The burden of cancer is increasing globally, making the search for new oncology therapies a major priority for the research community and a consistent area of investment for pharmaceutical companies. In 2018, over 138,000 people in Australia were diagnosed with cancer and over 48,000 people died from cancer (1). There were approximately 130 cancer treating medicines available on the Pharmaceutical Benefits Scheme (PBS) in 2018, of which 70 have been approved since 2013 (2). This is an indication of the accelerating pace of new drug discovery in oncology bringing new therapeutic options to healthcare professionals (HCPs) and patients. However, this deluge of new therapies can also leave HCPs, patients and payers with many questions around how these therapies perform in real world clinical practice.
Randomised controlled trials (RCTs) are the gold standard for informing regulatory approval of new therapies and expanded indications for already approved therapies. However, they are costly and time intensive and since studies include a limited patient population who meet specific criteria there is often an evidence gap between clinical research data and real world clinical practice outcomes (3). This evidence gap coupled with the increasing need to provide timely access to new therapies, particularly in the oncology space, has led to the need for real world data (RWD). RWD is useful for payers as a supplement to existing RCT data to show the clinical and cost-effectiveness of therapies over an extended time frame.
RWD is data relating to patient health status and/or delivery of health care generated outside of conventional RCTs. This data can be derived from a variety of sources including patient registries, electronic health records (EHRs), insurance data, as well as mobile applications and devices (4). RWE is generated from these data sources and potentially used to inform regulatory and reimbursement decision making. RWE supplements RCT data by providing information on disease progression and overall survival over extended time periods (5). RWE is also useful where large RCTs are not feasible, such as assessment of treatment effectiveness in rare diseases, niche indications and patient subgroups (5).
Many countries have implemented programs for the collection and analysis of RWD via patient registries. Some have also developed strategies for use of RWE to capture information relevant for research and drug discovery, as well as regulatory and reimbursement decisions. For example, in America the FDA recently published a framework for its ‘RWE Program’ to inform the strategic use of RWE to enhance regulatory decision making (6). In England, the National Cancer Registration and Analysis Service (NCRAS) was launched in 2013, which provides comprehensive clinical information on all 350,000 people diagnosed with cancer in England each year, as well as 141 million historical cancer records (5).
In Australia, the Therapeutic Good Administration (TGA) has implemented an expedited ‘Provisional Approval pathway’ for the registration of new medicines in certain circumstances such as in the case of innovative cancer therapies (7). Providing timely access for patients to often highly expensive drugs also requires clinical and cost-effectiveness assessment by the Pharmaceutical Benefits Advisory Committee (PBAC) prior to reimbursement listing on the PBS. Although there is no formal framework for the use of RWE in Australia, there have been several instances where the PBAC has requested post-marketing RWD to enhance the clinical and cost-effectiveness evidence for certain cancer drugs to track especially longer term outcomes.
One example of the successful use of RWE involves the immuno-oncology drug ipilimumab for treatment of patients with malignant melanoma, which was approved on the Managed Entry Scheme (MES). Inclusion on the MES involved a risk-sharing ‘pay for performance’ arrangement whereby rebates would be payable should the two-year overall survival rates in real world clinical practice not align with the RCT outcome. To meet this requirement the sponsor collected RWD from consenting patients prescribed ipilimumab over the 2-year follow-up period. In this case, patients’ overall survival, the gold standard endpoint in RCTs, was supported by the RWE.
This is an example of the value of RWE in removing payer doubts around clinical and/or economic effectiveness, thereby benefitting patients through earlier access to subsidised medicines.
CRC’s experienced Medical Affairs team has the expertise to identify and work with key stake holders to understand where evidence gaps exist and develop strategies for generating RWE to inform reimbursement decisions.
My Health Record (MHR) is a new secure online summary of consenting individuals’ health information, enabling centralised storage of health documents such as hospital discharge summaries, pathology reports, prescription documents, organ donor registration details and Medicare documents (1). While there are many benefits to implementing MHR, there are also concerns around the secondary use of data, as well as cybersecurity, data errors, risks to patient safety and medico-legal implications for healthcare providers (HCPs).
Aligned with the increasing focus on patient centricity among pharmaceutical and medical device companies, there is a need to access better patient data and develop an improved understanding of the patient journey. In this brave new digital age, electronic health records provide a rich data source of insights about the impact of treatments on patient outcomes. However, there is a disparity between the perception of big data as the ‘holy grail’ for insights and an apparent lack of confidence among consumers and HCPs in committing their information to MHR, given recent public debate.
The age of digital healthcare is upon us and many countries have implemented centralised electronic health records systems, similar to MHR, to integrate health data from multiple sources that is accessible by relevant stakeholders. Peak health bodies including the Australian Medical Association, the Royal College of Australian GPs and the Pharmacy Guild of Australia are in support of MHR for its potential to positively impact patient care and support practitioners (2). Australia has approximately 230,000 medication misadventures a year costing the healthcare system $1.2 billion (3). It is hoped that one of the many advantages of implementing the MHR system in Australia will be a reduction in these costly, often preventable adverse drug events.
