Content Validation of an Algorithm for the Assessment, Management and Monitoring of Drug-Induced QTc Prolongation in the Psychiatric Population

Figures & data

Figure 1 Schematic representation of the study design.

Table 1 Emerging Themes from the Interviews

Theme	Subthemes	Additional Remarks
Reliance on ECG readings	● Baseline and follow up ECG ● ECG monitoring	● ECG guides decision making ● Baseline ECG is essential for assessment ● ECG and symptoms-based monitoring for patients on QTc prolonging drugs ● Essential in all patients with clinical risk factors, history of CVD or on a QTc-prolonging drug
Clinically guided prescribing of QTc prolonging medications	● Patient’s clinical/medication histories ● Drug interactions ● Drug information resources ● Unawareness of specific drug-induced QTcI resources (Credible Meds) ● Clinical Pharmacists	● Use general drug-information references like Lexicomp, Up-to-date, BNF, Medscape, etc. ● Use of drug references is inconsistent, and mostly for general information purposes rather than for management ● Limited awareness of CredibleMeds^® ● Clinical pharmacist considered valuable, particularly for providing advice on management strategies
Assessment for QTc-prolongation	● History of QTc prolongation ● Medical and family history ● Physical signs and symptoms ● Clinical risk factors	● Signs and symptoms such as palpitations, syncope, dizziness, etc. ● Risk factors such as electrolyte abnormalities (ie hypokalemia and hypomagnesemia), arrhythmias, structural heart diseases, ischemic state, left ventricular dysfunction, etc. ● Family history (genetic pre-disposition)
Limited availability of protocols	● No specific guidelines ● Lack specific clinical protocol ● Limited awareness or use of risk assessment scoring tools	● Guidelines and references used include: Specific hospital-based ECG protocols and European Society of Cardiology guidelines ● No risk scoring used, either not aware or no time to undertake risk scoring ● Risk assessment is based on ECG, QTc prolongation, family history and symptoms

Figure 2 Reliability CVI scores of the QTcI Prolongation Algorithm. (A) presents the mean score of the appropriateness rating for each step of the algorithm in addition to the I-CVI. (B) presents the mean score for the safety of each step of the algorithm in addition to the I-CVI. (C) presents the mean score of the reliability of the references used in each step of the algorithm in addition to the I-CVI.

Abbreviations: CVI, Content validity index; QTcI, QTc interval prolongation; I-CVI, item level content validity index.

Table 2 Evaluation of the Appropriateness of Each Step in the QTcI Prolongation Algorithm

Decision Statement/Step	Mean	Mode (%)	I-CVI	SD	K*
1. Assessing the drug using CredibleMeds^®	3.33	3 (50.0)	0.92	0.65	0.92
2. Assessing the drug dose, route, and drug interactions	3.58	4 (58.3)	1	0.51	1
3. Estimating the patient’s QTcI prolongation risk	3.33	3 (50.0)	0.92	0.65	0.92
4. Assessing the need for ECG monitoring based on the QTcI prolongation risk score	3.67	4 (66.7)	1	0.49	1
5. Recommending therapy if QTcI prolongation risk score ≤ 7 points	3.08	3 (58.3)	0.83	0.67	0.83
6. Assessing baseline ECG if QTcI prolongation risk score ≥ 7 points	3.33	3 (50.0)	0.92	0.65	0.92
7. If ECG shows QTcI ≥ 500 ms, avoid therapy/consider cardiac consultation	3.67	4 (66.7)	1	0.49	1
8. If ECG shows QTcI ≤ 500 ms, recommend therapy with ECG follow up and physical examination in specific cases	3.42	3 (58.3)	1	0.51	1

Abbreviations: I-CVI, item-level content validity index; SD, standard deviation; QTc-I, corrected QT interval; ECG, electrocardiogram; ms, milliseconds; K*, modified kappa.

Table 3 Evaluation of the Safety of Each Step in the QTcI Prolongation Algorithm

Decision Statement/Step	Mean	Mode (%)	I-CVI	SD	K*
1. Assessing the drug using CredibleMeds^®	3.08	3 (58.3)	0.83	0.66856	0.83
2. Assessing the drug dose, route, and drug interactions	3.50	4 (58.3)	0.92	0.67420	0.92
3. Estimating the patient’s QTcI prolongation risk	3.33	3 (50.0)	0.92	0.65134	0.92
4. Assessing the need for ECG monitoring based on the QTcI prolongation risk score	3.50	4 (58.3)	0.92	0.67420	0.92
5. Recommending therapy if QTcI prolongation risk score ≤ 7 points	3.08	3 (58.3)	0.83	0.66856	0.83
6. Assessing baseline ECG if QTcI prolongation risk score ≥ 7 points	3.33	3 (50.0)	0.92	0.65134	0.92
7. If ECG shows QTcI ≥ 500 ms, avoid therapy/consider cardiac consultation	3.58	4 (58.3)	1	0.51493	1
8. If ECG shows QTcI ≤ 500 ms, recommend therapy with ECG follow up and physical examination in specific cases	3.42	3 (58.3)	1	0.51493	1

Abbreviations: I-CVI, Item-level content validity index; SD, standard deviation; QTc-I, corrected QT interval; ECG, electrocardiogram; ms, milliseconds; K*, modified kappa.

Table 4 Evaluation of the Reliability of the References Used in Each Step in the QTcI Prolongation Algorithm

Decision Statement/Step	Mean	Mode (%)	I-CVI	SD	K*
1. Assessing the drug using CredibleMeds^®	3.33	3 (50.0)	0.92	0.65134	0.92
2. Assessing the drug dose, route, and drug interactions	3.42	4 (50.0)	0.92	0.66856	0.92
3. Estimating the patient’s QTcI prolongation risk	3.42	4 (50.0)	0.92	0.66856	0.92
4. Assessing the need for ECG monitoring based on the QTcI prolongation risk score	3.42	3 (58.3)	1	0.51493	1
5. Recommending therapy if QTcI prolongation risk score ≤ 7 points	3.17	3 (50.0)	0.83	0.71774	0.83
6. Assessing baseline ECG if QTcI prolongation risk score ≥ 7 points	3.58	4 (66.7)	0.92	0.66856	0.92
7. If ECG shows QTcI ≥ 500 ms, avoid therapy/consider cardiac consultation	3.75	4 (75.0)	1	0.45227	1
8. If ECG shows QTcI ≤ 500 ms, recommend therapy with ECG follow up and physical examination in specific cases	3.42	3 (58.3)	1	0.51493	1

Abbreviations: I-CVI, Item-level content validity index; SD, standard deviation; QTc-I, corrected QT interval; ECG, electrocardiogram; ms, milliseconds; K*, modified kappa.

Figure 3 Word-cloud representation of survey open-ended responses.