Effects of prescription drug diversion, misuse and abuse on the health system in eThekwini District, KwaZulu-Natal, South Africa: Key stakeholders’ perceptions CURRENT STATUS: POSTED

Background: Prescription drug diversion, misuse and abuse is a growing health threat negatively impacting the health care system and individuals globally. Most research has been conducted in high-income-countries. Little is known about prescription drug diversion, misuse and abuse to support anecdotal reports in resource-limited settings. Purpose: The main objective of this study is to determine prescription drug diversion, misuse and abuse practices in eThekwini district from the perspective of the health care providers, law enforcement, pharmacists, drug users and people living with HIV. Methods: Semi-structured in-depth-interviews were conducted between June-December 2018 among key stakeholders who were purposively sampled in eThekwini district. Thematic analysis was used to identify emergent themes around practices of prescription drug diversion, misuse and abuse. Results: Five main themes emerged during the interviews: manifestation of drug diversion; consumer’s attitude and behaviour; availability of medicines; gaps in the health care system; and lastly challenges and barriers to drug abuse treatment. Accidental addiction, health system gaps and consumer’s attitude and behaviours were perceived as significant contributing factors to the problem therefore negatively impacting health care providers and consumers. Conclusion: The study highlights the emerging practices of prescription drug diversion, misuse and abuse as a serious growing problem occurring through legal and illegal channels to anyone since the addictive medicines are readily available and easily accessible. We recommend a collaborative approach to address prescription drug diversion since the prescriber, dispenser, consumer and law enforcement are involved in the cycle to drug usage. in-depth data collection. We this study conducted 2018. We recruited key stakeholders of prescription drug diversion, misuse and abuse in eThekwini district. We defined key stakeholders of prescription drug diversion, misuse and abuse as parties involved in medicine distribution and usage. Through the interviews, data was collected on and practice of prescription drug diversion, misuse and abuse. We used face-to-face, in-depth interviews as they can reveal new information, uncover hidden practices and provide insight into the topic, (38) which is imperative in understanding the perceived practices.


