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National Lung Screening Trial (NLST) Screening (NLST)

This study has been completed.
Sponsor:
Collaborator:
American College of Radiology Imaging Network
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00047385
First received: October 3, 2002
Last updated: May 2, 2014
Last verified: October 2012
Results First Received: May 30, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Screening
Condition: Lung Cancer
Interventions: Device: low-dose helical computed tomography
Device: chest radiography

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was from August 2002 through April 2004 at 33 NLST sites.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants signed a study informed consent prior to being randomized to a study arm.

Reporting Groups
  Description
Low-Dose CT Participants undergo low-dose helical CT examination.
Chest X-ray Participants undergo chest x-ray examination.

Participant Flow:   Overall Study
    Low-Dose CT   Chest X-ray
STARTED   26722   26732 
COMPLETED   26455 [1]   26232 
NOT COMPLETED   267   500 
Death before any screening                2                5 
Lung Cancer diagnosed before screening                5                3 
Eligible for screening but had no screen                260                492 
[1] Had at least one screening exam.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Low-Dose CT Participants undergo low-dose helical CT examination.
Chest X-ray Participants undergo chest x-ray examination.
Total Total of all reporting groups

Baseline Measures
   Low-Dose CT   Chest X-ray   Total 
Overall Participants Analyzed 
[Units: Participants]
 26722   26732   53454 
Age 
[Units: Participants]
     
<=18 years   0   0   0 
Between 18 and 65 years   19612   19622   39234 
>=65 years   7110   7110   14220 
Age 
[Units: Years]
Mean (Standard Deviation)
 61.4  (5.0)   61.4  (5.0)   61.4  (5.0) 
Gender 
[Units: Participants]
     
Female   10952   10970   21922 
Male   15770   15762   31532 
Region of Enrollment 
[Units: Participants]
     
United States   26,722   26,732   53454 


  Outcome Measures
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1.  Primary:   Lung Cancer Deaths   [ Time Frame: All events through December 31, 2009; median follow-up 6.5 years. ]

Measure Type Primary
Measure Title Lung Cancer Deaths
Measure Description Lung cancer deaths confirmed in participants by Endpoint Verification if available, otherwise by death certificate.
Time Frame All events through December 31, 2009; median follow-up 6.5 years.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed. An intention-to-treat analysis was performed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
   LDCT Screening   CXR Screening 
Participants Analyzed 
[Units: Participants]
 26722   26732 
Lung Cancer Deaths 
[Units: Participants]
 356   443 


Statistical Analysis 1 for Lung Cancer Deaths
Groups [1] All groups
Method [2] Weighted log-rank (details below)
P Value [3] 0.004
Hazard Ratio (HR) [4] 0.800
95% Confidence Interval 0.733 to 0.932
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Alternative hypothesis: LDCT screening reduces lung cancer mortality relative to chest x-ray.

Power: 90% for a 20% reduction in lung cancer mortality.

[2] Other relevant method information, such as adjustments or degrees of freedom:
  Weights in weighted log-rank statistic increased linearly from zero at randomization to full weight at 4 years and thereafter.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  P-value is adjusted for multiple comparisons.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Deaths From All Causes in All Randomized Participants.   [ Time Frame: All events through December 31, 2009; median follow-up 6.5 years. ]

Measure Type Secondary
Measure Title Deaths From All Causes in All Randomized Participants.
Measure Description Deaths from all causes were compared between the low-dose CT group and the chest radiography group among all randomized participants.
Time Frame All events through December 31, 2009; median follow-up 6.5 years.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed. An intention-to-treat analysis was performed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
   LDCT Screening   CXR Screening 
Participants Analyzed 
[Units: Participants]
 26722   26732 
Deaths From All Causes in All Randomized Participants. 
[Units: Participants]
 1877   2000 


Statistical Analysis 1 for Deaths From All Causes in All Randomized Participants.
Groups [1] All groups
Method [2] Weighted log-rank (details below)
P Value [3] 0.02
Hazard Ratio (HR) [4] 0.933
95% Confidence Interval 0.864 to 0.988
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Alternative hypothesis: LDCT screening reduced all-cause mortality relative to chest x-ray.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Weights in weighted log-rank statistic increased linearly from zero at randomization to full weight at 4 years and thereafter.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No adjustment for multiple comparisons. Only one analysis performed.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Lung Cancer Diagnoses   [ Time Frame: All events through December 31, 2009; median follow-up 6.5 years ]

