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BRIEF REPORT
Ahead of print publication  

Knowledge on hydroxychloroquine prescription and attitude toward its use in COVID-19 – A survey-based study among doctors


1 Department of Dermatology, IQRAA International Hospital and Research Centre, Kerala, India
2 Department of Psychiatry, IQRAA International Hospital and Research Centre, Kerala, India
3 Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
4 Department of Rheumatology, IQRAA International Hospital and Research Centre, Kerala, India
5 Department of Health and Family Welfare, Kerala, India

Date of Submission15-Jul-2020
Date of Acceptance07-Sep-2020

Correspondence Address:
T Muhammed Razmi,
IQRAA International Hospital and Research Centre, IQRAA International Hospital and Research Centre, IQRAA Aesthetics, Address Mall, Calicut, - 673 001, Kerala
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_184_20

  Abstract 


Background: The use of hydroxychloroquine (HCQ) in COVID-19 had garnered enormous media attention. There were conflicting reports as well as unscientific opinion pieces in the scientific literature also. This study was planned to assess the knowledge, attitude, and practice of health-care professionals regarding HCQ.
Methods: An online survey was created with 8 knowledge-based questions (n = 2 fact-based [each scoring 1], n = 6 guideline-based [each scoring 2]), and 6 attitude-based questions, and distribution among a target population of doctors was done using Google™ forms.
Results: Of 115 respondents, the majority considered HCQ a safe drug (86.1%) and were in favor of its usage in COVID-19 trials (81.7%) or health-care/contact prophylaxis (60.9%) but against its use as a mass prophylactic agent (80.9%). Contrary to the published guidelines/recommendations, 80% and 55.7% of respondents opined for routine cardiac and glucose-6-phosphate dehydrogenase evaluations before prescribing HCQ. Those who were dealing with COVID-19 patients directly (n = 41) had significantly lower knowledge score compared to the others (6.37 vs. 7.72, P = 0.007). They had significantly lesser awareness for the baseline tests recommended (97.6% vs. 77.0%, P = 0.003). A significantly higher number of these physicians opposed the use of HCQ in clinical trials (26.82% vs. 8.1%, P = 0.027) and health-care/contact prophylaxis (41.5% vs. 16.2%, P = 0.008).
Conclusion: Sparse and speedily gathered information on HCQ can influence the practicing doctors, especially those involved directly in COVID-19 patient care, but less familiar with the prescription of this time-tested drug. Possibly, this has a bearing on the counseling of the patients requiring HCQ for non-COVID-19 indications and formulation of new guidelines.

Keywords: Attitude, COVID-19, doctors, hydroxychloroquine, knowledge, physician, survey



How to cite this URL:
Afra T P, Uvais N A, Bishnoi A, Sukesh E, Eliyas S, Bishurul Hafi N A, Razmi T M. Knowledge on hydroxychloroquine prescription and attitude toward its use in COVID-19 – A survey-based study among doctors. Indian J Rheumatol [Epub ahead of print] [cited 2020 Oct 30]. Available from: https://www.indianjrheumatol.com/preprintarticle.asp?id=298047




  Introduction Top


The rapidity and impact of COVID-19 pandemic, coupled with the lack of an effective antiviral or vaccine, led to the policymakers adopting strategies based on available evidence. One such strategy was the use of hydroxychloroquine (HCQ) as a therapeutic agent in COVID-19-affected patients and as a prophylactic agent in frontline health-care workers or contacts of COVID-19-positive individuals.[1]

Though the use of HCQ in COVID-19 care had not been substantiated initially by the scientific evidence, the massive media attention and endorsement by influential leaders on its use in COVID-19 had led to the rampant use of HCQ by otherwise healthy individuals (some of them used nonpharmaceutical chloroquine phosphate[2] and at an improper dosage), unmasking its rare side effects into the limelight. This had prompted regulatory agencies to issue precautionary warnings about its possible “rare” side effects.[3] This was also followed by several opinion pieces in scientific literature cautioning about its adverse effects;[4],[5] many of these were not based on scientific evidence.[6],[7] Such reports possibly have influenced physicians' understanding and knowledge of this time-tested drug.[4] Herein, we describe the results of an online survey that aimed to assess the knowledge of doctors regarding HCQ prescription and their opinion on the use of HCQ in the fight against COVID-19.


