Risk score development and data collection
Based on sensitivity and specificity results as well as the ability to
identify risk factors in the EHR, we built our risk score using the
components of the RISQ-PATH model5 by Vandael and
colleagues, with a few modifications to the lookback timeframe and
methods of extracting the data. Data extracted from the EHR and added to
the risk score included age, sex, body mass index (BMI,
kg/m2), cardiovascular history, liver failure,
neurological disorders, thyroid disturbances, potassium (mmol/L),
calcium (mmol/L), C-reactive protein (CRP; mg/L), estimated glomerular
filtration rate (eGFR; ml/min), and medications associated with a risk
of QTc-prolongation and/or TdP (lists 1, 2 and 3 of CredibleMeds).
CredibleMeds10 is an American organization that
provides lists of drugs associated with a risk of QTc-prolongation and
TdP (list 1: drugs with a known risk for TdP; list 2: drugs with a
possible risk for TdP; list 3: drugs with a conditional risk for TdP;
list 4: drugs to be avoided by patients with congenital long QT
syndrome, including all drugs in lists 1, 2 and 3, in addition to drugs
with special risk).
Table 1 lists the components included in our preliminary risk score.
Each risk factor is allocated a certain number of points contributing to
the total score, with a risk cutoff of 10 points. However, due to
limitations in the EHR, the score was unable to automatically extract a
previous ECG reading from the patient’s chart. This information was
collected manually through chart review and was not automatically
included in the risk score built in the EHR. The risk score and point
allocation were discussed with the cardiology department at MD Anderson
Cancer Center, who were in agreement with our methods and risk factors.
Details on how we extracted these components from the EHR are listed in
table A.1 (Supplementary appendix).
During the validation phase, each time a new QTc-prolonging medication
was signed or verified, the modified QTc-prolongation risk score was
calculated in the EHR and was saved in an archived file every 12 hours,
accessed solely by the investigators. The custom alert associated with
the score calculation was not visible during the validation phase. The
current DDI warnings that triggered at the time of risk score
calculation were saved in a separate file and retrieved by the
investigators. A chart review was conducted on patients who met the
inclusion criteria to validate the risk score and compare it to the
current DDI warnings. QTc intervals were collected manually using
baseline and follow-up 12-lead ECG readings, and were corrected using
the Fridericia formula (QTcF). We defined a prolonged QTc interval as ≥
450 ms for males, ≥ 470 ms for females, or an increase from baseline by
≥ 30 ms.
Table 1. Preliminary QTc-prolongation risk score at MD Anderson
Cancer Center