The irrational and incompliance use of antibiotics has been correlated to bacterial resistance. Several methods evaluated patients' compliance with oral antibiotics have been conducted. However, a standard questionnaire for evaluating oral antibiotics compliance in Indonesian has not been developed yet. This study was conducted to record the content validity of the developed questionnaire called 20-KAO to assess compliance with oral antibiotics. The validity content test was conducted through six experts review using the Item Content Validity Index (I-CVI) and Scale-Content Validity Index (S-CVI). The experts were also requested to provide recommendations for each item, whether revisions or deletion. After the review process, the number of questions remains unchanged. A total of 19 out of 20 items had an I-CVI of 1.00, and S-CVI was calculated at 0.98. Therefore, 20 items of the 20-KAO questionnaire have excellent content validity. However, future construct validity and reliability test to analyze the responses of targeted respondents and the questionnaire's consistency are needed.

Antibiotics arechemical substances produced by microorganisms that can inhibit or killbacteria (Fair &Tor, 2014).Antibiotics usage for an infection in the low and middle-income countries hasincreased up to 65% from 2010-2015 (Klein et al., 2018). An increase hasfollowed the increase in usage in bacterial resistance. The irrational use ofantibiotics, such as treating viral infections and usage on the farm andfisheries, correlates with bacterial resistance (Economou & Gousia, 2015). Furthermore, thepatient's compliance in taking their oral antibiotics also contributed tobacterial resistance prevalence (Moradi et al., 2013).

Several studiesevaluated the patient's compliance with oral antibiotics have been conductedusing various methods. Measuring compliance using objective or subjectivemethods has its particular limitations (Jin et al., 2008). Examples ofobjective methods in assessing patient compliance are pill count and MedicationEvent Monitoring System (MEMS). Pill count is a physical count of the number ofpills that remain and compares to the prescription's instruction (Lam & Fresco, 2015). The MEMS is amedication container contains a microelectronic chip that records the date andtime of opening of every bottle (Llor et al., 2013). Although MEMSmeasures compliance accurately, it cannot be used in an everyday situation.Besides, pill count cannot describe specifically the aspects of compliance,such as timing, dosing, and taking compliance (Willams et al., 2013). Hence, a subjective method such as using aquestionnaire is preferable because of less cost, non-judgmental,non-threatening, quick, and comfortable in collecting results (Lam & Fresco, 2015; Llor et al., 2013; Ponto, 2015).

Variousquestionnaires such as Medication Adherence Questionnaire (MAQ), MedicationAdherence Rating Scale (MARS), Patient Medication Adherence Questionnaire(PMAQ), Morisky Medication Adherence Scale (MMAS), etc. have been developed andvalidated to measure compliance (Morisky et al., 1986; Thompson et al., 2000; Duong et al., 2001). However, thequestionnaires have not been translated and validated into Bahasa Indonesia for measuring compliance with oral antibioticstreatment in Indonesia. A study has been conducted to validate the Englishversion of Morisky 3, 4, and 5-item questionnaires in assessing oralantibiotics compliance (Treibich & Ventelou, 2017).

In Indonesia,measuring oral antibiotics compliance usually uses pill count. Therefore, therehas been no questionnaire developed yet. Hence, developing a standardquestionnaire for evaluating oral antibiotics compliance in Bahasa Indonesia is essentials. Indeveloping a questionnaire, validity tests are needed in order to evaluatewhether it measures what it is supposed to measure or not (Setia, 2017). Validity testsare classified into two broad categories, viz internal and external validity (Bolarinwa, 2015). Internal validityincludes content validity that measures the degree to which the instrumentcomprehensively assesses the construct of interest usually conducted beforeexternal validity. Therefore, this study was conducted to record the developedquestionnaire's content validity assessing compliance with oral antibiotics.

This study was conducted observationallyfrom August to September 2020 to establish the evidence of content validity ofthe developed questionnaire, namely 20-KAO from experts.

