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
|Clinical||EHR data, test results, radiology images, histology, procedures, provider notes, admission/discharge and progress reports|
|Claims Database||Medical claims, prescription claims, other drug and treatment use data|
|Molecular Profiling||Genomic and genetic testing, biomarker status|
|Mobile Health||Data from wearable devices, fitness trackers, health apps measuring activity and body function|
|Environmental||Lifestyle factors (diet, stress), pollutants, infections, other environmental and occupational sources|
|Patient Reported||Patient reported outcomes, surveys, diaries (diet, habits), personal health records, adverse event reporting, quality of life measurements|
|Social Media||Patient communities, Twitter, Facebook, blogs|
|Literature||Disease burden, clinical characteristics, prevalence/incidence, rates of treatment, resource use and costs, disease control, quality of life measures|
Adapted from Swift et al. 2
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.
|Standard of Evidence||Complementary to RCT||Gold standard|
|Patient Population||Large sample size, limited selection, evaluates patients not typically studied in clinical trials||Limited sample size, highly selective, well defined within specific eligibility criteria|
|Treatment Selection||Uncontrolled||Controlled by randomisation|
|Treatment||As in clinical practice||Restricted by the protocol|
|Toxicity||Helps uncover important toxicity signals requiring long term follow up||Only acute and common toxicities are revealed|
|Outcome||Often observed indirectly||Directly observed|
|Cost of Treatment||Observable||Unknown|
|Direct Comparisons||Invalid due to confounding||Valid due to randomisation|
|Approval of New Therapies||Not always suitable for approving interventions but helpful to validate RCT findings||Considered the gold standard for new drug approvals|
Adapted from multiple sources. 1,3,4
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.
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.
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).
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.
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.
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.
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.
© Copyright 2018 Clinical Research Corporation. All Rights Reserved.