The intention is that each individual’s record will eventually be populated with data that provides a complete digital health record in one place that is accessible to all relevant HCPs. With more work, the system should provide timely access to health information which saves vital time in emergencies and allows for more time spent treating patients. Enabling doctors to see a range of clinical, prescription and health information about a patient should reduce medication errors, as well as unnecessary duplication of pathology and imaging tests (4). Community pharmacists will also benefit through access to clinical information in a shared health summary which is useful for performing MedsChecks and Home Medication Reviews (4).
The perceived benefits of the MHR system have been largely overshadowed in the media by concerns around data security and misuse of data. To ease concerns around data privacy, the Australian Parliament introduced amendments to prohibit insurers and employers from accessing records. Only certain government agencies can access records including the Australian Digital Health Agency, the Department of Health and Medicare. Additionally, law enforcement authorities require a court document to access information, all access to the system will be logged and heavy penalties will be imposed on those who access information illegally.
Despite these safeguards, vulnerable communities including those with mental health issues, people with HIV and victims of abuse or domestic violence remain unconvinced that their data will remain secure. The issue of accountability for medical errors caused by incomplete or incorrect data also remains unresolved. Good medical practice relies on accurate information, and in situations where multiple people can enter and edit data the potential for error increases. GPs have raised concerns about the medico-legal implications in situations where treatment decisions based on incomplete or inaccurate information cause harm to a patient (5). Uncertainty remains around medical indemnity, malpractice liability and what recourse is available to patients if mistakes are made.
Nevertheless, My Health Record, is a reality and so it is hoped that the various concerns raised can be resolved over time.
CRC’s experienced Medical Affairs team has the expertise to understand and utilise digital healthcare data for the purpose of demonstrating therapy value and supporting Medical Affairs related projects.
Artificial intelligence (AI) is set to bring a paradigm shift to the healthcare industry facilitated by technological advances, the availability of vast amounts of healthcare data and rapid development of big data analytical methods (1). AI systems analyse immense amounts of data from an array of sources to draw connections and predict outcomes which can be applied in several ways to healthcare (1). AI involves the use of software and algorithms to analyse data in a way that aims to mimic processes related to human intelligence such as reasoning, learning and adaptation, sensory understanding and interaction (1, 2).
Different AI techniques can be applied to healthcare data in structured and unstructured formats. Machine learning (ML) is useful for analysis of structured data from diagnostic imaging, genetic testing and electrophysiological data. Natural language processing (NLP) is used to analyse unstructured data such as clinical notes or medical journals by turning text into machine-readable structured data (1). The application of these technologies has great potential to unlock clinically relevant information in healthcare data from multiple sources to assist in clinical decision making (1).
There are challenges that must be overcome before the full potential of AI in real-life healthcare applications can be realised including privacy issues relating to the storage, use and sharing of sensitive health data, as well as the lack of adequate regulatory and legal frameworks. In America the FDA has approved a number of healthcare algorithms, however the guidance on how these algorithms are being reviewed and regulated has been described as unclear by industry stakeholders (3).
For example, AI technologies based on ML algorithms that are designed to learn from patient data and adapt as increasing amounts of data are analysed (4). Systems such as this will need to enable sharing of sensitive patient data while keeping protected information safe in compliance with government privacy regulations. A further challenge is developing a framework for how ML algorithms should be regulated and implemented in clinical practice, since these algorithms incorporate ‘new learning’ and adapt in response to increasing amounts of patient data (4).
In Australia, current Therapeutic Goods Administration (TGA) regulations do not adequately capture all ‘Software as a Medical Device’ (SaMD) under the risk-based classification used for medical devices. At present many SaMD products are classified by the TGA as low risk even though the potential risk for users may be higher. Therefore, the regulator will soon be consulting on changes to the regulations relating to emerging technologies including diagnostic AI systems, as well as health apps and 3D printing of body parts (5).
The first AI-based diagnostic system designed to provide an autonomous screening decision without the need for clinician interpretation was authorised by the FDA in 2018 (3, 6). The technology enables automated analysis of images to detect fluid on the retina for the detection of diabetic retinopathy, which is the leading cause of vision loss in adults. Diabetic retinopathy represents a significant healthcare challenge and will affect an estimated 191 million people globally by 2030. The software provides a quick result indicating that either diabetic retinopathy is present and the patient should be referred to an eye care specialist, or that the screen is negative and should be repeated in 12 months (6). In this case AI provides a result that can be interpreted by a non-specialist, making it feasible that patients could be screened in the primary care setting thus easing the healthcare system burden and potentially lowering costs.
It is increasingly evident that Medical Affairs will have a unique and expanded role in the healthcare industry as digital technologies such as AI transform how healthcare is delivered, as well as how drugs are researched and discovered.
CRC’s experienced Medical Affairs team has the expertise to provide tailored strategic solutions and communicate the value of clients’ products that incorporate artificial intelligence and other new age digital healthcare innovations.