Introduction
The United Nations Office of Drugs and Crimes noted analgesics, tranquilizers, stimulants and antibiotics as the commonly misused medicines worldwide (1). Despite that pharmaceuticals play a significant role in healthcare, many recreational drugs were once used or prescribed by medical professionals and later prohibited due to their adverse consequences that could no longer be ignored (2)(3)(4). The diversion, misuse and abuse of pharmaceutical products is a growing health threat negatively impacting the health system, individuals, morbidity and mortality rates (1,(5)(6)(7). Globally, the consumption of recreational drugs such as heroin and cocaine appeared stable whilst the consumption of synthetic and prescription drugs is increasing influenced by their widespread availability, affordability and perceived safety (1,8,9). The estimates for misuse of medicines either obtained over-the-counter and/or by prescription is driven by the prescribing patterns and the retail nature of pharmacies (8). Globally, about 190 000 drug-related deaths were attributed to misuse of prescription drugs in 2015 (10). Opioid use disorder and its consequences are serious public health problems (11). Individuals with behavioural practices of opioids misuse may develop dependency, opioid use disorder and sometimes transition to heroin use. Subsequently leading to the increase incidence rates of blood-borne infections such as human immunodeficiency virus (HIV), hepatitis B and C which are prevalent among key populations including injecting drug users (12,13). Worldwide, HIV and opioid use disorder manifest as intersecting epidemics (14). Therefore, hindering the global priority to control the HIV epidemic especially among key populations (15). In South Africa there is limited data on drug diversion, misuse and abuse. The misuse of opioids in the form of codeine containing products has recently being documented as most commonly accessed in local pharmacies (5,(16)(17)(18)(19)(20)(21)(22). Tolerance, dependence and addiction of codeine can develop very rapidly (11). Whilst, about 80% of medical professionals lack appropriate knowledge or guidance on prescribing potentially addictive medicines (16). In addition to the stigma and discrimination experienced by people living with HIV (PLWH), some data suggest that they are also affected with chronic pain (23)(24)(25)(26), thus, predisposing them to frequent use prescription drugs such as opioids (27,28). Although, South Africa's National Strategic Plan for HIV, TB and STIs 2017-2022 is adopted in response to the HIV epidemic, the country is still far to the end of HIV (29).To date, South Africa accounts for about 19% of global HIV infections (30). Of the 7.9 million people living with HIV in South Africa, the KwaZulu-Natal province owns the highest HIV prevalence in the country of more than 2.1 million people are living with HIV (31). PLWH with opioid use disorder carries a double burden thus bringing complexity for treating and managing both epidemics.
South Africa has a National Drug Master Plan for 2013-2017 that is guided by the Prevention and Treatment of Drug Dependency Act (20 of 1992), and the Prevention of and Treatment for Substance Abuse Act (70 of 2008) (32). However, the drug law, policy, and law enforcement practices serve as barriers to implementing harm reduction strategies in order to fully address substance abuse as well as reduction of drug diversion, misuse and abuse (33). Despite the scrutiny and controversy from local officials, TB HIV Care Organisation has managed to implement the provision of free health services such as harm reduction, opioids substitution therapy and needle syringe provision programme among people who inject drugs at three sites in South Africa i.e. Cape Town, Durban and Nelson Mandela Bay (34). In addition to the HIV burden South Africa is faced with, it is imperative to understand the context of drug diversion, misuse and abuse. To date, research investigating the diversion, misuse and abuse of medicines either obtained over-the-counter or by prescription has been neglected to a large extent (5,16,(18)(19)(20). As a result, there is little available literature on the prevalence of drug diversion, misuse and abuse to support anecdotal reports in South Africa (22).
In the South African context, HIV control is the 1 st priority therefore the main objective of this study is to determine prescription drug diversion, misuse and abuse practices from the perspective of the multi-sectoral stakeholders in eThekwini district. Key stakeholder to be engaged would be the health care providers, law enforcement officers, pharmacists, current/past drug users and people living with HIV through in-depth interviews. Thus, understanding how each sector contributes, prevent and control the problem of prescription drug diversion, misuse and abuse. The study findings would bring awareness of the existing practices of prescription drug diversion, misuse and abuse to policy makers, health care personnel and lastly to the public.

Definitions
In this study, we define drug diversion according to Inciardi et al (2016) as the illegal manner of obtaining or distributing medicines for any use (35). Misuse of medicines is defined according to Casati et al. (2012) includes inappropriate use with or without a health care provider's instructions but clearly not adhering to the dosage instructions, time period or ways of drug administration therefore the risks are more significant than the benefits (36). Lastly, drug abuse is defined according to Akerele et al. (2017) refers to the non-medical use of medicines in quantities that might be fatal (37).

Study design
This is qualitative study that employed semi-structured interview guide to conducted face-to-face indepth interviews for data collection. We conducted this study was conducted in the period of June and December 2018. We recruited key stakeholders of prescription drug diversion, misuse and abuse in eThekwini district. We defined key stakeholders of prescription drug diversion, misuse and abuse as parties involved in medicine distribution and usage. Through the interviews, data was collected on and practice of prescription drug diversion, misuse and abuse. We used face-to-face, in-depth interviews as they can reveal new information, uncover hidden practices and provide insight into the topic, (38) which is imperative in understanding the perceived practices.

Study setting
Interviews were conducted with key stakeholders from eThekwini district, KwaZulu-Natal province in South Africa at the time of the interview. The population size of eThekwini district was estimated at 3.7 million in 2016 of which about 1.9 million people are living with HIV (31). One of the key challenges related to eThekwini district health care service provision is the high prevalence of HIV/AIDS and also abuse of drugs and alcohol (39). However, until to date the extent of prescription drug diversion, misuse and abuse in eThekwini district is unknown.

