Development of a Tool for Assessing Patient Compliance on Various Ayurvedic Formulations used for Internal Administration

Introduction: Compliance is a process where the patient follows the prescribed and dispensed regimen as intended by the prescriber. Poor compliance has been reported as it is the most common cause of non-response to medication. There is no single best indicator to assess patient compliance in Health Research. This study aims to develop and validate a new questionnaire considering the pharmaceutical properties of Ayurvedic medicines to measure patient compliance. Methods: The first phase consisted of a qualitative phase to identify the variables to measure patient compliance through in-depth interviews among five doctors and focus group discussion with eight practitioners, and pre-test with respondents, experts, and peers. The second phase was a quantitative phase to assess the respective responses of patients towards the questionnaire through a cross-sectional survey among 106 subjects as a pilot study. Original Research Article Sumi et al.; JPRI, 33(51B): 11-22, 2021; Article no.JPRI.77256 12 Results: The qualitative analysis reported variables that were seen spread across eight domains were used to measure compliance. Conclusion: Ayurvedic treatment is personalized and there is always a scope for a remake of formulation designing for each individual. Sticking on to appropriate prescriptions after properly assessing the needs of the patient and the reason for their non-compliance can bring a revolution in terms of cost-effectiveness and time. The wastage of medicines, whether raw drugs or processed ones can be prevented by recognizing the factors for non-compliance. There is always a scope for improvement with further alike or more developed research in patient compliance in Ayurveda.


INTRODUCTION
Patient compliance consists of a complex and multidimensional health issue globally. To explore the perceptions and acceptance of Ayurvedic medicines, particular tools are not available. Patients' acceptance is otherwise patients' satisfaction. Compliance is defined in several ways. The interpretation of the term depends on the philosophical context during which the concept is settled [1]. Compliance is a process where the patient follows the prescribed and dispensed regimen as intended by the prescriber and dispenser [2]. Poor compliance has been reported as it is the most common cause of non-response to medication [3]. Unit evidence shows that patients who adhere to recommendations have better health outcomes than people who do not adhere.
It has been observed from previous studies that several components are involved in patient compliance. Compliance, the oldest term to explain medication-taking behaviour seems to suggest a single-sided interaction where the clinician decides on the appropriate treatment, which the patient has to adjust to no matter its suitability. The terms compliance, adherence, and concordance are often used interchangeably in research and clinical practice [2]. Even though related, they do possess slight differences. WHO states that non-adherence to medication may be a "Worldwide problem of striking magnitude" [4]. WHO also defines adherence as "the extent to which the person's behaviour (including medication taking) corresponds with agreed recommendations from a healthcare provider [5]. WHO in a trial to cut back the paternalistic nature of the term 'compliance', introduced the term 'adherence' [1]. According to WHO, various factors are leading to medication adherence, which are normally classified into 5 categories [6].

1) Socio-economic factors 2) Patient-related factors 3) Therapy-related factors 4) Condition related factors 5) Health-care team-related factors
The factors associated with a characteristic of the disease, patient's socio-economic factors, poor efficiency, medication side effects, duration of treatment, the severity of the disease, long period medication are the determinants of patient compliance [2].
Demographic and disease factors have generally been found to be pure indicators of compliance. The patient's relationship to parents or relatives and participation of spouse in treatment enhances compliance [3].
The duration of therapy could be a factor that may influence the extent of compliance. Compliance with short-term medications is usually considered to be somewhat more than that for long-term medication regimens. The typical rate of compliance tends to converge to 50% for long-term therapy, no matter disease, and compliance behavior tends to lessen with time [7]. The increasing prevalence of 3 chronic conditions where long-term therapy is prescribed suggests that compliance will still be a region of concern.
The long duration of treatment, a high number, and the high cost of medication are found to be negatively influencing compliance and the fear of the adverse effect of the medication is additionally a reason for non-compliance [8]. Unfortunately, all these factors are heavily contributing towards the non-compliance in the case of Ayurvedic medications. Still, no study has been conducted towards the assessment and improvement of patient compliance with Ayurvedic medicines due to the lack of tools available.
Compliance is measured directly and indirectly. Direct measurements of compliance usually involve the detection of a chemical in a very bodily fluid [1]. Indirect measurement of compliance includes therapeutic or preventive outcome, the impression of the physician or predictability, patient interview, prescription filling dates, and pill counts [9].
'Concordance' suggests that patients should take more responsibility even if no one is willing to try this [1]. The term 'concordance' doesn't take under consideration the cases where some patients refuse treatment either because they are unaware of the cost and benefits or likely to be hurt [10]. Methods of measuring adherence can be classified as direct method and indirect method. Direct methods include directly observed therapy, measurement of drug concentration in blood, and measurement of the biological marker within the body [4]. Indirect methods [11] include • Patient self-report or questionnaire is one of the important indirect methods of measuring medication adherence and persistence and it is the foremost commonly used method within the clinical setting. • Pill counts • Pharmacy fill data • Electronic medication monitoring • Assessment of the patient's clinical response Some interventions can be done to boost patient compliance.
• Educational strategies like verbal communication or counselling are shown to boost compliance [12 ]. Written information is also effective for shortterm medication therapy [13].
• 'Behavioural strategies like reminders and special medication containers are shown to boost compliance [14]. • Compliance can best be improved to a great extent by interventions combining educational and behavioural components [15].

