National Diabetes Week kicks off 14th of July 2019 and this year Diabetes Australia is saying “it’s about time” for us to take action on diabetes with early detection and treatment.¹

Australia’s National Diabetes Strategy released in 2015 was described as “a once in a decade opportunity to strengthen the fight against the nation’s biggest health threat”.² The strategy articulates seven key goals and potential areas for action to reduce the social, human and economic impact of diabetes in Australia. However, implementing this strategy and in a systematic way remains a challenge.

Adding to this challenge is a perceived lack of unawareness among people of the significance in preventing and managing diabetes. For example, ask an Australian adult to list the diseases they most fear being diagnosed with and they would probably name cancer, heart disease, stroke and dementia. Few are likely to include diabetes on such a list. Most would also be surprised to learn that diabetes was an underlying and/or associated cause of one in ten Australian deaths totalling 16,400 in 2015.^3,4

Since 2008, diabetes has ranked seventh in the leading causes of death in Australia and, unlike heart disease, bowel cancer, or cerebrovascular disease, the number of deaths from diabetes is increasing.⁵

Diabetes is the fastest growing chronic condition in Australia, with more than 100,000 new cases diagnosed  in  the  past  year.⁶ In 2017-18, one in twenty  Australians (4.9% or 1.2 million people) had diabetes of any type.⁷ Many Australians with diabetes have a family member or carer supporting them, meaning an estimated 2.4 million Australians are affected by diabetes every day in some way.⁶ In addition, another estimated 500,000 Australians have “silent” undiagnosed diabetes.⁶

Disease and cost burden

Of the three main forms of diabetes – type 1 (T1), type 2 (T2) and gestational diabetes – T2 represents 85-90% of all cases and is generally a progressive condition of older adulthood, whereby the body gradually becomes resistant to, and/or unable to produce enough insulin.⁸

If left untreated or poorly managed, T2 diabetes can become a gateway to many life-ending medical events, not least of which are heart attack, stroke and kidney failure.⁹ Cardiovascular disease is the primary cause of death, with around 65% of all cardiovascular deaths in Australia occurring in people with diabetes or pre-diabetes.¹⁰

Other major complications include nerve damage, limb amputation, depression, anxiety and blindness, all of which have a significantly detrimental impact to quality of life and productivity.^9,10 Unlike T1 diabetes which is an autoimmune condition, T2 is generally associated with obesity, high blood pressure and low levels of physical activity, yet may be largely preventable by maintaining a healthy lifestyle.^9,10

Not to mention the cost. While there are no estimates of the current diabetes cost burden in Australia, the total annual cost of diabetes among Australians aged 30 years and over in 2005 was estimated at $10.6 billion, which in 2018 equated to $20.2 billion.^11,12 This includes direct healthcare and non-healthcare costs, as well as government subsidises, yet excludes lost productivity. As the diabetes burden continues to escalate, the $1.2 billion per year loss in lost gross domestic product from this disease in 2015 is expected to climb to $2.9 billion by 2030 due to its impact on lost work productivity.¹³

A different approach

Maybe T2 diabetes has an image problem? As a disease which can initially be managed with lifestyle (e.g. food changes, exercise) changes, T2 diabetes may be unlikely to inspire much fear compared with a diagnosis of cancer.¹⁰ Indeed, it may not impact the psyche of many Australians who are still ignoring the signs that they may be at risk of developing diabetes.

Perhaps community initiatives such as “The Community Health Challenge” started by one forward thinking pharmacy in Queensland is the key to helping people understand their diabetes risk and the adverse consequences of the condition if not properly managed or even diagnosed.

The “Community Health Challenge” allowed people to donate to charity in return for a complete health check including a blood glucose check. The initiative enabled participants with elevated blood glucose to be referred to their GP for further testing, thereby potentially uncovering cases of silent diabetes that otherwise could have remained undiagnosed for a long time and potentially leading to serious health consequences.¹⁴

Given the substantial and increasing cost burden of diabetes in Australia, we can no longer afford to ignore the importance of diabetes and its devastating impact.¹

So what can be done differently?

Based on “The Community Health Challenge” experience, it can be argued that it’s about time to develop further such initiatives involving communities to enhance individual awareness, engagement and self-management to truly resonate with Australians at risk of developing diabetes, as well as those with the condition needing additional support. These ideally should be implemented under the framework of a national diabetes strategy supported with the appropriate resources and infrastructure needed to deliver improved health outcomes and arrest the increasing burden of diabetes. It really is about time.

CRC’s experienced Medical Affairs team has the expertise to generate RWE data and insights using a variety of methods to maximise therapy value and support Medical Affairs and Market Access related projects.

