Intended Use

The DETECT screening tool is designed to assist physicians screening patients with systemic sclerosis (SSc) with the goal of providing a recommendation as to which patients should be referred to echocardiography as a first step, and if applicable, for right heart catheterization as a second step for the diagnosis of pulmonary arterial hypertension (PAH).

The DETECT screening tool is limited for use by healthcare specialists who treat SSc patients, and who are familiar with PAH as a complication of SSc. It is not intended to replace the medical or professional judgment of healthcare providers.

Warnings and Precautions

It is not possible to determine the algorithm performance long term or to recommend how frequently patients should be screened, and the DETECT study included only patients with a diffusing capacity of the lungs for carbon monoxide (DLCO) of <60%.

Entering the wrong value of the parameters due to misunderstanding of the parameters can lead to the wrong risk score.

Instructions for use

The PAH risk calculator has been developed based on the DETECT Study. In this study, adults with SSc at increased risk of PAH underwent a broad panel of non-invasive assessments followed by diagnostic RHC.

Univariable and multivariable analyses selected the best discriminatory variables to screen for PAH. After assessment for clinical plausibility and feasibility, these were incorporated into a two-step, internally validated screening algorithm. Nomograms for clinical practice use were developed.

From an initial 112 variables, 8 were selected based on their discriminatory ability to screen for PAH. These formed the basis for constructing a screening algorithm consisting of two steps. Multivariable analysis resulted in six non-echocardiographic variables being included in Step 1 of the algorithm to determine the need for referral to echocardiography. Two echocardiographic variables were included in Step 2 in order to determine the need for referral for RHC.

The calculation of risk score of Step 1 and Step 2 can be illustrated based on the nomogram.

For Step 1, the points for each variable can be assigned by drawing a vertical line from the measured value of that variable to the points line. All variables contribute points irrespective of the measured value; eg, even a negative serum anticentromere antibody (ACA) will contribute 50 risk points. If one of the six values is missing, the total score can be calculated with only a minor impact on the model performance.

In this case the missing variable is assigned 50 points (except for the missing variable current/past telangiectasias, which is assigned 65 points). The Step 1 total risk score is calculated by adding together the points for each variable. If the Step 1 total risk score for your patient is greater than 300, referral for echocardiography is recommended.

For Step 2, the points for each variable (ie, the 2 echocardiography variables and the Step 1 total risk score) are assigned by drawing a vertical line from the value of that variable to the points line. The values for all Step 2 variables are required to calculate the Step 2 total risk score. If TR velocity cannot be determined because no TR is detectable upon echocardiography, 10 points should be assigned for TR velocity. The Step 2 total risk score is calculated by adding together the points for each variable. If the Step 2 total risk score for your patient is greater than 35, referral for right heart catheterization is recommended.

Step 1:

Enter the values of the following variables in the boxes provided:

• Forced vital capacity (FVC) % predicted / diffusing capacity of the lungs for carbon monoxide (DLCO) % predicted or FVC % predicted and DLCO % predicted separately
• Current/past telangiectasias
• Anticentromere antibody (ACA)
• N-terminal pro-brain natriuretic peptide (NT-proBNP)
• Serum urate
• Right axis deviation on electrocardiogram (ECG)

Click calculate to generate the Step 1 total risk score.

Step 1 total risk score is needed for Step 2 and must be saved if Step 2 will be performed in a different session (should Step 1 and 2 be performed in the same session, the Step 1 score will be automatically entered in Step 2). Step 1 results can be documented and filed as a PDF print-out, a PDF file saved on your computer, or manually in the hospital chart.

Missing variables

If one of the six variables in Step 1 was not obtained, the calculator can still be used and provides reliable results. The missing value is automatically imputed based on the DETECT data pool. If more than one variable is missing, the total risk score cannot be calculated.

Step 2:

Enter the values of the following variables in the boxes provided:

• Step 1 total risk score
• Right atrium area (cm²)
• Tricuspid regurgitant (TR) jet velocity or right ventricular systolic pressure (RVSP) (mmHg) and right atrial pressure (RAP) (mmHg)

Click “calculate” to generate the Step 2 total risk score.

Step 2 results can be documented and filed as a PDF print-out, a PDF file saved on your computer, or manually in the hospital chart.

Missing variables

All variables are needed for the Step 2 total risk score to be calculated. If TR velocity cannot be determined because no TR is detectable upon echocardiography (see tickbox "No measurable TR"), this does not count as a missing variable.

Performance of the PAH calculator

The DETECT algorithm, which is used in the PAH calculator, has the following performance value:

• Sensitivity: 92%
• Specificity: 49%

(This calculator uses a score-based cut-off as compared to the method reported in the DETECT Study publication, which uses a probability-based cut-off, resulting in slightly different sensitivity and specificity numbers)

Sensitivity and specificity are defined as follows:

• Sensitivity: Proportion of patients with RHC diagnosed PAH, correctly identified by the screening test using PAH calculator (True positives/[True positives + False negatives])
• Specificity: Proportion of patients without RHC diagnosed PAH, correctly identified by the screening test using PAH calculator (True negatives/[True negatives + False positives])

To avoid misunderstanding of the parameters used for calculation, there is an information icon for each parameter in Step 1 and Step 2. The corresponding parameter information will be displayed when the icon is clicked.

The allowed range of the parameters in Step 1 and Step 2 is defined as follows:

In case an out-of-range value is used as an input, the notification message box with an allowed range for the corresponding parameter will be displayed.

Please ensure that only the latest version of this app is used.

References:

Coghlan JG, Denton CP, Grünig E, Bonderman D, Distler O, Khanna D, Müller‑Ladner U, Pope JE, Vonk MC, Doelberg M, Chadha‑Boreham H, Heinzl H, Rosenberg DM, McLaughlin VV, Seibold JR; DETECT study group. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014 Jul;73(7):1340-9

Data on file, Janssen

Date of issue: December 2023

cp-232883v3

Actelion Pharmaceuticals US, Inc.