In recent years there has been a rise in the availability of precision medicines, many of which require use of companion diagnostic tests to determine which patients will respond to the therapy.1 Innovative precision medicines can potentially cure previously untreatable diseases, however, they are expensive and represent a challenge for payers deciding which therapies to fund. Companion diagnostics may help prove the cost effectiveness of therapies along with providing a number of other benefits.
Increasing healthcare costs globally have led to an emphasis on demonstrating both the clinical and economic value of therapies, which requires forward planning from companies seeking reimbursement. Recent European analysis has shown that companion diagnostics represent a small segment of in vitro diagnostics spending and less then 1% of total healthcare expenditure.2 Yet these specialised diagnostic tests represent a way to minimise inefficient use of healthcare resources by identifying sub-populations of patients that are most likely to achieve positive outcomes from a therapy.2
Oncology is a therapeutic area where treatments have become increasingly personalised therefore creating a growing need for companion diagnostics.3 Traditionally, treatment options (including surgery, radiotherapy and chemotherapy) may have been limited resulting in most patients receiving the same or similar treatment based on the type and stage of their cancer.4 This approach achieved varying degrees of success among patients with some being cured of their disease, while others were exposed to harsh side effects with little or no improvement to their health.
In recent years, advancements in cancer biology research have revealed high levels of variation in the genetic mutations that lead to the development of cancer, which could account for the variation in patient response to a therapy. Recently, many drugs, particularly those to treat cancer, have been developed to target specific aspects of the disease. For example, a drug therapy (such as a monoclonal antibody) may bind to a specific biomarker on cancer cells or turn on an aspect of the patient’s immune response. By developing companion diagnostics to identify these specific biomarkers in a patient’s blood or tissue biopsy, the patients most likely to respond to the targeted therapy can be identified.
Companion diagnostics can add value throughout all stages of clinical development of a therapy by providing a mechanism to collect useful data. During the pre-clinical stage, a diagnostic test could be used to assess the likely success of a proposed therapy, thus reducing the chance of incurring substantial costs at the later stages of development.5 As a potential therapy advances through the clinical trial stages, use of a companion diagnostic could facilitate selection of those patients most likely to respond favourably to the drug. By identifying a well-defined patient population, companies could enrol fewer patients and potentially complete clinical studies in a shorter timeframe which could result in reduced costs.3,6
Inclusion of a companion diagnostic has been attributed with taking a therapy from second or third line treatment in the general population to a first line therapy in a sub-population which can lead to increased revenues.3 Personalised medicines may also result in less adverse reactions which may contribute to healthcare savings.4 This precision approach allows companies to collect impactful data that may provide a more attractive package to payers by treating a select patient segment with greater potential to achieve the desired health outcomes.
CRC’s team has a wealth of experience to assist our clients in their Medical Affairs needs throughout the drug development lifecycle.
We have previously reported this year will be big for biosimilars with several therapies on the horizon to challenge some of the biggest biologic brands. 1 The Australian government has put mechanisms in place to increase awareness of and drive uptake of biosimilars. 2 However, government backing and a more affordable price for these therapies does not guarantee their commercial success. Here we discuss how MSLs can contribute to their company’s strategy for maximising uptake of biosimilars.
The science behind both reference brands and biosimilars is complex and healthcare professionals (HCPs) may be more comfortable prescribing and dispensing established brands which have more evidence to support their use in a given patient population. Biosimilar clinical studies vary from traditional studies because they typically include analytical data showing how the structure of the biosimilar compares to the reference drug and how that structure influences the therapy’s function. HCPs may not be familiar with terminology such as bioequivalence and extrapolation across indications, which are commonly used to discuss biosimilars. 3
Therefore, a key activity for MSLs is to educate HCPs about biosimilars along with sharing product specific information. This should help HCPs to understand and embrace the importance of analytical data over traditional clinical study data when discussing biosimilar development. 4 MSLs can be vigilant for potential gaps in HCPs’ knowledge and seek to address their concerns with the aim of helping them become more comfortable prescribing biosimilars to their patients.
Controversy remains around the safety of multiple switches between reference biologics and biosimilars. HCPs may have concerns about changing a successfully established brand for a particular patient and also be more wary of the potential for adverse reactions among patients receiving biosimilars. It is important for MSLs to become aware of these concerns and the potential medico-legal implications from a HCP perspective. This issue is relevant to both clinicians and pharmacists. In Australia, pharmacists have the authority via ‘a-flagging’ to substitute a biosimilar product at the point of dispensing provided the prescriber has not indicated that brand substitution is not permitted.