Morisky Medication Adherence Scale (MMAS):
A adherence scale for medicament should be able to accurately capture the beliefs, barriers, and behaviour associated with medication adherence. It should even be easy to administer, understand, and be precise [16]. In 1986, Dr. Morisky and his colleagues published this instrument. The primary Morisky scale has four items that have dichotomous response categories with yes or no [17]. In 2008, a modified eight-item Morisky Medication Adherence Scale(MMAS-8) was developed from the first four-item Morisky scale [18]. The primary 4 seven items were dichotomous response categories with yes or no and also the last item was a five-point Likert response. MMAS-4 and MMAS-8 are designed to explain the medicationtaking behaviour of patients but they appear to be ineffective in comprehensively assessing the reasons or predictors of medication adherence.
They are good estimates of the medicationtaking behavior, and good screening and monitoring tools to spot those patients who might possess medication adherence problems. These scales help to recognize and monitor high-risk non-adherent patients. But they are not good explanatory tools for inferring why patients are not adherent, which can cause a poor relationship between the Morisky scale and objective clinical outcome measures [4]. In a study, it had been found that blood glucose levels were not related to Morisky  The patient's perspective on medication taking, which may be a key component of compliance/adherence behaviours, was neglected by researchers for a long time [7]. However since the 1990s this area has been focused on and suggested that patients' view on medication plays a key role in determining compliance/adherence. In modern medicine, the extent of non-adherence in asthma/COPD, cardiovascular diseases, and other diseases are usually studied.
Ayurveda pharmaceutics or Bhaishajya Kalpana deals with a variety of dosage forms including primary and secondary dosage forms having different therapeutic utility. The distaste of drugs and their large dose are the chief factors that influence the compliance of patients towards Ayurvedic drugs. In the present era in which Ayurveda is gaining global recognition, these factors should be tackled well to achieve acceptance for Ayurvedic medicines. Nowadays, there is a wide choice for treatment and to ensure the global acceptance of Ayurveda more people should opt for Ayurveda too. This is possible only by identifying the reasons or explanations behind denying Ayurveda and further steps can be taken to rectify them accordingly.
To better understand medication-taking behaviour, researchers need to examine the patients' perspectives. Till now, there is no gold standard method to estimate the medicationtaking behaviour of patients [4].
Non-compliance to Ayurvedic medication used for internal administration is commonly observed. Hence to explore new strategies to enhance better compliance and better clinical outcome without compromising the fundamental concept of Ayurveda, this study was conducted. The truth is that many patients experience difficulty with medication-taking resulting in suboptimal adherence. As health-care professionals, we have a vital role in combating this problem and hence an attempt was made to develop a tool for assessing patient compliance on Ayurvedic medicines used for internal administration. The present era demands the development and validation of a scale for measurements following Ayurvedic concepts. The various factors leading to non-compliance in an individual are important and should be identified before establishing practical ways of developing a concept to increase compliance rates.
A unique combination of the padachatushtayas mentioned in Ayurveda with its prescribed qualities is of utmost importance. Among Chatushtayas, the vaidya stands supreme because of possessing true knowledge by which he selects the drugs for patients based on his Prakriti, Desa, etc. In many aspects, Ayurveda focuses on personalized medicine, the role of patients in the global acceptance of Ayurveda is never too low. The suggestions and modifications should come from their experiences and knowledge as well. This study is designed with the objectives to develop a valid and reliable tool for assessing patient compliance and to trace out the problems faced by patients while taking Ayurvedic medicines.