References

1. Diabetes Australia: National Diabetes Week Campaign. 2019. https://www.itsabouttime.org.au/
2. New National Diabetes Strategy a “once in a decade” chance to refocus Australia’s efforts to fight the biggest threat to our health and productivity. 2015. https://bit.ly/1NtY601
3. Australian Institute of Health and Welfare: Diabetes. 2019. https://bit.ly/2XLyEUi
4. Australian Institute of Health and Welfare: Diabetes snapshot. 2018. https://bit.ly/2TdppuC
5. Australian Bureau of Statistics, Causes of Death, Australia, 2017. https://bit.ly/2VPuwOo
6. Diabetes Australia: Diabetes in Australia. 2018. https://www.diabetesaustralia.com.au/diabetes-in-australia
7. National Health Survey: First Results, 2017-18. https://bit.ly/2LyNHdz
8. Diabetes Australia: What is diabetes https://www.diabetesaustralia.com.au/what-is-diabetes
9. Diabetes Australia: Type 2. https://www.diabetesaustralia.com.au/type-2-diabetes
10. Diabetes: the silent pandemic and its impact on Australia (2012). Baker Heart & Diabetes Institute https://www.baker.edu.au/impact/advocacy/the-silent-pandemic
11. Lee CM et al. The cost of diabetes in adults in Australia. Diabetes Res Clin Pract 2013; 99(3):385-90
12. Carter H. The Economic Consequences of Diabetes: More Than Just a Health Issue. ADEA-QLD Conference 21 April 2018 Presentation. https://www.adea.com.au/wp-content/uploads/2018/04/Hannah-Carter-presentation.pdf
13. Schofield D et al. The Costs of Diabetes Among Australians Aged 45-64 years from 2015 to 2030: Projections of Lost Productive Life Years (PLYs), Lost Personal Income, Lost Taxation Revenue, Extra Welfare Payments And Lost Gross Domestic Product From Health&WealthMOD2030. BMJ Open 2017; 7:e013158.doi:10.1136/bmjopen-2016-013158 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223630/pdf/bmjopen-2016-013158.pdf
14. Challenge uncovers hidden elevated glucose. Australian Journal of Pharmacy. 2019. https://bit.ly/2LA7GbL

Real-world evidence (RWE) is evidence relating to the use and potential benefits and risks of a therapeutic product derived from analysis of real-world data (RWD) from multiple sources. RWD may be derived from sources such as product and disease registries, electronic health records (EHR), insurance claims, pharmacy records, patient generated data (e.g. patient reported outcomes, surveys), social media and sensor outputs from devices.^1,2 RWE is increasingly used to complement data from randomised controlled trials (RCT) and therefore bridge the gap in knowledge between clinical trials and clinical practice. RWE can be used to inform stakeholder understanding of the patient journey, generate meaningful insights into unmet medical needs and enable analysis of the clinical and economic impact of therapies on patients and healthcare systems.³

Types of RWD

Adapted from Swift et al. ²

RWE vs RCT

RCTs are considered the gold standard for approval of new therapies and remain fundamental to evaluating the safety and efficacy of new drugs. However, they are often subject to selection bias whereby patients with chronic illness or other comorbidities and elderly patients may not be represented in clinical trials. For example, less than 5% of adult patients with cancer participate in clinical trials and they tend to be younger, healthier and less diverse than the general population. ⁴ In some cases conventional RCTs alone may not provide sufficient evidence of the relative effectiveness of a therapy to support reimbursement decision-making. A well designed RWE study can supplement the body of clinical evidence to confirm the efficacy and safety of therapies among a broad patient population in routine clinical practice.

Adapted from multiple sources. ^1,3,4

Benefits and Limitations of RWE

The use of RWE in drug development decision-making may enable innovation in clinical programs and trial designs which could potentially reduce the cost of drug development. ² RWE can be used to provide clinicians with insights into how patients will respond to treatment interventions in everyday clinical practice. For example, a large real-world analysis of a monoclonal antibody therapy for treatment of people with psoriasis provided evidence that could not be collected during previous RCTs due to strict inclusion criteria.⁵ The RWE included patients with a range of transition periods (between prior treatment and the new therapy) and those using concomitant treatments and confirmed the safety and effectiveness of the therapy in a diverse range of patients.⁵

RWE can also be leveraged by manufacturers to obtain market access, while payers may use it to substantiate pricing and reimbursement. Therefore, RWE can be beneficial in helping payers and manufacturers to implement performance-based risk-sharing agreements which are increasingly common as many jurisdictions move to implement value based healthcare systems.² However, there are challenges associated with using RWE such as data collection, data quality, developing data analysis methods to mitigate possible biases and protecting patient privacy. These challenges need to be overcome before stakeholders can realise the full potential of RWE to improve clinical practice and help provide safe, effective therapies to the right patients at the right time.