HCPs may not be convinced of the evidence around new biosimilars, which can result in them waiting to assess their peers’ experience before prescribing. 5 MSLs could address this reluctance in a number of ways for example, by engaging with key opinion leaders (KOLs) from abroad where biosimilars are more established to provide peer to peer education. MSLs could also assist HCPs to become involved with ‘switching studies’ for biosimilars listed on the PBS to provide the opportunity to capture real-world evidence for the use of biosimilars in a specific patient group.
Patients should also be considered as key stakeholders. When gathering intelligence about the competitor landscape, MSLs should seek information about patient support programs and other benefits that competitor companies offer. They can gain these insights not only from HCPs but by engaging directly with patient support groups and patient advocates. By doing this they can become knowledgeable about patients’ needs and assist in establishing improved, if not similar, services to ensure the biosimilar enters the market with maximum opportunity for commercial success.
CRC’s experienced team can provide strategic and forward-thinking Medical Affairs solutions to provide our clients with biosimilars maximum competitive advantage.
Patient reported outcomes and experiences can be an effective and practical means of capturing necessary real-world evidence of the impact of an intervention not available elsewhere. The following case outlines how Australian patient feedback filled an absence of real world evidence required by decision makers in considering the potential reimbursement of a consumable medical device for a specific subpopulation.
A client of CRC had been seeking reimbursement for several years for a consumable medical device under Australian state governments’ medical aids and equipment schemes. The device is for a well-defined post-surgical subgroup in the community and supported by a longstanding body of clinical evidence, as well as reports of improved quality of life (QoL).
A key benefit known anecdotally for years, yet not assessed in a dedicated study is the reduction of hospital days due to complications from the surgery. In addition, the QoL benefits of the device had never be shown among Australians, which was highly relevant to demonstrating need by patients in the local community setting. The absence of both Australian economic and QoL information was a major barrier to progressing reimbursement.
Exacerbating the situation was a silent patient population without a national advocacy voice nor representative bodies in most Australian states. The issue was also too small for national and state healthcare professional groups to address.
It was clear a compelling economic argument based on local evidence was needed to drive a funding decision in the various states.
A VBHC approach would have been ideal to generate real world ‘pay for performance’ data in showing the value of the medical device for this subpopulation. Yet VBHC was not logistically feasible, given the time, budget, resources and stakeholders required. Our client and the affected subpopulation needed a timely practical solution to gather real world evidence that could be shared with state health departments.
Going directly to the source, i.e. the patients themselves, was the only pragmatic solution. Thus, CRC proposed, prepared and implemented a patient survey conducted online and manually to collect the necessary economic and other data that was ‘fit for purpose’. The short simple survey captured patient experiences with and without use of the medical device to understand, in particular, their consumption of healthcare resources post-surgery and QoL.
The survey generated double the number of responders anticipated. Importantly, it clearly showed fewer hospital days due to post-surgery complications for individuals using the device compared with non-users, as well as better quality of life.
Interim survey results have been shared so far with two state health departments who are interested because for the first time they have a reference point from which to verify key data such as hospital days.
A further (unintentional) benefit of the survey is that it has invigorated a patient group previously silent who had given up hope of the possibility of the device ever being funded.
Survey results continue to be collected for which the plan is to share final results with state governments in progressing a funding decision.
The medical science liaison (MSL) role first emerged in response to regulatory changes within the pharmaceutical industry and an increasing need for healthcare companies to build relationships and research collaborations with key opinion leaders (KOLs). With the introduction of increasingly innovative healthcare products, the activities MSLs are engaged in continue to grow as they are required to communicate complex scientific information to, and gather insights from, a broader range of external stakeholders. However, with tightening budgets in the healthcare industry many companies are seeking appropriate metrics to measure the return on investment from this role. How can this be achieved?
The demands of the MSL role are diverse and the activities vary among companies depending on the type of product they are working on and the development stage of the product (i.e. pre-launch or post-launch). These diverse activities are difficult to track, while MSLs often feel company imposed metrics don’t reflect the value they bring to their organisation.1 Some industry representatives advocate for analysis of a combination of both qualitative and quantitative metrics linked to the overarching medical and commercial goals of the business as a useful method for tracking MSL performance.1-3
Quantitative metrics are faster and easier to track and can be valuable to measure, for example, the time MSLs spend in field, the number of KOL interactions or number of new KOL relationships.1 Quantitative metrics often focus on measuring short-term goals such as securing a target number of KOL interactions. However, there is a concern that reaching a target number of KOL interactions may become the priority rather than focusing on achieving quality outcomes from these interactions.2
Activities such as KOL mapping, gathering competitive intelligence and collecting insights during KOL interactions are intangible, therefore, they need to be tracked qualitatively.1 As an example, securing a meeting with a high profile KOL could require more intelligence gathering activities and take a long time to achieve but hold greater value based on the importance of insights they share relative to the medical and commercial goals of the business. So perhaps achieving long-term goals such as this should be given higher value as key performance indicators (KPI) of an MSL’s success.