Healthcare systems globally are facing numerous challenges. Among these is managing the health of ageing populations and a growing number of people with chronic lifestyle related diseases, which are placing increasing pressure on healthcare budgets. As 2019 fast approaches, it is timely to reflect on the evolving role of medical affairs as a strategic function in an increasingly complex healthcare landscape.
Some key challenges facing healthcare stakeholders include responding to complex changes in health policy and regulations, engaging consumers and improving the patient experience, as well as implementing more outcomes focused value-based healthcare models (1, 2). Precision medicines represent a new era of therapies that have emerged in recent years as a result of innovative medical research and are challenging the status quo of the healthcare landscape. These therapies require patients to undergo testing with a companion diagnostic to enable selection of those patients who will benefit the most from treatment (3). This maximises the value of medicines by way of delivering improved health outcomes and/or quality of life for a cohort expected to positively respond, while it may also lead to reduced healthcare costs whereby ineffective treatments and other interventions are avoided.
Australians have also indicated their readiness to embrace elements of the modern healthcare landscape with 75% of people in a recent poll claiming they are willing to use genetic testing to identify the most effective drug for their treatment needs, while 95% would share their test results to improve treatments for future patients (4). From a pharmaceutical industry perspective, it is suggested that industry has a presence on the Medical Services Advisory Committee (MSAC), which is the body responsible for appraising new companion diagnostics, as well as novel cell-based therapies such as CAR-T cell therapy (5). Such a move could enable improved feedback to companies from the Committee that would help to inform strategic medical affairs plans.
The medical affairs function is recognised as increasingly important in bridging the clinical and commercial interests of pharmaceutical and medical device companies to enable effective communication of the value of their products with a variety of stakeholders. To achieve this, medical affairs teams are increasingly drawing on not only clinical and cost effectiveness data, but also real-world evidence (RWE) or patient-outcomes data gathered outside of randomised controlled trials (2).
With a growing focus on implementing outcomes-based healthcare models, companies are placing emphasis on understanding the patient journey and seeking to add value at various touch points along this journey with their therapies. In addition, they are also focused on providing tailored support such as various digital tools in aiming to ease the burden of disease management. RWE can help provide a more holistic view of the patient journey and highlight the benefits of a treatment regime (therapy and any additional supports), as well as assist in communicating therapy value to relevant stakeholders.
The New Year is promising an influx of therapies awaiting regulatory approval from the TGA (6). However, securing registration approval is only the beginning for companies seeking to commercialise healthcare products in Australia. Forward thinking healthcare companies increasingly understand the necessity to invest in implementing a well-planned medical affairs strategy to help maximise therapy value in contributing to the achievement of commercial goals.
CRC’s experienced Medical Affairs team has the expertise to provide tailored strategic solutions across the entire product development life cycle that extract maximum value for our clients’ product portfolios in contributing to commercial success.
An increasing focus on biological therapies in recent years has meant that many pharmaceutical companies have scaled down their efforts to research and develop chemically synthesised “small molecule” drugs (1, 2). Biological therapy sales generate an increasing portion of pharmaceutical market share and arguably the most interest, yet they currently treat a limited range of diseases and can also be prohibitively expensive and inaccessible to patients if not reimbursed.
Media reports about innovation in the pharmaceutical industry are often prolific with acronyms such as CAR-T, PD-L1, PARP, CRISPR and mAb in referring to a range of cell based, biological and gene editing therapies. These therapies capture the imagination and draw attention for introducing innovative never-before-seen ways to treat serious disease. However, many of these treatments have yet to be tested by long term real world post-market use, while some can also cause serious side effects that negatively impact patient quality of life.
In 2017, the ten most prescribed and commonly used drugs in Australia were “small molecule” therapies (3). These are mostly well established drugs proven to be effective in treating common and chronic disease symptoms. However, small molecule doesn’t necessarily mean old drug (1). Indeed, there are a growing number of companies focusing on developing new, cutting edge chemically derived drugs. For example, ivacaftor is a small molecule drug tailored to treat specific subsets of people with cystic fibrosis for the first time targeting the underlying causes of the disease.
Another company has shown that an innovative approach to delivering of a small molecule drug via inhalation could set their product apart from competitors (4). This therapy is designed to block a molecule highly expressed in cells involved in scarring in the lungs of people with idiopathic pulmonary fibrosis (4). Another approach is to revamp and improve old drugs such as platinum chemotherapy which is effective but highly toxic resulting in side effects that can limit a patient’s tolerability to treatment. Clever reengineering of platinum chemotherapies could enable their targeted delivery in a way that effectively kills cancer cells thus limiting toxicity to patients (5).
Media reports often praise biological therapies or “large molecules” as providing ground breaking healthcare solutions, yet the above mentioned cases are just three examples showing that “small molecules” too can play in this space and compete with the “big guns” in the innovation stakes.
CRC’s experienced Medical Affairs team has the expertise to bring the value story of new molecules, big and small, to life via evidence generation initiatives and solid communication strategies.
CRC provides Medical Affairs solutions to the Pharmaceutical industry throughout the Drug Development Life Cycle. Our objective is to maximise the value of therapeutic compounds from pre-launch through to commercialisation and beyond.
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