METHODOLOGY
The mixed method study was conducted in sequential exploratory design [22]. (Fig. 1)

Objectives
• Primary objectives: To develop a valid and reliable tool for assessing patient compliance. • Secondary objectives: To trace out the problems faced by patients while taking Ayurvedic medicines.

Conceptualization
Detailed literary research was carried out to derive the concept of patient compliance. Experts from the fields of Ayurveda were interviewed for the collection of items and 15 items were selected. Each item was reviewed to correspond with the literary hints. Along with this, a focus group discussion was convened.

Operationalization of the construct patient compliance
Compliance can be defined in various ways. The interpretation of the term depends on the philosophical context in which the concept is settled.

Item Generation
Items in the tool were generated based on the review of relevant literature, in-depth interview with experts, getting respondents' opinions, and focus group discussion with experts. These processes ensured the inclusion of various dimensions of concept and appropriate items under specific domains.

Collecting items from experts
Experts from the fields of Ayurveda were interviewed for the collection of items. A set of items already framed was discussed and each item was reviewed to correspond with the literary hints. Along with this, a focus group discussion was convened.

Focus group discussion (FGD)
Focus group discussion was conducted in order to get the perceptions, opinions and attitudes regarding compliance (Fig. 2).

Selection of subjects in FGD
Individuals chosen for FGD were familiar with the subject and were known for their ability to respectfully share their opinions, and were willing to volunteer for about 2 hours.

Contacting and informing participants
The initial contact of participants was done by mail, telephone, and in person. On the previous day, the participants were all contacted personally by the investigator and their presence was ensured. The facilitator was the investigator herself. The discussion was led by a moderator (investigator) assisted by an observer who took notes and did arrangements. Participants' opinion about the topic was asked. It was ensured that they felt comfortable while sharing their opinion. Participant size was decided as 8. The topic of discussion was based on the components involved in patient compliance. The drug-related factors influencing compliance were highlighted. Determinants of non-compliance related to pharmaceutical aspects of the drug were mainly considered.
Fixing the variables: Pharmaceutical dosage forms, palatability of different dosage forms, frequency of medicine intake, poly-pharmacy, availability of medicines, medication cost, severity of illness, duration of treatment, fear of medicine interaction with allopathic medications, poor efficacy of medicines, time of administration, colour of medicines, particular odour of certain dosage forms, doctor-patient relationship, pathya-apathyas were discussed.
Item selection: The items were again discussed by experts in detail and once again they were checked whether to keep or discard. From 15 items, 8 items were selected (Fig. 3).

Formatting the questionnaire
Data analysis was done at three levels: open, axial and selective coding. Open coding was a line-by-line scrutiny of the data, to identify the codes expressed by the participants. Fifteen quotes related to compliance emerged from the data. Labelled the related quotes and grouped them into categories in axial coding. The next step was to identify a core category, which related to all other categories at the selective coding stage.
All the codes were taken as variables. These variables were converted into questions. Selected simple wording for each question to ensure the acquiescence of the questionnaire.

Item Wording, Sequencing and Formatting
Selected items were worded appropriately to suit the level of comprehension of the respondent population of patients using Ayurveda medicines and sequenced from general to specific. Discussions on the structure of questions and responses were made and questions were analysed.

Cognitive piloting
Cognitive piloting was done for identifying problems with question wording comprehension and recall and for ensuring that items are capturing the underlying construct.

Scoring Pattern
Giving equal weightage to all items, scoring was done.

Translation and Back Translation
Items were translated into the local language Malayalam. Items were translated back to English by 2 linguistic experts. It was particularly made sure that the meaning was not altered in translation.

Pre-test
Here, before a full-scale study, a questionnaire is tested on a statistically small sample of respondents in order to identify problems related to wordings.
The method followed for pre-test are as follows:

3.6.1Expert review
The items were reviewed by experts to comment on format, clarity, and to ensure content coverage and simplicity of items in the tool.

Peer review
The translated tool was given to peers.

Respondent's review
Questionnaires were administered to the respondent population to test the wording and comprehensibility.

Pilot Study
For the pilot study, 106 individuals were randomly selected. The comprehensibility of the questionnaire and the anticipated logistic issues that can occur during the final administration of the questionnaire were tested.
Description of the questionnaire: Selfadministered questionnaire was developed in the official language of Kerala (Malayalam). Response to the questionnaire was made in a mixed format. It included dichotomous questions, multiple-choice questions and open-end questions.
The online semi-structured questionnaire was developed in Google forms. The link of the questionnaire was sent through emails, WhatsApp and other social media to the contacts of the investigator and the survey was conducted. The process of the questionnaire development and its piloting is being represented as a flow chart (Fig. 4).