  Methods Top


The online survey (snowball technique) using Google™ forms was conducted between April 25 and May 1, 2020. The institutional review board had exempted ethical committee clearance for the survey study. Apart from the profile inquiries, the survey had 8 knowledge-based questions and 6 attitude-based questions. A score of 1 was given for fact-based knowledge question (n = 2), whereas practice/guideline-based knowledge questions (n = 6) were allocated a score of 2 (total score = 14). Response to the attitude-based questions was grouped either into yes/no or favoring/opposing/no opinion [questionnaire in Supplement 1]. The questionnaire was formulated by ATP and MRT and finalized after getting inputs from experts (NAU, AB, and ES) in the field.

The statistical analysis was carried out using the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA, version 22.0 for Windows). All quantitative variables were summarized using measures of central tendency (mean and median) and measures of dispersion (standard deviation and interquartile range) depending on the type of distribution. Normality was assessed by plotting histogram and stem and leaf plots. All qualitative variables were summarized as proportions. Total knowledge scores between different groups were compared using the Student's t-test, whereas attitude-based responses were compared using the Chi-square test or Fisher's exact test. All statistical tests were two-sided and performed at a significance level of P < 0.05.


  Results Top


The basic details of the sample population are given in [Table 1]. We got 115 responses at the end of the study. Of these, 96/115 were practicing clinicians, and 41/115 were directly involved in COVID-19-related patient care services or research. The majority (106/115) had a master's degree and above, and around half of the responders (55/115) belonged to the specialties familiar with HCQ prescription (dermatology, rheumatology, and internal medicine). Only 9/115 resorted to referring resources to answer the survey.
Table 1: Survey - Descriptive data regarding subject profile and knowledge-based questions

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Regarding the attitude [Table 2], though the majority considered HCQ a safe drug (99/115, 86.4%), only a minority (20/115, 17.1%) were convinced with its antiviral effects. Still, most of the participants were in favor of this drug being used in various COVID-19 trials (94/115, 81.7%) or health-care prophylaxis (70/115, 60.9%). Its use as a mass prophylactic agent was opposed by the majority (93/115, 80.9%).
Table 2: Comparison of total knowledge score with the attitude and relevant subject profile details

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Majority (74.8%) had prescribed HCQ in their practice, though not routinely. Most of the respondents opined for routine cardiac (92/115, 80%) and G6PD (64/115, 55.7%) evaluations before prescribing HCQ. Only 18/115 (15.7%) correctly answered ophthalmology screening alone as the response. Only 37.4% correctly responded vision defects as the only contraindications among the options given. The possibility of rare serious cutaneous adverse effects with HCQ was not known to 41.7%. All of the respondents were aware of HCQ being an antimalarial, and 87.8% rightly mentioned about the immunomodulatory action of it. The majority (113/115) agreed on the possibility of rare cardiac events in certain scenarios only. A significant number of respondents (45.2%) opined that ocular toxicity with HCQ develops within a year of drug initiation (c. f correct response [after 5 years] recorded by 41.7%), and only 19.1% correctly mentioned the frequency of ophthalmologic follow-up evaluations (annually after 5 years of drug initiation).

The mean total knowledge score (max = 14) of the respondents was 7.23 (range, 3–14). The score was higher in the specialties where HCQ is regularly being prescribed (rheumatology – 10.67, dermatology – 8.35, internal medicine – 6.87, and other specialties – 6.53) [Table 2]. The mean total score was higher in those who opposed mass prophylaxis (the majority) compared to those who favored this practice (7.47 vs. 5.29, P = 0.036). Similarly, those who opined it as a safe drug (the majority) had a better mean score than those who considered it as an unsafe drug (7.49 vs. 5.75, P = 0.026) [Table 2].