Study participants
Participants were eligible for the study if they were aged 18 years or older, reside in eThekwini district and were able to give consent to participate in the study. We aimed at enrolling key stakeholders highly likely to have encountered drug diversion, misuse and abuse. Therefore, our sample comprised of the following key stakeholders: primary health care providers responsible for HIV care, health care providers responsible for drug abuse treatment, pharmacists, law enforcement officers (analysts from the forensic department), past/recovering prescription drug misusers/diverters/abusers and people living with HIV. People living with HIV were chosen since they have numerous experiences with the health care system. We excluded those who were unwilling to give consent. Data was collected in English however other languages were permitted in order to allow full expression of participants' views.

Recruitment approach
Most participants were found through snow balling, referrals and purposive sampling excluding participants from the law enforcement department who were allocated by the commissioner. The above approaches were appropriate for the study due to the sensitive nature of the study topic and questions. Participants were invited to voluntary participate in the study. Invitations and appointments were made with potential participants via emails, text messages, face-to-face meetings or telephonically depending on feasibility. In cases where one agreed to participate in the study, an appointment date was scheduled for face-to-face the interview at their convenient space and time.
There were numerous declines from pharmacists due to their busy schedules. Meanwhile all street vendors or dealers of medications declined due to the fear of safety and the thought of being reported to the authorities. The study aimed to interview at least three participants per category until saturation was achieved. The study purpose was explained to the participant and informed consent was obtained before the interview commenced. In this study thematic saturation point was reached after interviewing 18 participants.

Data collection and instruments
Face-to-face interviews were conducted with each stakeholder. An open-ended interview guide asking questions related to existing practices and factors contributing to prescription drug diversion, misuse and abuse was used. However, the interview guide ensured that certain important aspects related to the topic were addressed during each interview. The interview guide used in our study has been included as an electronic attachment to this paper (see Additional file 1: Appendix 1). The interview guide was developed and modified to suite our study setting however most questions were adapted from several studies conducted in high-income-countries (40). The interview guide was designed to explore the key stakeholder's views on existing practices of prescription drug diversion, misuse and abuse. Therefore, our approach was an exploratory study.

Procedure
All interviews were conducted face-to-face with each participant in a private space at different places and time at their convenience. The researcher who conducted face-to-face qualitative data was trained thorough workshops and consultations with experienced researchers in qualitative study designs. Written consent was obtained from all participants prior to the start of the interview. All interviews were conducted in English however other languages were permitted to allow the participants to fully express themselves. Interviews were audio taped with permission and each lasted up to 60 minutes or less depending on the availability of the participant. Participants who were requested to travelled to the interview venue were reimbursed with R50 for their travels. All interviews were transcribed verbatim and translated into English in cases were a non-English language was used. The transcripts were analysed thematically using NVivo 12 software (41).

Ethical Considerations
The data collection process only commenced after obtaining the full ethical clearance from the

Data management, analysis, validity and reliability of analysis
The audio-taped interviews were transcribed into a Microsoft word document concurrently with data collection process so to allow for better judgement for data saturation. Data saturation point was reached when all participants were no longer giving new information and the study objective was addressed. In cases were a non-English language was used, the transcript was translated into English by the researcher (BC) and two research assistants (TS and SK). All transcripts were validated for accuracy by the researcher (BC), an independent researcher (TPM-T) and an independent research assistant (DD). Data analysis occurred after data collection process. The framework analysis method approach was followed during data analysis (42,43). The main advantage of using this method was that the matrix output will consist of rows (cases), columns (codes) and 'cells' of the summarized data (42,43). Therefore, providing a flexible systematic structure that can easily be manipulated. The disadvantage is categorizing data since this method cannot handle heterogeneous data therefore it is important to collect data that covers similar topics (42,43). Overall this method aimed to generate themes and the procedure for data analysis and the precise steps employed in the qualitative analysis of interviews are summarized in Table 1.  Notes of the key ideas and repeated themes were highlighted and taken.