So, the difficulty is not a lack of metrics, rather it may be in understanding which outcomes will help achieve the medical affairs plan in supporting the commercial goals and establishing KPIs for those outcomes.4 It may appear confusing, yet medical affairs teams are well placed to understand the importance of specific outcomes and their relevance to commercial goals. MSLs should understand the strategic objectives of the company and their own roles in helping grow the business. For example, if the goal is to have the company’s product listed in clinical guidelines, an MSL could demonstrate their value by profiling and engaging with therapeutic area experts who contribute to driving changes to those guidelines. This strategic activity combined with achieving the desired outcome of having the product listed could provide a clear indication of return on investment from MSL activities.
CRC’s experienced team has a wealth of expertise in Medical Affairs across the entire drug development lifecycle. We can provide innovative MSL strategies and assist in implementing them to maximise commercial success.
In a previous blog, we predicted the controversy surrounding biosimilars would be a hot topic in 2018 and this certainly looks to be true.1 Uncertainty around issues such as naming, prescribing and dispensing has hampered uptake of biosimilars in Australia. So, what do the stakeholders involved need to ensure that uptake improves and the potential healthcare savings are realised?
Biosimilars are medicines produced using living cells that are similar but not identical to an approved reference biological. Although there may be slight variations between both products, biosimilars must be sufficiently comparable and provide the same health outcomes as the reference brand. Biosimilars have a shorter timeframe and are less expensive to develop than the reference brand (Figure 1). With biosimilars there is generally a shorter pre-clinical/clinical study process, particularly as the dosage, efficacy and side effects are the same as for the reference brand.2 This can result in a drug that offers the same health outcomes at a price 20-40% lower than the reference drug.2
Figure 1. Reduced cost for production of biosimilars.
Adapted from ‘Biosimilar Development: Incentives and Challenges’. 2
Governments and payers globally are feeling the pressure to fund spiralling healthcare costs and Australia is no exception. In 2017, six of the top ten most expensive drugs for the Pharmaceutical Benefits Scheme (PBS) were biological medicines costing government over $1.25 billion.3 The introduction of biosimilars is expected to deliver significant savings, improve competition and increase access for patients.
In line with realising these benefits, the Australian government has pledged to increase uptake of biosimilars with the introduction of two ‘uptake drivers’.4 The first driver encourages prescribing of biosimilars rather than the reference biologic for treatment naïve patients via several mechanisms. This means doctors are encouraged to prescribe the biosimilar to patients receiving treatment for the first time. The second provides a streamlined approval process for prescribing biosimilars when switching from the originator brand.4
Australia has taken a comparatively pro-substitution approach, for example allowing the “a-flagging” of anti-TNF biosimilars. A-flagged biosimilars can be substituted by pharmacists at the point of dispensing without permission from the prescribing clinician.5 No other regulator currently allows substitution of biosimilars at pharmacy level. The US has a law in place that may allow pharmacy substitution but only for products with ‘interchangeability designation’ which has yet to be granted to any product. To achieve this designation in the US, data must be provided to demonstrate no clinically meaningful differences in safety, purity and potency from the reference product.6
Substitution of biosimilars is a complex and developing area of clinical practice that requires cooperation and communication between the payer, doctors and pharmacists to ensure patient safety. Patients using biological therapies are potentially at risk of immune-based adverse reactions.7 The introduction of biosimilars has brought new concerns associated with switching from reference brand to biosimilar and the potential for multiple switches back and forth.7 However, there is some reassuring data from studies assessing the outcomes associated with switching between therapies, although this data is limited.7 A further concern associated with multiple switches is the difficulty in discovering which medication has caused the reaction. Immune reactions may take some time to become obvious at which point patients could be taking other medications.8
Some doctors have spoken out against a-flagging of biosimilars due to potential unknown risks associated with multiple switches.9 The practice has even been questioned given that decisions on a-flagging are made by the Pharmaceutical Benefits Advisory Committee and not the Therapeutic Goods Administration as the regulator.9 As more a-flagged biosimilars become available, the responsibility for pharmacists to provide upfront counselling to patients will increase. They will need to ensure patients understand the potential risks involved with switching to a new medication and how to accurately report any adverse reactions, otherwise there may be potential medico-legal implications. For their part, patient groups have urged patients to communicate with their healthcare professionals to ensure they receive the most suitable medication, understand any potential risks and know how to accurately report adverse reactions.9-11
CRC’s business model is designed to deliver Medical Affairs solutions that can address external healthcare policy changes and so continue to build value for our clients as regulatory and market access landscapes evolve.
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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