In its Global Risk Report 2013 , the World Economic Forum (WEF) concluded that antibiotic resistance poses a major risk to human health. PwC’s analysis of this case study, highlighted the particular danger of complacency over antibiotic resistance – or more broadly, antimicrobial resistance (AMR)  – with many people assuming that advances in medical science will enable us to stay one step ahead of new and evolving diseases or novel pathogens.
Many recent events have called this presumption into question.
In 2012, an outbreak of K. pneumonia, an antibiotic-resistant superbug, killed 18 people at the U.S. National Institutes of Health’s Clinical Center in Maryland. In the same year, physicians at Hinduja National Hospital in India reported that 12 patients had contracted a form of tuberculosis (TB) that had not responded to any known TB treatment; three of the cases proved fatal.  Subsequent tests confirmed that eight of these patients had contracted total drug resistant (TDR) TB, meaning they were resistant to all known first and second-line TB medications. 
The combination of AMR pathogens and other infectious diseases can produce an even greater threat. A 2011 study showed that many of the 2009-2010 H1N1 influenza pediatric deaths occurred among children who had also acquired antibiotic-resistant bacterial infections. Examining 838 pediatric intensive care cases across the U.S., researchers found that simultaneous infection with methicillin-resistant staphylococcus aureus (MRSA) bacteria in the children’s lungs produced an eightfold increase in the risk of death. 
In addition to having severe public health consequences, such disease outbreaks can have tremendous economic implications both for companies and for countries. Outbreaks may result in a sharp rise in lost time at the workplace, reduced travel and tourism, a downturn in trade, over-burdened hospitals, increased insurance premiums, and increased rates of death and disability. Unlike other risks like earthquakes, hurricanes or nuclear or chemical threats, infectious diseases spread. The 2002-2003 outbreak of Severe Acute Respiratory Syndrome (SARS) is estimated to have resulted in losses of $50 billion worldwide .
Given the impact of disease on both health and the economy, individuals, corporations, national governments and international organisations have a shared interest in combating AMR. However, despite the common understanding that AMR is brought on by overuse, stakeholders are incented to act in their own interest rather than the common good. Patients will seek treatment if ill, clinicians will prescribe, pharmacies fill and drug companies sell, without consideration for the potential longer-term impact.
Initiatives undertaken to address AMR have mostly been voluntary and have been impeded by a lack of coordination and integration. We need to take concerted action now before it’s too late. Antimicrobials are a limited resource that we risk depleting, and once we do so, we will be hard pressed to recover. The dangers are heightened by the fact that the current antimicrobial pipeline is weak. As such, the challenge of becoming resilient in the face of an increase in AMR has taken on increased urgency, presenting a critical frontier in the on-going battle to preserve the length and quality of human life.
In PwC’s response to the WEF case study, we take an expanded view to focus on the underlying threat of novel pathogens. First we move beyond bacteria, against which only antibiotics are used, and include all pathogens such as viruses and fungi, against which antimicrobials are used. Overuse of antimicrobials increases the natural rate of mutations of genes in pathogens. It is this man-made acceleration in evolution that has resulted in the higher incidence and prevalence of novel pathogens against which our existing arsenal of antimicrobials and diagnostics can have diminished or no efficacy.
Yet AMR is just one of three main catalysts for the accelerated emergence and evolution of novel pathogens we’re seeing today. The second factor, increased contact between human and animal populations, as well as travel, has created an environment where pathogens are readily passed between species — a global mixing bowl of pathogens. Finally, genetic engineering and synthetic biology provide the ability to custom-build microbes, including novel man-made pathogens.
To address the unprecedented acceleration in the emergence and evolution of novel pathogens, a more comprehensive approach is needed. Recognising the global nature of the threat and the multitude of contributing factors, the World Economic Forum and the World Health Organization have called for a solution that involves greater international and multi-stakeholder collaboration. Recommendations include creating public-private partnerships, and embarking on international efforts to reduce barriers to drug development, to name but a few.
In our response to the WEF case study, we recommend adding structure around this collaboration, outlining a basic framework for a robust, comprehensive, and integrated response built around the pillars of detect, develop and deliver. This framework addresses the capabilities needed to become resilient against these novel pathogens — to continuously and rapidly identify, characterise, develop and make available treatments against them. It also looks at how to re-align incentives to reduce the activities that are unnaturally accelerating the creation of the novel pathogens.
In this article, we will expand upon this framework by:
The call for an international and multi-stakeholder solution in the fight against resistance is much more challenging in practice than in theory. A structured approach toward addressing this challenge can facilitate both planning and execution. We propose that any effective solution include the following elements:
1. What needs to be done? A balanced approach that spans the continuum of care: Detect, Develop and Deliver:
An imbalance in any of these elements, represented by insufficient resources or outcomes, will result in an incomplete and ineffective solution. For example, governments may build state-of-the-art biosurveillance capabilities, but without treatment or an effective mechanism for delivery, the root causes contributing to resistance will not be addressed, and the problem will persist and worsen. Rather, in a comprehensive response, all three elements must be present and working as intended.
2. Who should be involved? Responsibility for combating the problem isn’t isolated to governments or health systems, but rather must involve a comprehensive and coordinated ‘ecosystem’ approach. This implies combined and synchronised efforts from all stakeholders involved in the Detect-Develop-Deliver spectrum, which broadly includes the private sector, public sector and healthcare providers (HCPs). While PwC’s response to the WEF case study generally introduces the reader to each stakeholder group, this article will detail the roles and responsibilities of each group, as well as explore the role that each stakeholder should play in risk mitigation.