Analysis of the Survey
Out of 106 responses, about 53.8 % of participants mentioned that the taste of medicines affected the consumption of medicine. ( Figure 5) Among them, 64.4% of participants showed hatred towards medicines with bitter taste, 62.7 % towards astringent, 8.5% towards pungent, 5.1% towards sour and 1.7% towards sweet taste. No aversion was mentioned for the medicines with salt taste. 39.6% of the participants mentioned that the taste did not affect the consumption of medicine. 6.6% of participants were not sure about the question.
About 54.7% of participants mentioned that the form of medicine affects their medicine consumption. Among them, 36.7% showed dislike towards medicines in the form of ghee, 35% towards Kashaya, 25% towards oil, 23.3% towards Churna, 3.3% towards Arista, asava and tablets and 1.7% towards Lehya form of medicine. 35.8 % responded that the different forms of medicine did not affect the consumption of medicine. 9.4 % were not sure about the question (Fig. 6). 71.7% of participants mentioned that the increased dose of Ayurvedic medicines did not influence the usage. But about 19.8% showed dislike towards the increased dosage. 8.5% of participants were not sure about the question.
In 57.5% of participants, the increased expense of Ayurvedic medicines did not adversely affect the medicine intake. But in 33% of participants it was adversely affected. Repeated dosage of Ayurvedic medicine hinders the medicine usage in 39.6% of participants, but not affected in 50%. Consumption of more than one medicine in the prescription did not affect 59.4% of participants but it adversely affected 31.1%.
About 34% of participants were possessing fear towards the side effects of Ayurvedic medicines. When asked about the reasons behind this response, various responses include fear of heavy metal content, lack of proper testing of drugs, drug interactions when used along with allopathic medications and the presence of preservatives.
Delayed response of Ayurvedic medicine was mentioned by 43.4% of participants. While 41.5% believe that delayed response does not influence the consumption of Ayurvedic medicines. (Fig. 7). 57 members tried to obey more than 80% of advice from doctors regarding intake of medicine, 34 responses showed following 60 to 80%, 8 responses towards 40-60% and 7 responses showed following below 40% of doctor's advice. (Fig. 8). physician's discomfort to be ready with fresh drugs always, as all drugs are not available at all places and seasons. Moreover, the bitter and pungent taste, large dose, longer duration taken for efficacy to come to play etc. also stand as demerits. It is high time to think about alternatives in patient-compliant forms without sacrificing much in their efficacy.

DISCUSSION
The major processes involved in the modification of the primary dosage forms include drying of the raw drug, heating of the formulation and thereby making it into thicker consistency, addition of sweetening agents, fermentation, packing and containers used in storage or preservation. Since the main aim of modification is to retain the therapeutic efficacy of the dosage form, improved shelf life and increased palatability the various further processes are carried out. By heating, the moisture content if any present in the formulation or in the raw drug is removed, thereby preventing susceptibility to microbial attack. Considering all these factors, selecting more patient-friendly medications can increase the adherence and acceptance of patients towards Ayurvedic medications. Using this tool, the involvement of factors contributing to decrease in patient compliance can be identified and corrective measures can be taken accordingly.

CONCLUSION
The questionnaire filled by the participants after filing their consent is a data generation based on their own unbiased opinion. But they don't give the causes for their opinion or for the hatred towards some particular medicines. This might be attributed to the lack of awareness of pure Ayurveda in the society. Sometimes a family with an older generation only has an inclination towards Ayurveda. In Ayurveda, different varieties of formulations are available. There is always a scope for remake or formulation designing with respect to each individual. The wastage of medicines can be prevented whether raw drugs or the processed ones by recognizing the factors for non-compliance. This way, the acceptability and promotion of Ayurvedic science can be sought. There is always a scope for improvement with further alike or more developed research in patient compliance in Ayurveda.

LIMITATIONS
The pre-test was done in a single hospital.
The survey could be conducted as online only which prevented data collection from ground zero level.
Exploratory factor analysis was not done. Hence, it is not sure whether the theoretical constructs match with those obtained on data analysis. So, a readily usable patient compliance tool, which can be applied in a clinician's table top was not developed.

RECOMMENDATIONS
Study can be done in patients of different areas and then only results can be generalized.
To determine the magnitude of the problem faced by patients, FGD can be done in patients suffering from different diseases.

CONSENT
As per international standard or university standard, respondents' written consent has been collected and preserved by the author(s).