Those who were dealing with COVID-19 patients directly had significantly lower scores compared to the others (6.37 vs. 7.72, P = 0.007), important domains being significantly inaccurate awareness for the baseline tests (40/41, 97.6% vs. 57/74, 77.0%, P = 0.003), the possibility of rare serious cutaneous side effects (24/41, 58.5% vs. 24/74, 32.4%, P = 0.007), and frequency of follow-up ophthalmologic evaluations (38/41, 92.7% vs. 58/74, 78.4%, P = 0.048). A significantly higher number of them relatively opposed the use of HCQ in clinical trials (11/41, 26.82% vs. 6/74, 8.1%, P = 0.027), and health-care/contact prophylaxis (17/41, 41.5% vs. 12/74, 16.2%), P = 0.008). Conversely, those who had personally taken HCQ as a prophylaxis agent relatively favored its use in COVID-19 circumstances including mass prophylaxis [Table 3].
Table 3: Variables in the individual profile and knowledge-related response that found significantly influenced the key attitude-related queries on hydroxychloroquine use in COVID-19

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  Discussion Top


The survey highlights the inadequate knowledge of physicians, especially those who are in frontline COVID-19 care, on HCQ prescription and contraindications, and its bearing on their attitude toward its use in COVID-19 care. Information on antiviral effects of HCQ emerged during the previous SARS pandemic and heightened only during the recent COVID-19 pandemic.[8] The majority of the respondents who favored its use in COVID-19 trials and health-care prophylaxis considered it as a safe drug but were not convinced about its antiviral effects. Most of the respondents were against its use as a mass prophylactic agent, thus against its indiscriminate use by the public. Relatively favoring response of those who had personally taken HCQ toward various COVID-19 prophylaxes exemplifies the knowledge–attitude–practice concept.

Interestingly, the majority of the respondents opined initial cardiac evaluation as a requirement, and more than half of them considered baseline G6PD evaluation as a necessary baseline investigation before starting HCQ. None of the prior rheumatology guidelines consider initial cardiac evaluation as a requirement before starting HCQ[9] (with some even suggesting its protective effects against conduction abnormalities in lupus patients, especially those with anti-Ro antibodies and neonatal lupus).[10],[11] COVID-19, being a disease with significant cardiopulmonary involvement, the Mayo clinic has recommended baseline ECG monitoring of “COVID-19 patients” before starting HCQ.[12] However, a recent systematic review of quinolone antimalarials did not report any serious cardiac adverse events.[13] A large cohort of COVID-19 patients treated with chloroquine/HCQ ± azithromycin also showed similar results.[14] We fear that future rheumatology/dermatology guidelines may also resort to having an initial cardiac evaluation, not because of the sound evidence from >50 years of HCQ use, but because of the recent “noise”[15] in the context of its use in COVID-19.

The “belief” of HCQ causing hemolysis in G6PD deficients is unfounded by the scientific evidence.[16] Despite a recent meta-analysis not demonstrating a significant drop in hemoglobin from baseline in G6PD deficients with the use of chloroquine monotherapy,[17] the US Food and Drug Administration considers G6PD evaluation as a necessary baseline test to be done.[3] Many recent editorials and opinion pieces cautioned the possibility of HCQ-induced hemolysis in G6PD deficients, who are possibly more prone to COVID-19 infections.[5],[6] A recent report[18] on doubtful precipitation of hemolysis in a G6PD-deficient COVID-19 patient was challenged by others[7] for the absence of supporting evidences.