Each stakeholder group identified in our analysis plays a role in each of the Detect, Develop and Deliver pillars, though some are especially prominent (Detect – public sector, Develop – private sector, Deliver – HCPs). Primary stakeholders are often supported by secondary actors that may play an equally important, albeit indirect role.
Acknowledging and understanding the role that each actor should play within each pillar of response is critical to building resilience. Practices aimed at improving resilience should consider the unique challenges that prevent each stakeholder from performing the role required to combat resistance, and should focus on establishing incentives for stakeholders to perform activities outlined in Figure 1 below and described further in this article.
Figure 1 - Outlining roles and responsibilities
Private sector: While the private sector is generally a secondary actor in detection, it is a consumer of information gathered by other stakeholder groups. The private sector can use this information to improve market forecasting and, in turn, profitability. Increased and early visibility of the spread of a novel pathogen will reduce the availability of the existing armamentarium of treatments — or lead times associated with R&D, regulatory approval, distribution and dispensing, policies for new diagnostics and concomitant treatment. In the absence of full access to data related to emerging trends and potential demand, private sector actors may not have meaningful incentives to invest in product development.
Public sector: Public sector actors play a primary role in the detection phase. Roles and responsibilities typically include implementing disease surveillance systems, facilitating the exchange of information, monitoring product usage and identifying, monitoring and communicating trends. National borders and differences in regulatory systems, however, present a challenge to international collaboration and information sharing, and may negatively impact the timely dissemination of data across the stakeholder ecosystem, including to the HCP community.
Health care providers: HCPs are also secondary actors in detection, although their role in this pillar is critical. Since infected patients will typically seek treatment through a number of channels, any single HCP will not have access to, or visibility of, the full range of data that can ease the identification of emerging trends. However, by recording information and reporting to relevant authorities in a timely manner, HCPs can speed up the process through which the spread of a pathogen is identified. Ineffective communication between the public sector and HCPs may result in delays associated with accurately diagnosing a disease — leading to the use of antimicrobials where not appropriate, or exacerbating the problem of resistance.
Private sector: The private sector is a primary actor in the development of new medicines, platform technologies and kits that enable effective diagnosis and treatment of diseases. However, since limited commercial incentives exist for developing new antimicrobials, private sector actors are generally more focused on developing treatments for which there is a longer duration of care (e.g., non-communicable diseases). Such circumstances result in a limited pipeline for new and innovative products.
Public sector: Public sector actors play a secondary role in antimicrobial development. Roles and responsibilities include performing early-stage research and development (R&D), providing funding/incentives for advanced-stage R&D, sharing best practices and encouraging dialogue between public and private sectors. Regulators may introduce incentives/approaches to facilitate R&D through initiatives such as priority review vouchers and conditional approvals incentives. Public sector challenges include justifying time and resources spent on addressing this challenge at the expense of other priority efforts and initiatives.
Health care providers: HCPs collect, catalogue and store biological material for the purpose of laboratory research. HCPs may help perform clinical trials and can share lab results pertinent to research and development. HCPs may also be involved in development in that they can contribute/specify requirements (Target Product Profiles) for therapeutic interventions. Challenges primarily include the timely sharing of information with product developers, and the availability of accurate diagnostics to ensure appropriate treatment.
Private sector: The private sector is a secondary actor in the deliver pillar. Once products have been developed and tested, and have cleared all necessary regulatory hurdles, the private sector has a vested interest in marketing products to increase potential sales. Product developers are also responsible for manufacturing and delivering products to the market and for developing competitive pricing strategies. These organisations play a critical role in assuring the affordability and availability of key drugs in global markets, and in educating consumers on appropriate use. Private sector actors also have a commercial incentive to protect against counterfeit/sub-par quality drugs — another factor contributing to increased resistance. Barriers to full private sector participation in delivery include insufficient manufacturing and delivery capacity to meet global demand, limited commercial attractiveness in some markets, and poor delivery infrastructure to some locations.
Public sector: Public sector actors play a secondary role in the deliver pillar, encouraging the adoption of consistent standards and policies to be adopted by national and local governments related to proper dispensing, rational use and aligning health system incentives. Public sector organisations often take a lead role in educating patients on appropriate use of products, and can facilitate Public Private Partnerships (PPPs) focused on improving access to and availability of products. Regulators issue guidance on quality management standards to combat counterfeit products. Challenges include coordinating and standardising policies across governments and other public health organisations that are required for a consistent and systematic response.
Healthcare providers: HCPs play a primary role in the deliver pillar, as they are the closest to the patient. HCPs are responsible for diagnosing diseases and prescribing the appropriate courses of action. Formularies play a direct role in educating patients that seek treatment at hospitals, clinics, and/or pharmacies. They are responsible for implementing guidance and policy dictated by the public sector. Misaligned doctor and health system incentives and the limited availability of accurate diagnostics may result in inaccurate diagnoses and can result in inappropriate treatment.
This series of articles is intended to inform and motivate. As a collaborative ecosystem of stakeholders, we are all involved in the fight against AMR irrespective of whether or not we work in the organisations spotlighted in this article.
We are patients and families of patients. We are active in our communities, and are international travellers. We are business leaders looking out for our workforces and our revenues, and online global citizens with the means to influence. Understanding the role that we each play in the ecosystem is an important first step. Following from this understanding, we must develop a coordinated and integrated action plan that addresses the challenges and barriers that might cause us to deviate from these roles.