The 20-KAO questionnaire wasdeveloped in Bahasa Indonesia andaimed to assess short-course oral antibiotics usage compliance. The name 20-KAOwas developed from 20 items in assessing compliance with oral antibiotics or inBahasa Indonesia: Kepatuhan Antibiotik Oral (KAO). Thequestionnaire was developed in four sections and contained 20 questions.Section one contained ten questions to evaluate whether the patients understoodthe dosage regimens and took their dosage correctly or not and the reasonsbehind their action in taking the dosage. Section two rated the patient'sunderstanding, compliance, and the reasons in how many times they took thedosage daily through five questions. In the third section, it was assessed howpatients gave an interval between their dosages and the reasons why they didit. In the last section, the patient's understanding of the duration of takingthe antibiotics, and whether they had stopped taking the antibiotics before itshould be stopped, and their reasons to do so. Additionally, patients were alsoasked to fill in the number of pills left in the questionnaire and if they usedother non-prescribed medication.

The literatureshows that the ideal number of content experts needed in a validation study isstill controversial. However, the suggestions are between three and ten experts(Polit & Beck, 2006). In this study, a total of sixexperts were selected. Three of them were academic experts, while threeremained were registered pharmacists. These experts’ proportion were designedintentionally so that the review results would reflect academic and practicalopinions. The academic experts were selected based on their experiences indeveloping a questionnaire and the pharmacists' experts' experiences in givingpatient consultation to improve the patient's compliance. The experts wereinvited from educational institutions and community health centers in Surabaya(they were registered pharmacists in Wonokromo, Gayungan, and KalirungkutCommunity Health Centers and academic lecturers in clinical as well ascommunity pharmacy at Universitas Airlangga and Akademi Farmasi Surabaya).After getting their approval, the researcher sent an informed consent form, aninformation cover letter, and the questionnaire attached to the evaluationcriteria. The evaluation form contained an explanation of the validationprocedure. The experts were asked to assess the relevance of each question inthe questionnaire.

The relevancemeant whether all the items in the 20-KAO questionnaire referred to measure theantibiotics usage compliance in dose, frequency, and the duration of therapy.To determine the relevance of each item, a four scale was used (1 = notrelevant, 2 = somewhat relevant, 3 = quite relevant, 4 = highly relevant). Theexperts were also requested to provide recommendations for each item, eitherrevisions or deletion. The maximum time for validating the questionnaire foreach expert was two weeks, and they were requested to return the result throughemail or in-person to the researcher. The response from the experts wasanalyzed through Content Validity Index (CVI), specifically Item ContentValidity Index (I-CVI) and Scale-Content Validity Index (S-CVI). The I-CVI wascalculated in every item from the number of experts giving 3 or 4 scoresdivided by the total number of experts, while S-CVI was computed as the averageof I-CVI from all the items. The questionnaire would qualify to be contentvalid if the S-CVI greater than 0.90.

All of the six experts invited wereagreed to participate. They were registered pharmacists in Wonokromo, Gayungan,and Kalirungkut Community Health Centers and academic lecturers in clinical andcommunity pharmacy at Universitas Airlangga and Akademi Farmasi Surabaya. Allexperts are deliberately selected from Surabaya to facilitate communication.The mean age of the experts was 41.5 (SD=9.16) years. After the validationprocess, the number of question items in the 20-KAO questionnaire remainedunchanged. There were 19 out of 20 items that had an I-CVI of 1.00. Therefore,S-CVI was calculated at 0.98 as shown in Table I.

Table I. Result for the contentvalidation of 20-KAO questionnaire

aNumber of items that achieved the I-CVI of 1.00 divided by the totalnumber of items to be validated in the questionnaire

Table I showed that the questionnaire hadexcellent content validity in measuring oral antibiotic compliance. However,the experts gave some editorial revisions to make the sentences morecomfortable to be understood, as presented in Table II.