Only one-third of the respondents rightly mentioned the presence of visual defects as a true contraindication for HCQ, whereas others opined pregnancy (47.8%) and childhood (43.5%) as contraindications for HCQ use, despite the presence of long-term safety data on the use of HCQ in these populations.[19] Notably, those directly involved in COVID-19 care had significantly lesser awareness of the existing HCQ guidelines and significantly opposed its use in COVID-19 circumstances. This may be due to the dermatologists and rheumatologists, who prescribe HCQ more often in routine circumstances and possibly have a more accurate basic understanding regarding HCQ were less likely to be directly involved in COVID-19 frontline care. However, inaccurate answers provided even by these specialists (total knowledge score: rheumatology – 10.67/14 and dermatology– 8.35/14) highlight the need for continuing medical education on HCQ prescription and monitoring.

The snowball sampling limited the study by the possible selection bias. The study questionnaire was not a validated one; hence, the total knowledge score assessed by this survey might not represent the actual knowledge of doctors on the subject. However, by allocating a differential score to fact-based and guideline-based questions, we tried to gauge the practical knowledge of doctors regarding HCQ prescription.

In summary, the current controversies on HCQ use in COVID-19 have possibly influenced the doctors, especially those who are directly involved in the care of COVID-19 patients. The knowledge, even if it is unfounded by scientific evidence, has a bearing on these clinicians' perspectives on the use of HCQ in COVID-19. We fear that an inadequate and inaccurate knowledge (which seems to be an outcome of the renewed interest in this time-tested drug on a backdrop of sparse and speedily gathered evidence on its efficacy in COVID-19) may influence the existing treatment guidelines for rheumatological–dermatological–infectious disease indications. Furthermore, convincing newly diagnosed rheumatology and dermatology patients regarding the risk–benefit ratio of the HCQ will be now more challenging than the pre-COVID era.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Supplement

Supplement 1: Google™ survey form questionnaire

5/28/2020 Survey to assess hydroxychloroquine use among doctors during COVID-19 pandemic.

Survey to assess hydroxychloroquine use among doctors during COVID-19 pandemic.



This is an online survey on hydroxychloroquine use among doctors, in light of the renewed global interest in it. There is debate on its usefulness in COVID-19 and its potential side effects if it used as a mass prophylaxis drug. The survey also aims to gauge the physician's understanding of the safety and efficacy of this drug.

By continuing with this survey, you are agreeing to collect the answers you entered for the scientific data analysis purposes. This survey is anonymous, the identity of the participants shall not be revealed. If you wish to connect to us you can reach us at [email protected] The result of this survey may be used for future research and publication. Thank you for your valuable time, co-operation and understanding to be a part of this survey.

PLEASE answer ALL the queries.

Survey Start Date: April 25, 2020

Survey Lock Date : May 1, 2020

Principal investigator

Dr Muhammed Razmi T, MD, DNB, MNAMS

*Required

1. Sex

Mark only one oval

a. Male

b. Female

c. TransgenderSurvey

2. 2. Age in years *

Mark only one oval

a. 21-30

b. 31-40

c. 41-50

d. 51-60

e. 61-70

f. < 70

3. 3. Profession *

Mark only one oval

a. Doctor directly involved in patient care

b. Doctor/Researcher not directly involved in patient care

4. 4. Highest Degree *

Tick all that apply.

A. MBBS (Bachelor degree)

B. MD/DNB (Master degree)

C. DM/MCh (Superspeciality Degree)

D. PhD or any other research degree2

5. 5. Specialty *

Mark only one oval

A. Dermatology

B. Rheumatology

C. Internal Medicine

D. Infectious Disease

E. Other Specialty

F. Not applicable

6. 6. Number of years since you started to practice? *

Mark only one oval

A. 0-1 year

B. 1-5 years

C. < 5 years

D. Not applicable

7. 7. Country where you practice at present? *



8. 8. Are you dealing with COVID-19 patients/research? *

Mark only one oval

a. Yes

b. No

c. No response

9. 9. Are you interested in COVID-19 related media news/ scientific discussions? *

Mark only one oval

a. Yes

b. No

c. No response

10. 10. Have you prescribed Chloroquine/Hydroxychloroquine before? *

Mark only one oval

a. Yes

b. No

11. 11. In which category of drug that you think Chloroquine/Hydroxychloroquinebelongs to? *

Mark only one oval

A. Antibiotic

B. Antiviral

C. Antimalarial

D. Antihelmenthic

E. No idea

12. 12. Which of the following tests to be done before startingChloroquine/Hydroxychloroquine? *

You can mark multiple options

Tick all that apply.