CRC’s experienced Medical Affairs team has the expertise to generate RWE data and insights using a variety of methods to maximise therapy value and support Medical Affairs and Market Access related projects.

References

1. Klonoff D.C. et al. Real-World Evidence Should Be Used in Regulatory Decisions About New Pharmaceutical and Medical Device Products for Diabetes. Available at: https://bit.ly/2KbBOu1
2. Swift B. et al. Innovation at the Intersection of Clinical Trials and Real-World Data Science to Advance Patient Care. 2018. Available at: https://bit.ly/2wQUGWs
3. Anbil P. S. Is There Evidence in Real-World Evidence? 2019. PharmExec. Available at: https://bit.ly/2ULE9h0
4. Gyawali B. et al, Real-World Evidence and Randomized Studies in the Precision Oncology Era: The Right Balance. 2018. ASCO. Available at: https://bit.ly/2I1j3XZ
5. Novartis real-world evidence confirms efficacy and safety benefits of Cosentyx® in daily life for psoriasis patients. 2018. Available at: https://bit.ly/2Cv3LZ0

Drug development has evolved with many healthcare companies now using genetics informed drug development to create targeted and personalised therapies allowing clinicians to treat the underlying causes of a disease. Technological and data analytics advances have enabled researchers to expedite the process of mining drug development leads from vast amounts of genetic data. Genealogy companies are increasingly engaged in partnerships with universities, non-profit organisations and private healthcare companies, indicating the growing importance of genetic data to these companies. Researchers have used insights from genetic data to develop a better understanding of the mechanisms of human disease. However, it remains to be seen if the outputs from these partnerships will result in new therapies being brought to market.

Benefits of Combined Expertise

With the cost of drug development rising and healthcare companies operating in an increasingly competitive market, many are finding innovative methods of drug discovery. For many years, genealogy companies have been collecting genetic data and providing consumers with insights about their biological inheritance. Consumers typically receive information about superficial genetic traits, such as whether your hair is likely to lighten with sun exposure to more serious health related information such as the presence of a genetic mutation associated with disease. Genealogy companies have worked with regulators for permission to disclose information to consumers relating to a limited number of diseases, however strict limits remain on the information they can share due to the complex relationship between the presence of a genetic mutation and the likelihood of developing a disease (1).

Genetic data is highly valuable to researchers using techniques such as genome wide association studies (GWAS) to associate small differences in DNA sequences, called single nucleotide polymorphisms (SNPs), with diseases to find potential drug targets (2). Several genealogy companies in realising the value of large collections of genetic data have developed partnerships with universities, non-profit organisations and pharmaceutical companies to perform GWAS and other studies. For example, just one of the many well-known genealogy companies has lucrative collaborations, which enables multiple healthcare companies to access data from 80% of their over 5 million consumers who have consented to participating in research (3).

Investing in Data 

The average consumer who consents to sharing their data contributes to over 230 studies run by universities, non-profit organisations and healthcare companies (4). Through these collaborative studies researchers are seeking to better understand the genetic basis of a range of diseases including asthma, psychiatric disorders, cancers and Parkinson’s Disease to uncover new drug targets. A recent study has shown that therapies targeting a specific genetic mutation are twice as likely to receive regulatory approval, which is one of the stepping stones required to commercialise new therapies (5). While these collaborative efforts to interrogate vast genetic data sets are yet to result in the discovery of a new therapy, some would say it is only a matter of time before products discovered in this way reach the market.

CRC’s experienced Medical Affairs team has the expertise to understand and utilise insights from genetic data analysis for the purpose of demonstrating therapy value and supporting Medical Affairs related projects.

Reference:

1. Hayden, E. The rise and fall and rise again of 23andMe. 2017. Nature. Available at: https://go.nature.com/2wZ1RdE
2. A better way to find drug targets. 2017. The European Bioinformatics Institute. Available at: https://bit.ly/2GLnHco
3. Molteni, M. 23andme’s pharma deals have been the plan all along. 2018. Wired. Available at: https://bit.ly/2MFYcJF
4. Brodwin, E. DNA-testing companies like 23andMe sell your genetic data to drugmakers and other Silicon Valley startups. 2018. Business Insider. Available at: https://bit.ly/2NbVtsz
5. Ma, Y. Targeted drugs score more wins. 2019. Pharma in focus. Available at: https://bit.ly/2BA70xh

Medical affairs teams have a growing and important role in ensuring pharmaceutical and medical device companies successfully implement strategies to capitalise on digital technologies, advances in big data analytics and the ‘Internet of Medical Things’. Healthcare companies can now access and analyse vast amounts of healthcare data via sources such as wearable medical devices, electronic medical records and healthcare apps. Medical affairs teams equipped with the expertise to access, define, gather and interpret this data can generate valuable insights, thus providing unprecedented opportunities to improve patient outcomes.

