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.
Immuno-oncology therapies are increasingly being hailed as the fourth pillar of cancer treatment alongside surgery, chemotherapy and radiation therapy. Described as the ‘holy grail’ bringing about a ‘new era’ in cancer treatment, in the coming years a deluge of these therapies will move from the ideal treatment setting of clinical trials to enter the marketplace for use in clinical practice. One could argue that only then will we see beyond the ‘hype’ to more fully understand the potential of these therapies to impact patients’ lives.
Immunotherapies are designed to harness the natural tumour killing mechanisms of the patient’s immune system, thus improving the targeted killing of cancer cells. Unlike some other cancer drugs, these therapies tend to be suitable for only a sub-section of patients who can be identified using biomarkers. However, developing and manufacturing immuno-oncology therapies is costly and therefore the end products are expensive. For example, one recently approved checkpoint inhibitor priced at $51.79 USD per milligram can run over $1 million USD per patient per year.1 Another highly anticipated immune system activating therapy (CAR T-cell therapy) has been launched with a price tag of $475,000 USD per treatment.2 Healthcare systems worldwide are expected to fund these therapies but first they must understand the clinical benefits and cost effectiveness. In the case of cancer therapies this means seeking proof as to whether these therapies extend patients’ lives and/or improve their quality of life.
Investigating therapy value
These therapies have been developed following years of innovative research, yet they are often brought to market before there is sufficient evidence that they extend or improve patient’s quality of life. Overall survival remains the most compelling primary endpoint in oncology studies, however achieving this can take several years.3 In the case of potentially lifesaving therapies there is increased urgency and often the ‘hype’ puts pressure on governments to approve and fund these drugs by relying on surrogate endpoints.4 Of course, no payer wants to refuse to fund a drug due to the high cost and as yet uncertain clinical value only to find out the therapy could have saved many lives. However, the flipside is a potentially unfavourable benefit:risk ratio which does little to improve the patient’s prognosis.
Indeed, a recent study of oncology therapies approved by the European Medicines Agency (EMA) found that between 2009-2013 most oncology drugs entered the market without conclusive evidence of benefit to survival or quality of life.5 Furthermore, after a minimum of 3.3 years follow up, only 35 out of 68 cancer indications approved by the EMA had shown a survival or quality of life gain over existing treatments or placebo. For the remaining 33, uncertainty remains over whether the drugs extend survival or improve quality of life.
As oncology research continues to advance, more targeted and personalised therapies will become available and it will inevitably become increasingly difficult for governments to fund these therapies.6 Therefore, governments and payers may need to negotiate new funding mechanisms such as “conditional” funding deals.4 These deals require commitment from companies to provide post-marketing proof that their therapies are performing better than current treatment options and causing minimal toxicity while extending and/or improving patients’ quality of life. This could facilitate manageable funding of expensive therapies to ensure ongoing affordable access to those patients who will truly benefit.
CRC’s experienced Medical Affairs team are well equipped to demonstrate and communicate the value of innovative oncology therapies and develop effective engagement and market access strategies tailored to a client’s needs.
CAR T-cell therapy:
Treatment that attempts to boost the natural ability of T-cells to fight cancer. T-cells are a type of white blood cell and part of the immune system. Researchers take T-cells from the tumour, isolate the T-cells that are most active against the patient’s cancer or modify the genes in them to make them better able to find and destroy cancer cells. Researchers then grow large batches of these T-cells in the lab and they are injected back into the patient.7
Check-point inhibitor therapy:
Therapy that blocks certain proteins made by specific types of immune cells such as T-cells and some cancer cells. These proteins help keep immune responses in check and can keep T-cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T-cells are able to kill cancer cells better. Examples of checkpoint proteins found on T-cells or cancer cells include PD-1/PD-L1 and CTLA-4/B7-1/B7-2.8
Overall survival (OS):
The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. In a clinical trial, measuring the OS is one way to see how well a new treatment works. OS has long been regarded by the oncology community at large, as well as drug regulatory bodies such as the U.S. Food and Drug Administration (FDA), as the gold standard for demonstrating clinical benefit.9
Progression free survival:
The length of time during and after the treatment of a disease, such as cancer, that patient’s live with the disease without it getting worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.10
The healthcare landscape is changing and companies providing products and services to the industry need to evolve to keep up. In the spirit of a New Year almost upon us, CRC has selected what we believe may be hot topics for the pharmaceutical and medical device industries in 2018.