Measure Type Secondary
Measure Title Lung Cancer Diagnoses
Measure Description Lung cancer diagnoses confirmed by medical record abstraction.
Time Frame All events through December 31, 2009; median follow-up 6.5 years  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed. An intention-to-treat analysis was performed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
   LDCT Screening   CXR Screening 
Participants Analyzed 
[Units: Participants]
 26722   26732 
Lung Cancer Diagnoses 
[Units: Participants]
 1060   941 


Statistical Analysis 1 for Lung Cancer Diagnoses
Groups [1] All groups
Hazard Ratio (HR) [2] 1.13
95% Confidence Interval 1.03 to 1.23
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  Denominator: LDCT Group Numerator: CXR Group



4.  Secondary:   Complications of Diagnostic Evaluation Following a Positive Screening Test.   [ Time Frame: One year from screening examination ]

Measure Type Secondary
Measure Title Complications of Diagnostic Evaluation Following a Positive Screening Test.
Measure Description Number of participants who experienced complications during diagnostic work-up of a screening CT or CXR that was suspicious for lung cancer.
Time Frame One year from screening examination  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The units analyzed were positive screening exams with documented diagnostic follow-up. If participant received 3 positive screens with documented follow-up after each one, he/she would be counted 3 times in the number of units analyzed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
   LDCT Screening   CXR Screening 
Participants Analyzed 
[Units: Participants]
 26722   26732 
Units Analyzed (Positive Screens with Follow-up) 
[Units: Positive Screens with Follow-up]
 17702   4953 
Complications of Diagnostic Evaluation Following a Positive Screening Test. 
[Units: Pos. screens w/ complications]
 245   81 

No statistical analysis provided for Complications of Diagnostic Evaluation Following a Positive Screening Test.



5.  Secondary:   T0 (Baseline) Screening Results   [ Time Frame: T0 (at study entry) ]

Measure Type Secondary
Measure Title T0 (Baseline) Screening Results
Measure Description Results of radiologist's interpretation of images from LDCT or CXR screening exam at T0.
Time Frame T0 (at study entry)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed.

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
   LDCT Screening   CXR Screening 
Participants Analyzed 
[Units: Participants]
 26722   26732 
T0 (Baseline) Screening Results 
[Units: Participants]
   
Positive   7191   2387 
Significant abnor. not suspicious for lung cancer   2695   785 
No, or minor abnormality   16423   22863 
Eligible but not screened   406   689 
Not eligible for screen   7   8 

No statistical analysis provided for T0 (Baseline) Screening Results



6.  Secondary:   T1 Screening Results   [ Time Frame: T1 (one year after entry) ]

Measure Type Secondary
Measure Title T1 Screening Results
Measure Description Results of radiologist's interpretation of images from LDCT or CXR screening exam at T1. Includes a comparison with images from T0 screen.
Time Frame T1 (one year after entry)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
   LDCT Screening   CXR Screening 
Participants Analyzed 
[Units: Participants]
 26722   26732 
T1 Screening Results 
[Units: Participants]
   
Positive   6901   1482 
Significant abnor. not suspicious for lung cancer   1519   429 
No, or minor abnormality   16295   22178 
Eligible but not screened   1570   2321 
Not eligible for screen   437   322 

No statistical analysis provided for T1 Screening Results



7.  Secondary:   T2 Screening Results   [ Time Frame: T2 (two years after entry) ]

Measure Type Secondary
Measure Title T2 Screening Results
Measure Description Results of radiologist's interpretation of images from LDCT or CXR screening exam at T2. Includes a comparison with images from T0 and T1 screens.
Time Frame T2 (two years after entry)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants randomized were analyzed

Reporting Groups
  Description
LDCT Screening Participants randomized to receive three annual low-dose helical CT exams of the chest.
CXR Screening Participants randomized to receive three annual chest radiographs.

Measured Values
   LDCT Screening   CXR Screening 
Participants Analyzed 
[Units: Participants]
 26722   26732 
T2 Screening Results 
[Units: Participants]
   
Positive   4054   1174 
Significant abnor. not suspicious for lung cancer   1408   361 
No, or minor abnormality   18640   21811 
Eligible but not screened   1840   2764 
Not eligible for screen   780   622 

No statistical analysis provided for T2 Screening Results




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
NLST utilized institutions with special expertise. The "healthy volunteer" effect may apply. Scanners are now more technologically advanced. Ongoing LDCT screening may reduce the rate of lung cancer deaths more than three rounds done in NLST.


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