Collaborating with Technology Experts

Many big pharma companies realising the growing importance of digital technologies have partnered with or even acquired health technology companies to capitalise on readily available expertise in data collection and analytics. One report listed 56 acquisitions and mergers in the digital healthcare space in 2018 alone, 13 of which had a combined value of $7.6 billion USD (2). One example is the acquisition by a pharmaceutical company of Flatiron Health, a company specialising in oncology specific electronic health record (EHR) software. Through this partnership the pharma company can utilise the technology and data analytics infrastructure needed to generate real-world evidence and in turn accelerate the development of, and access to, new cancer therapies (3).

Medical affairs is typically the function that takes the lead in interpreting data and generating evidence detailing product value for development of strategic communications activities tailored to various stakeholders. Achieving this in the digital age increasingly requires collaborations with data providers and analytics companies to integrate new ways of engaging with patients, monitoring their progress during clinical trials and collecting real-world data at lower cost (1). An example of one such collaboration between a pharmaceutical company and technology giant Apple involved use of the ‘ResearchKit’ app to monitor patients’ progress during a large rheumatoid arthritis trial. Incorporating use of the app enabled the pharma company to gather data on joint pain and fatigue using a mix of surveys and sensor-enabled tests (1).

Communicate Data Insights to Stakeholders

The deluge of health data can present a challenge for stakeholders including healthcare professionals (HCPs) and patients as they seek to understand the value of increasingly complex diagnostic and treatment options. Medical affairs teams with deep product and disease area knowledge and established relationships with key stakeholders are best placed to identify relevant opportunities to use digital solutions to meet stakeholder needs (4). A recent survey of HCPs found that patient outcomes and real-world evidence are among the most important criteria considered when prescribing (5). Both of these criteria are increasingly influenced and enhanced by digital technology. Patients with access to vast amounts of health information are more informed and empowered than ever. Medical affairs teams can employ digital solutions to engage with and enable patients and advocacy groups to play an important role in their care, while also generating valuable insights about how to develop better therapies and other relevant support solutions.

CRC’s experienced Medical Affairs team has the expertise to plan and implement digital collection and analysis of real-world data as part of a strategic medical communications program designed to optimise our clients’ commercial success.

References:

1. Plantevin, L. et al. Reinventing the Role of Medical Affairs. 2017. PharmExec. Available at: https://bit.ly/2fz81dF
2. Comstock J. 56 digital health mergers and acquisitions in 2018. MobiHealthNews. Available at: https://bit.ly/2SZyClY
3. Muoio D. Roche acquires oncology EHR company Flatiron Health for $1.9B. 2018. MobiHealthNews. Available at: https://bit.ly/2Rz9TrY
4. Devoy, M. Digital Health: The Road Ahead for Medical Affairs. 2018. Elevate Magazine. Available at: https://bit.ly/2TILDAt
5. Plantevin, L. et al. Reinventing the Role of Medical Affairs. 2017. Bain & Company. Available at: https://bit.ly/2TGtmUl

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.

The Evidence Gap

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).

Closing the Gap with RWE

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).

RWE in Australia

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.

References:

1. Australian Government Cancer Australia. All cancers in Australia. 2018. Available at: https://bit.ly/2cfR33K
2. Australian Government Dept of Health. Cancer Fact Sheet. 2018. Available at: https://bit.ly/2DJEefs
3. Chatterjee A., et al. Real-world evidence: Driving a new drug-development paradigm in oncology. 2018. McKinsey&Company. Available at: https://mck.co/2KpCtrs
4. Eastman, P. Potential Value of Real-World Evidence in Lung Cancer Care. 2018. Oncology Times. Available at: https://bit.ly/2R5IVmL
5. Real-World Evidence in Oncology. 2018. IQVIA. Available at: https://bit.ly/2Dus9ds
6. US Food and Drug Administration. Framework for Real World Evidence. 2018. Available at: https://bit.ly/2B0i7ze
7. Kim H., et al. A real-world example of coverage with evidence development in Australia – ipilimumab for the treatment of metastatic melanoma. 2018. Journal of Pharmaceutical Policy and Practice