Biosimilars – much ado about nothing?
The pharmaceutical industry is experiencing a second wave of patent expiry and some of the most successful biological drugs may soon have competition from biosimilar products. The Australian government has pledged to drive the uptake of biosimilars and so has implemented the ‘Biosimilar Awareness Initiative’ to support awareness of, and confidence in, the use of biosimilars (1). Furthermore, changes in the way doctors prescribe biosimilars and new pricing mechanisms are planned to take effect in 2018 (2). While the intention is to encourage greater uptake, controversy around biosimilars remains. So what’s fueling this controversy?
In 2017, the first biosimilar product dispensed largely in community pharmacy was listed on the Pharmaceutical Benefits Scheme. The product is eligible for ‘a-flagging’ meaning that, like generics, it could be substituted by the pharmacist at the point of dispensing without input from the prescribing clinician (3, 4). As shown in Table 1, generic medicines are simple molecules identical to the reference product (5), therefore switching from brand to generic products is considered safe. Biosimilars, on the other hand, are complex molecules that cannot be considered identical to the original brand and so switching between brand and biosimilar is causing some concern (5, 6). However, it is recognised that education is key to building confidence in biosimilars, and so for this reason industry representatives raised the alarm when a planned online government education resource for HCPs was cancelled (7). Yet HCPs and consumers need unbiased, consistent, responsive and user-friendly information developed by independent credible sources (4, 6). Indeed, with the introduction of many new biosimilars expected in 2018 and beyond, now is the time for companies to address concerns around potential issues with multiple switches, product interchangeability and other relevant matters that will impact patient care (4, 6). More to come on this topic in a future blog…
Table reproduced from Biosimilars vs Generics (5).
Forging new paths in reimbursement
In a previous blog, we discussed the increasing need to establish new reimbursement pathways for products that do not fit existing funding mechanisms (8). Recently, one company endeavoured to forge a new pathway following multiple rejections by the PBAC. In this case, a proposal was put to government detailing a unique PBS ‘swap out’ deal reported to be successful in another country (9). The deal under consideration by government could see the introduction of a long-term portfolio funding arrangement with the sponsor that has multiple innovative products in their pipeline and an active R&D program. If successful, this innovative funding option could possibly establish a mechanism whereby access to newly approved medicines would be guaranteed for eligible patients. Now that this request has been made, it’s likely we will see more of these types of ‘solutions’ by other companies in 2018.
Regulatory changes for medical devices
Inadequate clinical evidence is said to be the leading cause of rejection of medical device registration submissions by the TGA (10). A recent update of the TGA’s clinical evidence guidelines for medical devices aims to address this issue by detailing how to conduct clinical evaluations and how to present data in a clinical evidence report (10). Furthermore, the European Commission recently introduced a new Medical Devices Regulation (MDR) detailing a number of changes to be implemented over the next three years regarding the registration of medical devices. In keeping with the Australian Regulatory Authority’s policy of harmonisation with European standards, this new framework will likely impact Australian companies (11). Indeed, the impact of these changes may become more evident in 2018 and beyond and so regulatory teams who have been educated on how to implement the changes will likely have a head start over the competition.
CRC’s capability model is designed to deliver strategic and forward-thinking Medical Affairs solutions that can be adapted to external change and so continue to build value for our clients at all stages of the drug development lifecycle.
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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