneva Cancer Registry
Ziogas and Anton-Culver^Citation36	0.95 (188/197) (0.93, 0.98)	0.97 (850/873) (0.96, 0.98)	–	–	Orange County, California, USA	Pathology, self-reported, or death certificates

Abbreviation: CI, confidence interval.

Table 2 Single point-estimate values for classification errors and nonprobabilistic sensitivity analysis results

Scenario	Breast cancer cases		Healthy noncases		OR adjusted
	Sensitivity	Specificity	Sensitivity	Specificity
1a	1.00	1.00	1.00	1.00	1.63
2	0.85	0.96	0.82	0.91	6.67
3	0.98	0.99	0.72	0.99	1.19
4	0.95	0.97	0.72	0.99	1.08
5	0.98	0.99	0.94	1.00	1.46
6	0.95	0.97	0.94	1.00	1.33
7	0.85	0.96	0.72	0.91	5.73
8	0.98	0.99	0.94	1.00	1.47
9b	0.92	0.98	0.93	0.99	1.61
10	0.98	0.96	0.72	1.00	0.87
11	0.85	0.99	0.94	0.91	9.62

Notes:

a Crude odds ratio scenario;

b Approximately nondifferential.

Abbreviation: OR _adjusted, odds ratio adjusted for family breast cancer history (exposure) misclassification.

Table 3 Descriptions of the probability distributions used for exposure classification errors

Scenario	Breast cancer cases		Healthy noncases
	Sensitivity	Specificity	Sensitivity	Specificity
12	Custom uniforma (1.00)	Custom uniform (1.00)	Custom uniform (1.00)	Custom uniform (1.00)
13	Uniformb (0.85, 1.00)	Uniform (0.96, 1.00)	Uniform (0.72, 1.00)	Uniform (0.91, 1.00)
14	Triangularc (0.85, 0.95, 1.00)	Triangular (0.96, 0.97, 1.00)	Triangular (0.72, 0.82, 1.00)	Triangular (0.91, 0.99, 1.00)
15	Triangular (0.85, 0.93, 1.00)	Triangular (0.96, 0.97, 1.00)	Triangular (0.72, 0.83, 1.00)	Triangular (0.91, 0.97, 1.00)

Notes:

a Discrete uniform distribution with a single value at 1.00 with probability of occurring = 1;

b Continuous uniform distribution (minimum value, maximum value);

c Triangular distribution (minimum value, mode, maximum value).

Table 4 2 × 2 tablea after adjustment for exposure misclassification

Breast cancer outcome	Any first-degree family breast cancer history		Odds ratio adjusted for exposure misclassification
	Yes	No
Breast cancer cases	$e=\frac{a-(1-{\mathit{\text{Sp}}}_{\mathit{\text{cases}}})(a+b)}{{\mathit{\text{Se}}}_{\mathit{\text{cases}}}+{\mathit{\text{Sp}}}_{\mathit{\text{cases}}}-1}$	f = a + b − e	${\mathit{\text{OR}}}_{\mathit{\text{adjusted}}}=\frac{e\cdot h}{f\cdot g}$
Breast cancer noncases	$g=\frac{c-(1-{\mathit{\text{Sp}}}_{\mathit{\text{noncases}}})(c+d)}{{\mathit{\text{Se}}}_{\mathit{\text{noncases}}}+{\mathit{\text{Sp}}}_{\mathit{\text{noncases}}}-1}$	h = c + d − g

Notes:

a a, breast cancer cases classified as having a first-degree family breast cancer history; b, breast cancer cases classified as not having a first-degree family breast cancer history; c, breast cancer noncases classified as having a first-degree family breast cancer history; d, breast cancer noncases classified as not having a first-degree family breast cancer history;

Abbreviations: OR, odds ratio; Se, sensitivity; Sp, specificity.

Figure 1 Frequency distributions of breast cancer odds ratios adjusted for family breast cancer history misclassification, by scenario.

Figure 2 Frequency distributions of breast cancer odds ratios adjusted for family breast cancer history misclassification and random error, by scenario.

Table 5 Probabilistic sensitivity analyses resultsa after 50,000 simulation trials, by scenario

Scenario	Analysis	ORadjusted geometric mean	ORadjusted median	95% uncertainty limits for ORadjusted	% of trials with ORadjusted > crude ORb	Ratio of upper 95% uncertainty limit to lower 95% uncertainty limit
12c	a. No misclassification	1.63	1.63	(1.63, 1.63)	0	1.00
	b. Conventional analysis (random error only)	1.63	1.63	(1.34, 1.99)	50.6	1.49
13	a. Misclassification only	2.46	2.25	(1.41, 5.88)	84.4	4.17
	b. Misclassification and random error	2.46	2.27	(1.33, 6.01)	83.3	4.52
14	a. Misclassification only	1.89	1.74	(1.36, 3.84)	62.5	2.82
	b. Misclassification and random error	1.89	1.77	(1.25, 3.93)	64.0	3.14
15	a. Misclassification only	2.09	1.96	(1.46, 4.13)	85.0	2.83
	b. Misclassification and random error	2.09	1.99	(1.37, 4.21)	81.8	3.07

Notes:

a Correlation between the sensitivities for cases and noncases and between the specificities for cases and noncases = 0.80;

b Crude odds ratio = 1.63;

c Crude odds ratio scenario.

Abbreviation: OR _adjusted, Odds ratio adjusted for family breast cancer history (exposure) misclassification.

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