Table II. Editorialrevision of 20-KAO questionnaire

Among the 20 items validated, the only item with I-CVI less than 1.00and significant editorial revision was Q11. The Q11 was developed to assesswhether the patients understand how many times they should take theirantibiotics or not. Two of the six experts suggested changing the sentencestructured because the original sentence was too complicated. Changes in thestructure of the questions were then carried out after consultation with theseexperts. The final form of the 20-KAO questionnaire after the content validityprocess was shown in Table III.

Table III. The 20-KAO questionnaire

To our knowledge, there had no reported studies developing aquestionnaire that evaluated oral antibiotics compliance in Indonesia. A studyin Lithuania by Kandrotaite et al. (2013) developed a 91-items questionnaire adapted fromASK-20, SF-12, and Morisky scale questionnaire to identify the risk ofnonadherence antibiotics treatments. It was said that the developedquestionnaire covered the identification of the five-dimension adherence modeldeveloped by World Health Organization (Kandrotaite et al.,2013). However,although the developed questionnaire had been discussed with nineprofessionals, it had not been validated yet. Besides, one of the studies inIndonesia that used questionnaires to measure antibiotics compliance was thestudy by Muljabar and Supadmi (2014) that used 8-items MMAS. However,the study did not validate the questionnaire directly to patients receivingantibiotics. Therefore, the questionnaire developed in this study could betested for construct validity and reliability tests.

Construct validity is the degree to which an instrument measures thetrait or theoretical construct intended to measure, while reliability test isthe extent to which a questionnaire produces consistent results on repeatedtrials (Boateng et al., 2018; Kimberlin & Winterstein,2008). Constructvalidity for the 20-KAO questionnaire is essentials to measure how well thetargeted respondents give answers as the questionnaire aims to measure, whilethe reliability test is useful to assess whether the questionnaire will giveconsistency in results. Future construct validity and reliability test for20-KAO questionnaire can be done through distribution to the patient'sprescribed antibiotics and then analyze their responses.

The 20-KAO questionnaire was found to have excellentcontent validity based on six experts' reviews. Future construct validity andreliability tests for 20-KAO are needed to be conducted to analyze the respondof targeted respondents and the consistency of the questionnaire.

The authors would like to thank The Ministry ofEducation and Culture Republic of Indonesia for the funding support in the schemeof Penelitian Dosen Pemula 2020, the community health centers of Surabaya forthe permission, the experts who participated in this study, also AkademiFarmasi Surabaya for the approvals.

Boateng,G.O., Neilandsm T.B., Fongillo, E.A., Melgar-Quiñonez, H.R., & Young, S.L.(2018). Best Practices for Developing and Validating Scales for Health, Social,and Behavioral Research: A Primer. Frontiersin Public Health, 6, 149. doi:10.3389/fpubh.2018.00149

Bolarinwa,O.A. (2015). Principles and methods of validity and reliability testing ofquestionnaires used in social and health science researches. Nigerian Postgraduate Medical Journal, 22(4), 195-201. doi:10.4103/1117-1936.173959

Duong, M.,Piroth, L., Grappin, M., Forte, F., Peytavin, G., Buisson, M., Chavanet, P.,& Portier, H. (2001). Evaluation of the Patient Medication AdherenceQuestionnaire as a tool for self-reported adherence assessment in HIV-infectedpatients on antiretroviral regimens. HIVClinical Trials, 2(2), 128-135.doi:10.1310/M3JR-G390-LXCM-F62G

Economou, V.& Gousia, P. (2015). Agriculture and food animals as a source of antimicrobial-resistantbacteria. Infection and Drug Resistance,8, 49-61. doi:10.2147/IDR.S55778

Fair, R.J. & Tor, Y. (2014). Antibiotics andBacterial Resistance in the 21st Century. Perspectivein Medicinal Chemistry, 6, 25-64.doi:10.4137/PMC.S14459

Jin, J.,Sklar, G.E., Oh, V.M.S., & Li, S.C. (2008). Factors affecting therapeuticcompliance: A review from the patient’s perspective. Therapeutics and Clinical Risk Management, 4(1), 269-286. doi:10.2147/tcrm.s1458