A. Ophthalmological evaluation

B. Cardiac evaluation

C. Glucose-6-phosphate dehydrogenase (G6PD) assay

D. All of the aboveE. No idea

13. 13. Which of the following are absolute/relative contraindications forhydroxychloroquine? *

You can mark multiple options

Tick all that apply.

A. Pregnancy

B. Retinal vision defects

C. Children

D. None of these

E. No idea

14. 14. Hydroxychloroquine may cause serious cutaneous side effects *

Mark only one oval

A. Yes

B. No

C. No idea

15. 15. Hydroxychloroquine is *

Mark only one oval

A. Immunosuppressant

B. Immunomodulator

C. Immune booster

D. No idea

16. 16. Hydroxychloroquine can cause serious cardiac side effects *

Mark only one oval

A. Always

B. In certain scenarios only

C. Never

D. No idea

17. 17. Ocular toxicity of Hydroxychloroquine develops *

Mark only one oval

A. No ocular toxicity

B. Within days

C. Within months

D. Within a year

E. After >5 years

F. No idea

18. 18. Frequency of ophthalmological evaluation needed in Hydroxychloroquine

Mark only one oval

A. Every 3 months

B. Every year

C. Not needed

D. No idea

E. After 5 years, annually

19. 19. What is your opinion on safety of Hydroxychloroquine ? *

Mark only one oval

A. Relatively safe

B. Relatively unsafe

C. No idea

20. 20. What is your opinion on evidence on its antiviral effects *

Mark only one oval

A. Convinced

B. Not convinced

C. No idea

21. 21. What is your opinion on Hydroxychloroquine use in the COVID-19 clinical trials?*

Mark only one oval

A. Recommends based on its safety and laboratory evidences on its antiviral effects

B. Doubts on its antiviral effects, but can be tried since it is relatively safe

C. Not recommend since it is an unsafe drug, whatever be the evidences on itsantiviral effects

D. Not at all recommending since there is neither evidence for its antiviral effect, nor itis safe

E. No opinion

22. 22. Have you personally taken hydroxychloroquine as a prophylaxis for COVID-19? *

Mark only one oval

A. Yes

B. No

23. 23. What is your opinion on hydroxychloroquine use for prophylaxis of contacts orfrontline health workers? *

Mark only one oval

A. Favour

B. Oppose

C. No idea

24. 24. What is your opinion on hydroxychloroquine use for mass prophylaxis of thegeneral population? *

Mark only one oval

A. Favour

B. Oppose

C. No idea

25. 25. Have you checked Google or other online resources or reference books toanswer this survey? *

Mark only one oval

A. Yes

B. No



 
  References Top

1.
National Taskforce for COVID-19. Advisory on the Use of Hydroxy-Chloroquine as Prophylaxis for SARS-CoV-2 Infection. 2020. Available from: https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinas prophylaxisforSARSCoV2infection.pdf. [Last accessed on 2020 Jun 23].  Back to cited text no. 1
    
2.
CDC Health Alert Network. Severe Illness Associated with Using Non-Pharmaceutical Chloroquine Phosphate to Prevent and Treat Coronavirus Disease 2019 (COVID-19). Available from: https://emergency.cdc.gov/han/2020/han00431.asp. [Last accessed on 2020 Aug 13].  Back to cited text no. 2
    
3.
FDA Cautions Against Use of Hydroxychloroquine or Chloroquine for COVID-19 Outside of the Hospital Setting or a Clinical Trial Due to Risk of Heart Rhythm Problems. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine- or-chloroquine-covid-19-outside-hospital-setting-or.[Last accessed on 2020 May 02].  Back to cited text no. 3
    
