Addressing conflict of interest driving irrational prescribing of antibiotics in pluralistic health systems: an interventional study in Pakistan

The study proposed here applies cutting-edge health policy and systems research to address a critical and poorly addressed global health challenge: conflict of interest (COI) hindering improvements in the quality of care delivered by private healthcare providers. We define COI as a situation whereby the impartiality of a healthcare provider's judgment may be influenced by a secondary interest, such as financial gain, leading to a decision that is not in the patient's best interest. There is strong evidence that private doctors seeking to make a profit from patient consultations often experience a COI resulting in prescription of medication or diagnostic tests that are either unnecessary or more costly than available alternatives. We focus on irrational prescribing of antibiotics by private doctors in Pakistan, the sixth most populous country in the world, where more than 80% of people first seek care at private doctors and where antibiotic usage is among the highest in the world. Studies in Pakistan and other low and middle income countries, including our own earlier research, show that private doctors prescribe multiple antibiotics when patients do not need them in order to receive benefits from pharmaceutical companies, or make profits from the medicine sales.

Despite the scale and urgency of this issue, which affects millions of people and drives antimicrobial resistance which can spread across the world, there is extremely limited evidence on strategies that are effective in contexts where resources and political support for the enforcement of rules are low. Therefore, training interventions focusing on increasing knowledge and skills to affect voluntary behaviour change in private providers is the most common approach used. However, these interventions have had limited success when irrational prescribing is mainly motivated by profit-generation rather a lack of knowledge; here norms and values associated with professional ethics are critical to address with interventions.

Our study has four linked objectives, which together will generate new evidence about the impact of a continuing medical education intervention with specially designed messages to sensitise doctors to professional ethics and COI, as well as critical insights about barriers that need to be overcome in order to facilitate scale-up of this intervention in the local health system. Since influential stakeholders responsible for addressing practices of private doctors may be crossing professional ethics boundaries themselves, often by having multiple income streams without disclosure, our first objective is to understand how COI and professional ethics is conceptualised by influential stakeholders in Pakistan in order to identify potential supporters and opponents of our intervention. We next focus on private doctors, investigating how they decide what is ethically unacceptable and acceptable with respect to getting personal benefits from prescribing antibiotics. Our third objective is to understand how best to present messages that sensitise private doctors to professional ethics and the role of conflict of interest driving irrational prescription of antibiotics in order to design our intervention. Our final objective is to assess the impact of our intervention on the behaviour and attitudes of private doctors with respect to unethical benefits from pharmaceutical companies for prescribing antibiotics.

A key strength of the proposed study is that it has been co-designed with Pakistani researchers and policymakers, building on two previous research council funded projects in Pakistan and Cambodia. In addition to producing new evidence to inform ongoing investments in improving quality of care and tackling antimicrobial resistance, our medical education material on COI can be used for research and training in other settings, and the tools developed as part of our innovative health systems research methods will be made available for future studies.

Health systems research and the design of interventions to improve quality of care has typically focused on the hardware of health systems, even though it is known that the software, including values and culture, is critical. Our research is situated at the intersection of two 'wicked problems' - governance of private providers and antimicrobial resistance - and addresses conflict of interest (COI) driving irrational prescription of antibiotics by private doctors in Pakistan. Being cognisant that regulatory bodies in many low and middle countries are unable to effectively enforce rules, we view soft governance approaches as being essential to the internalisation of voluntary ethical rules of behaviour.

We start by applying innovative qualitative methods, involving vignettes and a card placing exercise, to facilitate rich data collection that will inform the design of an evidence-based soft governance intervention. Data from policy actor interviews will be used to conduct a stakeholder analysis examining actors' positions on tackling COI in private doctors, paying attention to vested interests that lead to governance conflicts. Interviews with private doctors will investigate how health systems dynamics - such as reliance on pharmaceutical companies to support professional development - shape their perceptions of ethically acceptable COI with respect to prescribing antibiotics. These interviews will also enable an analysis to inform how messages that sensitise doctors to professional ethics and COI should be framed. We will embed these messages into a continuing medical education seminar (our intervention), and conduct a randomised controlled study to compare behaviour of doctors who attend the intervention seminars with those who attend placebo seminars with no mention of COI. We will generate robust evidence on the impact of our intervention by using a novel objective assessment of doctors' behaviour vis-à-vis receiving benefits for prescribing antibiotics.

Our ultimate impact will be on populations in low and middle income countries (LMIC), where 9 million deaths occur annually due to poor quality of health services. While better functioning of the dominant private sector is critical to improving healthcare in LMIC, strategies to govern private providers often fail because complex social and political factors that hinder progress, such as conflict of interest (COI) influencing medical decisions, are rarely considered. Owing to its huge economic and social cost, global and national policymakers are making large investments into tackling antimicrobial resistance (AMR). Therefore, stakeholders focused on AMR and global health security, as well as those concerned with health systems strengthening, are seeking evidence on interventions to address quality of private healthcare and irrational use of antibiotics.

We will maximise impact through outputs designed for key decision-makers and practitioners, and groups that influence them:

1. Global policy agencies such as the World Health Organization and the UN Interagency Coordination Group on AMR
2. Pakistani policy and regulatory bodies
3. Ethical pharmaceutical companies
4. Healthcare professionals and health programme managers in LMIC
5. Funders of research and programmes on health systems strengthening and antimicrobial resistance in LMIC
6. Academics that advise policymakers and funders
7. Media

Our outputs will include:

1) Evidence on the impact of a continuing medical education intervention - jointly designed with policy actors, private doctors and project partners - to address COI driving irrational use of antibiotics by private doctors
2) Development and application of a new method to objectively assess interactions between doctors and pharmaceutical sales representative
3) A medical education presentation on COI that can used by medical schools and regulatory bodies
4) Vignettes representing COI situations that can be adapted for future studies on professional ethics in diverse settings
5) A stakeholder analysis identifying governance conflicts with respect to policies to reduce irrational use of antibiotics.

Attention to scalability and addressing barriers to research uptake have been built into this project. We have already mapped stakeholders that influence policies on access to antibiotics, and we have convened five meetings in Pakistan since 2016. Through our earlier research we found that there was broad support from Pakistani policy actors to address COI influencing private doctors' prescribing decisions, and specific demand for us to develop and test the impact of a continuing medical education seminar to sensitise private doctors to COI. Thus, we are already well placed for high policy impact, being closely engaged with regulatory agencies and AMR working groups in Pakistan and internationally. Our project partner, the Sindh Healthcare Commission, is responsible for regulating doctors in the province and will collaborate with us on developing and testing our intervention to inform plans for rolling it out in the province. As part of their current roles, S Siddiqi (an adviser to the Minister of Health) and Hasan (a technical expert guiding development of national AMR strategies in Pakistan) will be able to frequently share findings with policymakers. Ethical domestic and international pharmaceutical companies have expressed an interest in supporting scale-up as they would benefit from changes in doctors' expectations of financial benefits in exchange for prescribing. Furthermore, project partner Zaman, health adviser to the Prime Minister, will facilitate incorporation of evidence generated from this project into relevant reports for politicians. Since continuing medical education seminars are popular with doctors in numerous settings, there is an existing system for scale-up in Pakistan, and in other countries.