Critical appraisal:Gareen IF, Duan F, Greco EM, Snyder BS, Boiselle PM, Park ER, et al 2014

participants were invited to complete HRQoL forms at baseline and asked to provide contact information.
those participants who had baseline HRQoL assessments and had a positive screen result were recruited.
In the second year of the study, participants with results “negative for lung cancer, but positive for significant
incidental findings (SIFs)were also invited.

were then asked to complete the Short Form-36 and the State Trait Anxiety Inventory (form Y-1) questionnaires to assess short-term (1 month) and longterm (6 months) effects of screening.

ACRIN enrolled
all participants with a at these sites, whose results had been received at the
Biostatistics Center within 30 days of the screening examination,
who had completed the baseline HRQoL forms,

and who had provided contact information, for this study.

Reported outcome(s):

measures:
1. Global health status (Short Form SF-36 v 2.0 (SF-36)), a measure of physical and mental
function, administered at baseline, 1 month and 6 months
2. State Anxiety (Spielberger State Trait Anxiety Inventory ) administered at 1 month and 6 months

comparisons:
1. PCS difference from baseline to 1 month and 6 months
2. MCS difference from baseline to 1 month and 6 months
3. STAI at 1 month and 6 months

adjusted for a priori potential confounders and matching factors, including, the number of prior screens with a SIF, number of prior screens suspicious for lung cancer, study site, age, sex, education, marital status, smoking status, race, ethnicity

SF-36 is a 36-question health survey. These 36 questions are used to derive 8 profiles of functional health and
well-being. Physical health is measured by the Physical Functioning, Role-Physical, Bodily Pain, and General
Health scales. Mental health is described by the Vitality, Social Functioning, Role-Emotional, and Mental Health
scales. Because it is often easier to report information on fewer, less detailed parameters, these 8 health dimensions
are used to derive 2 summary measures, a Physical Component Score (PCS) and a Mental Component Score MCS).

The PCS and MCS range from 0 to 100, with a mean of 50 and a standard deviation of 10. For each of the SF-36 scale parameters and summary scores, lower scores indicate lower HRQoL.

For adults aged 55-64, the median norm PCS is 50.65 and MCS is 55.28. For adults 65-74, the median norm PCS is 46.11 and MCS is 56.11. A change of 3 to 5 points in either of the SF-36 component scores across groups or over time is widely accepted as a clinically important change.

STAI Form Y-1, a 20-question measure. Scores range from 20 to 80, with higher scores indicating higher levels of state anxiety. The median norm for working adults aged 50 to 69 years is 34.51 for men and 32.20 for women. A difference between 2 groups with different exposures of one standard error is generally considered to represent a small effect, one and one half standard errors to represent a moderate effect, and two standard errors to represent a large effect

We elected to measure HRQoL and anxiety after 1 month to assess short-term effects at a time proximal to the screen, but far away enough that participants should have received their results. Per the ACRIN/NLST protocol, participants
were to be informed of their screening results within 4 weeks of the screening test. We measured these indices
again after 6 months to assess the longer-term impact of the screening results.

we divided screen results into “false positive,” “true positive,” “SIF,” and “negative.”

Results of outcome(s):

2812 participants met our study entry criteria and were invited to participate in this study. The index screen was T0 for 1450 participants, T1 for 923, and T2 for 439 .

HRQoL study participants were similar with respect to age distribution and smoking status to the remainder of the NLST population; however, HRQoL participants, were more likely to be female, white, non-Hispanic, more educated, and unmarried.

1087 participants had screen results suspicious for lung cancer; 1024 were categorized as false positive and 63 were true-positive.

A total of 2317 participants (82.4%) completed forms within 45 days of mailing for the 1-month time point, and 1990 (70.8%) for the 6-month time point. At the time of completion of the 1-month questionnaire, 2126 (91.8%) knew their screening result. At 6 months, all participants knew their screening result.

Anxiety was substantially higher and physical and mental health scores significantly lower among those in the true-positive group compared with the false positive, SIF, and negative groups in crude and adjusted analyses at 1 and 6 months after screening. There was no difference in state anxiety or PCS or MCS by screening arm [LDCT or CXR].

Comments on results:

participants received extensive counseling as part of the consent process (ACRIN advised participants that up to 50% of those screened might receive a screen result suspicious for lung cancer, even though the participants did not have lung cancer, and that as many as 20% to 50% of those participants would require additional imaging or other testing to
confirm that findings initially thought to be of concern were not cancer).

This is also the first report of the effect of SIF findings on HRQoL and anxiety following lung screening.

we did not administer lung cancer–specific measures in the NLST due to concerns regarding participant burden (cf NELSON)

HRQoL participants, were more likely to be female, white, non-Hispanic, more educated, and unmarried than NLST participants in general.

return rate at 6 months was 70% compared to 82% at 1 month.

Includes an economic evaluation

no

Evidence ratings

Level of evidence

II

Risk of bias

Moderate risk of bias

Comments: Please replace this text and include any additional comments in regards to your quality rating

Show/Hide Risk of bias assessment

Risk of bias assessment: randomised controlled trial

Was the trial double-blinded?

Outcomes not blinded, substantial side-effects, or not reported.

Was the treatment allocation schedule concealed?

Adequately concealed (e.g. central randomisation, numbered or coded bottles, drugs prepared by pharmacy).

Were all randomised participants included in the analysis?

Too many exclusions, differential loss in comparison groups, or not reported.

The field below is not considered when calculating the risk of bias rating

How was the allocation schedule generated?

Adequate (e.g. random number table, computer random generator, coin tossing, card shuffling)

Size of effect

1	Reason for decision: Please replace this text and briefly describe the reasons for your rating

Relevance of evidence

1	Additional comments: Please replace this text and briefly describe the reasons for your rating

Result of appraisal

Included

Completed by

Dr Henry Marshall FRACP