Kandrotaite,K., Smigelskas, K., Janusauskiene, D., Jievaltas, M., Maciulaitis, R., & Briedis,V. (2013). Development of a short questionnaire to identify the risk ofnonadherence to antibiotic treatment. CurrentMedical Research and Opinion, 29(11),1555-1563. doi:10.1185/03007995.2013.835255

Kimberlin,C.L. & Winterstein, A.G. (2008). Validity and reliability of measurementinstruments used in research. AmericanJournal of Health-System Pharmacy, 65(23),2276-2284. doi:10.2146/ajhp070364

Klein, E.Y.,Boeckel, T.P.V., Martinez, E.M., Pant, S., Gandra, S., Levin, S.A., Goossens,H., & Laxminarayan, R. (2018). Global increase and geographic convergencein antibiotic consumption between 2000 and 2015. Proceedings of the National Academy of Sciences of the United States ofAmerica, 115(15), E3463-E3470.doi:10.1073/pnas.1717295115

Lam, W.Y.& Fresco, O. (2015). Medication Adherence Measures: An Overview. BioMed Research International, 2015, 217047. doi:10.1155/2015/217047

Llor, C., Hernández,S., Bayona, C., Moragas, A., Sierra, N., Hernández, M., & Miravitlles, M.(2013). A study of adherence to antibiotic treatment in ambulatory respiratoryinfections. International Journal ofInfectious Diseases, 17(3),e168-172. doi:10.1016/j.ijid.2012.09.012

Martinez,J.L. (2017). Effect of antibiotics on bacterial populations: amulti-hierachical selection process. F1000Research,6, 51. doi:10.12688/f1000research.9685.1

Moradi, M.,Hamedi-Shahraki, S., Rezayee, M., & Verdi, M. (2013). Compliance withantimicrobial therapy: Evaluating the related factors. Journal of Pharmaceutical Care, 1(2),60-64.

Morisky,D.E., Green, L.W., & Levine, D.M. (1986). Concurrent and predictivevalidity of a self-reported measure of medication adherence. Medical Care, 24(1), 67-74. doi:10.1097/00005650-198601000-00007

Muljabar,S.M. & Supadmi, W. (2014). Pengaruh Pemberian Informasi Obat terhadapTingkat Kepatuhan Penggunaan Antibiotika pada Pasien ISPA di Puskesmas KotagedeI Yogyakarta. Pharmaciana: JurnalKefarmasian, 4(2), 143-149. doi:10.12928/pharmaciana.v4i2.1571

Polit, D.F.& Beck, C.T. (2006). The content validity index: are you sure you know what'sbeing reported? Critique and recommendations. Research in Nursing and Health, 29(5),489-497. doi:10.1002/nur.20147

Ponto, J.(2015). Understanding and Evaluating Survey Research. Journal of the Advanced Practitioner in Oncology, 6(2), 168-171.

Setia, M.S.(2017). Methodology Series Module 9: Designing Questionnaires and ClinicalRecord Forms – Part II. Indian Journal ofDermatology, 62(3), 258-261. doi:10.4103/ijd.IJD_200_17

Thompson,K., Kulkarni, J., & Sergejew, A.A. (2000). Reliability and validity of anew Medication Adherence Rating Scale (MARS) for the psychoses. Schizophrenia Research, 42(3), 241-247. doi:10.1016/s0920-9964(99)00130-9

Treibich, C.& Ventelou, B. (2017). Validation of a short-form questionnaire to checkpatients' adherence to antibiotic treatments in an outpatient setting. European Journal of Public Health, 27(6), 978-980. doi:10.1093/eurpub/ckx146

Williams,A.B., Amico, K.R., Bova, C., & Womack, J.A. (2013). A proposal for qualitystandards for measuring medication adherence in research. AIDS and Behavior, 17(1),284-297. doi:10.1007/s10461-012-0172-7