Coding
The researchers were concerned with addressing specific research questions an analysed the data with that in mind.
Thus, this was a theoretical thematic analysis.
Given this, we coded data that was relevant to or captured something interesti our research question.
We did not code every piece of text.
We used open coding since we developed and modified the codes as we worked the coding process.
The main aim of coding was to categorize all collected data.
Coding, searching and retrieving data was facilitated by using NVivo 12 softwar Two researchers carefully read the transcripts line by line while taking note of paraphrases or label 'code' that were relevant and important. 4 Developing a working analytical framework Codes were grouped into categories.
These categories formed a working analytical framework.

5
Applying the analytical framework Analytical framework was used to perform indexing of all transcripts using categ codes. 6 Charting data into the framework matrix NVivo 12 software was used to generate framework matrices 7 Interpreting the data Characteristics of and differences between the data was identified.
Mapping and interpretation of the connections between categories to explore relationships and/or causality was done.

Participants characteristics
Eighteen residents of eThekwini district, KwaZulu-Natal, South Africa consented to participate in the in-depth interviews. Table 2 depicts the characteristics of the study population. Participants provided their perceptions of practices of prescription drug diversion, misuse and abuse. Fifty six percent (n = 10) of the sample were male, and 44% (n = 8) were female. Participant's age ranged from 19 to 74 years. The sample consisted of three people whom were living with HIV, three analysts from law enforcement, three health care providers from public health clinics, three doctors from drug treatment centres, two pharmacists (one from retail and the other from public health care facility) and lastly four recovering drug users.

Participant's understanding of drug diversion, misuse and abuse
Majority of participants in the health care profession viewed drug misuse as not taking medication as prescribed, using medication for purposes other than medical diagnosis, wrong dose, wrong duration and taking medication not for the appropriate indication. Most participants associated drug abuse with taking drugs in an addictive potential in order to have some sort of high, using drugs at higher doses, using drugs that are highly addictive with addictive potential or physical dependency. Very few participants were familiar with the term "diversion" however some associated drug diversion with using another patient's medication, using multiple facilities to collect medication, distributing drugs illegally, drugs taken for another use or by another user not according to policies and essential drug list (EDL). Interestingly, one participant viewed drug diversion as prescribing drugs while not using policies and protocols. Challenges and barriers to drug abuse treatment

Manifestation of drug diversion
Participants presented different manifestation of drug diversion, these include the following: surplus prescribed medications; incorrectly prescribed medications; and mixing codeine containing cough mixtures with anti-depressants to boost the effect or taking sleeping tablets to replace heroin effect.
A pharmacist described the legal channels of obtaining prescription medication and another participant described how he got involved in diversion.

Consumer's attitude and behaviour
Participants raised concerns about the consumers' attitude and behaviour towards health care providers when they require more prescription drugs to treat or cure their conditions. It was reported that consumers become aggressive, demanding, asking for specific drugs. It was also noted that most consumers who are addicted to prescription or over the counter drugs are in denial of their addiction problem.

Availability of medicines
All participants believed that medicines are readily available and accessed everywhere either via legal or illegal channels through facilities or dealers and emphasised that there is no need of a physical location. Most drug misusers prefer using the cheapest and easily accessible drugs, which can be obtained over-the-counter. It was also reported that illegal drug venders are also sell drugs during social grant collection targeting elderly people and introducing inappropriately packaged and unlabelled medicines.

Challenges and barriers to drug abuse treatment
Drug abuse is difficult to treat when patients don't take ownership of the underlined problem. Barriers such as inadequate knowledge of how treatment works, health systems barriers with pharmacies were by even after confrontation some pharmacies continued issuing the addictive products was the main concerned mentioned by drug users.