4.
Sachdeva M, Shah M, Ziv M, Leshem E, Dodiuk-Gad RP. Risks of hydroxychloroquine use for COVID-19 prophylaxis. J Am Acad Dermatol 2020;83:e73-4.  Back to cited text no. 4
    
5.
Kassi EN, Papavassiliou KA, Papavassiliou AG. G6PD and chloroquine: Selecting the treatment against SARS-CoV-2? J Cell Mol Med 2020;24:4913-4.  Back to cited text no. 5
    
6.
Afra TP, Razmi TM, Bishnoi A, Hafi NB. Hydroxychloroquine use in COVID-19: What is the basis for baseline tests? Lancet Infect Dis 2020;S1473-3099(20)30472-2. doi: 10.1016/S1473-3099(20)30472-2. Online ahead of print.  Back to cited text no. 6
    
7.
Afra TP, Vasudevan Nampoothiri R, Razmi T M. Doubtful precipitation of hemolysis by hydroxychloroquine in glucose-6-phosphate dehydrogenase-deficient patient with COVID-19 infection. Eur J Haematol 2020;5;10.1111/ejh.13460. doi: 10.1111/ejh.13460. Online ahead of print.  Back to cited text no. 7
    
8.
Alia E, Grant-Kels JM. Does hydroxychloroquine combat COVID-19? A timeline of evidence. J Am Acad Dermatol 2020;83:e33-4.  Back to cited text no. 8
    
9.
Singh JA, Saag KG, Bridges SL Jr., Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 2016;68:1-26.  Back to cited text no. 9
    
10.
McGhie TK, Harvey P, Su J, Anderson N, Tomlinson G, Touma Z. Electrocardiogram abnormalities related to anti-malarials in systemic lupus erythematosus. Clin Exp Rheumatol 2018;36:545-51.  Back to cited text no. 10
    
11.
Liu D, Li X, Zhang Y, Kwong JS, Li L, Zhang Y, et al. Chloroquine and hydroxychloroquine are associated with reduced cardiovascular risk: A systematic review and meta-analysis. Drug Des Devel Ther 2018;12:1685-95.  Back to cited text no. 11
    
12.
Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent guidance for navigating and circumventing the QTc-prolonging and torsadogenic potential of possible pharmacotherapies for coronavirus disease 19 (COVID-19). Mayo Clin Proc 2020;95:1213-21.  Back to cited text no. 12
    
13.
Haeusler IL, Chan XH, Guérin PJ, White NJ. The arrhythmogenic cardiotoxicity of the quinoline and structurally related antimalarial drugs: A systematic review. BMC Med 2018;16:200.  Back to cited text no. 13
    
14.
Saleh M, Gabriels J, Chang D, Kim BS, Mansoor A, Mahmood E, et al. The effect of chloroquine, hydroxychloroquine and azithromycin on the corrected QT interval in patients with SARS-CoV-2 infection. Circ Arrhythm Electrophysiol 2020;13:e008662.  Back to cited text no. 14
    
15.
Mehra MR, Ruschitzka F, Patel AN. Retraction: “Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: A multinational registry analysis”. Lancet 2020;395:1820.  Back to cited text no. 15
    
16.
Mohammad S, Clowse ME, Eudy AM, Criscione-Schreiber LG. Examination of hydroxychloroquine use and hemolytic anemia in G6PDH-deficient patients. Arthritis Care Res (Hoboken) 2018;70:481-5.  Back to cited text no. 16
    
17.
Commons RJ, Simpson JA, Thriemer K, Chu CS, Douglas NM, Abreha T, et al. The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: A WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis. BMC Med 2019;17:151.  Back to cited text no. 17
    
18.
Beauverd Y, Adam Y, Assouline B, Samii K. COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency. Eur J Haematol 2020;105:357-9.  Back to cited text no. 18
    
19.
Ponticelli C, Moroni G. Hydroxychloroquine in systemic lupus erythematosus (SLE). Expert Opin Drug Saf 2017;16:411-9.  Back to cited text no. 19
    



 
 
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