Discussion
To our best knowledge, this is the first study to provide an in-depth qualitative understanding of the existing practices of prescription drug diversion, misuse and abuse involving stakeholders from both medical and non-medical backgrounds in eThekwini district. The results suggest that drug diversion, misuse and abuse include both prescription and over-the-counter drugs and is a growing public health problem occurring to anyone through legal and illegal channels but mostly observed in private  (17). Despite that the misuse of codeinecontaining products was prevalent, our study has revealed other medicinal drugs with sedation properties which were diverted for illegal use in cases where illegal drugs were unavailable.
Therefore, putting drug users at increased risk of drug overdose since the legal drugs would need to be used in higher doses than normal. Although literature has shown that revenue generation predispose most drug stores to sell medicines to clients even without a doctor's prescription (44)(45)(46).
The reported accidental addiction might stem out from the fact that health care providers are challenged with disparities such as lack of specialized trainings (5,20) and lack of institutional guidelines (48). This study has also shown that consumer's attitude and behaviour as an additional challenge faced by health care providers. This translate into poor protocol implementation for most health care providers who shun away from conflicts with patients or costumers at pharmacy and weak enforcement of regulations and policies has being reported (16). On other hand, consumers' denial and dishonesty adds to the burdened health system gaps such as lack of screening tools (16), lack of monitoring systems (18), poor supervision (16) therefore perpetuating drug diversion problem.

Strengths and limitations
This study is the first in eThekwini district to highlight practices of prescription drug diversion, misuse and abuse from the perspectives of key stakeholders. It has presented novel drivers of prescription drug diversion, misuse and abuse such as consumer's attitude and behaviours probable in worsening the problem and a barrier to prevention of drug diversion, misuse and abuse. The participants recruited in this study varied in age, gender, race and occupation. It also included experienced health care professionals who are faced with the drug diversion problem daily. Moreover, this study was able to find participants to response to a study that raised a sensitive topic although conducting research about practices of drug diversion, misuse and abuse was a great risk since the law views it as illegal (32). We acknowledge limitations of the study, given the small sample size for each category due to challenges with recruitment and getting consent to participate in the study. Despite, the assurance of confidentiality, privacy and anonymity of data, most people feared of their safety since law views drug diversion as illegal. Most pharmacists in retail practice and all street vendors declined invitations. The study had to use referrals, snowballing sampling techniques as well as building trust.
A single researcher (BC) conducted all interviews therefore this might bring bias however an interview guide was used so to guide the conversation. Lastly, the study was conducted in eThekwini district, therefore the findings are not generalizable across KwaZulu-Natal province.

Recommendations
While the country is still in the midst of HIV/AIDS epidemic, it's of importance to pay attention to emerging public health threats such as prescription drug diversion, misuse and abuse so to develop proper and tailormade strategies to curb problem. Furthermore, addressing drug diversion, misuse and abuse would also address blood borne diseases especially Hepatitis B, Hepatitis C and the human immunodeficiency virus. We recommend future studies to further investigate each identified practice in order to gain more insight into the problem. We also recommend that policy makers should consider a collaborative approach involving all stakeholders affected by drug diversion, misuse and abuse since awareness and knowledge of potential drug risks alone is ineffective.

Conclusion
This study qualitatively describes practices of prescription drug diversion, misuse and abuse in eThekwini district. Prescription drug diversion and misuse is an emerging public threat with accidental addiction, health care system gaps and consumer's attitude and behaviours leading the problem therefore negatively impacting health care providers and consumers. We recommend a collaborative approach to address prescription drug diversion since the prescriber, dispenser, consumer and law enforcement are involved in the cycle to drug usage.

Declarations
Ethics approval and consent to participate and site clearance from all recruitment sites were obtained prior to data collection. All participants consented before data collection resumed.

Consent for publication
Not applicable

Availability of data and material
The datasets generated and analysed during the current study are not publicly available since this is a PhD study under examination.

Competing interests
None declared

Funding
University of KwaZulu-Natal for financial support, recourses and materials. National Research Foundation for financial support.

Authors' contributions
BC and TPM-T conceptualized and designed the study. BC conducted literature search, data collection.
BC and TPM-T analysed data and interpreted results. BC prepared the first manuscript draft including figures and tables which were reviewed by TPM-T several times until ready for submission. P