Market Access (MA) is the process that ensures that a new technology gets fast and sustained access into the market at the right price and for the right patients, who would gain a major benefit from it.
So a deep understanding of each of the bolded words is critical to be successful for any market access challenge.
- THE PROCESS
Market access is impacted by both internal and external processes:
0. Innovation/ Discovery process; there is a big difference between bringing to the market a newly developed (invented) medical device and bringing to the market a newly discovered drug (which would cost up to USD 2,8 billions in R&D, according to most recent studies); however, in both scenarios a series of ‘decision gates’ exist in order to guide investment throughout technology development and manage the associated costs of R&D linked to the likelihood of success.
1. Almost every company has its own launch readiness process which involves virtually every function in the new technology launch preparation, including (and further to market access), regulatory, medical, legal, commercial, marketing, finance, public affairs, patient advocacy, communication, etc.; all functions aim to the same objectives: ensure the best access conditions for the new technology and prepare a successful commercial launch.
2. Payers do have processes: at National level — this includes HTA (full or partial), Pricing, Positioning and Reimbursement conditions approval (including Value-Based Pricing where applicable) and at Regional level (Italy, Spain, Sweden among others) as well as atLocal level (Local Health Units), including Drugs and Therapeutics committees. Sub -National bodies will make decisions based on (yearly) budget availability and positioning of the technology (also by adopting Regional Recommendations or restrictive formulary inclusion decisions).
On the other hand, also Market Access needs good processes in place, linking:
- MA Environment Assessment, which includes a. knowledge of healthcare systems in different countries and what their requirements are; b. understanding of disease management and unmet needs; c. understanding of which clinical evidence seems to have mostly impacted in the past; d. reimbursement status of current treatments and existing restrictions.
- Value creation through significant (right end points, right population observed, right comparators, population numbers) clinical data development and Health Economics & Outcomes Research (HEOR) data development.
- Value Identification, on the basis of Randomized Clinical Trials (RCTs) / HEOR data results and of payers/ proxy payers insights (testing and adapting the “Target Product Profile”)
- Value Communication through the Value Proposition & the Value Dossier to be tested and agreed with R&D and business ‘key decision makers’; together with these strategic tools, companies might want to think about developing other supporting tools depicted below:
- Value confirmation/adaptation, through a solid and continuous Real World Evidence data development plan & analysis; a subsequent repositioning/ re-pricing of the product could also be envisioned and planned accordingly.
In general, the MA process within a company needs to balance the input coming from the local country level with the requirements set at global level, which will provide guidance to the clinical development plan (in strict liaison between MA/ HEOR and Medical/ R&D). With this respect, the global value proposition and the global value dossier (key market access deliverables, developed in collaboration with the key country markets, and cross-functionally) must be adapted to specific market access players at national, regional and local level, considering that each healthcare system is unique.
Finally, establish a measurement system to track progress and drive effective corrective actions, when necessary. At the end, the key challenge is linking all these processes together — for payers, R&D, commercial and MA, “to deliver the right technology to the right patient at the right time and at the right price” (quotation from Dr. David Epstein — ex CEO of Novartis Oncology).
2. NEW TECHNOLOGY
The new technology can refer to a new biologic drug, a new chemical entity, a new medical device, a new digital technology (i.e. a mobile app or more evolved digital solutions) or even a new process (e.g., the new gene therapies like CAR-T or genome editing therapies like CRISPR-CAS9) or a combination of all the previous ones.
Among the above mentioned types of new technology, digital technology needs to be clearly addressed: over the last few years we have seen how this technology can positively improve health outcomes in selected patients populations. Furthermore, new technologies such as Blockchain, AI, IoMT (“Internet of Medical Things”), cloud technologies, augmented reality, robotics etc. will have a significant impact on the way business is traditionally done. And, according to Singularity University (CA), it is just the beginning.
With the rapidly evolving MA landscape, we are now on the cusp of a huge acceleration in the use of disruptive tech applications to explore value options, gain strategic advantage and provide truly innovative market access solutions.
As of Today, the use of digital technology has been conservative, mainly focused on customer-facing applications for market access purposes; nonetheless, digital technology has the potential to inform strategy and become an essential enabler in realizing the strategic vision for pharmaceutical, medical devices and biotechnology companies. And, most of all, to transform patients’ lives, who will gain better health, better quality of life and better experiences within the NHS systems.
For example, the new cloud technology provides an improved framework for real-time decision-making in MA. An embedded AI (Artificial Intelligence) is able to identify risks and maximize opportunities at all levels, from assets in preclinical development to country HTA submissions. This facilitates increased collaboration by linking global thinking with affiliate needs and encouraging effective multifunctional dialogue for product assessment, evidence generation planning and HTA submissions preparation.
These technologies can anticipate payer requirements, prioritize resources, plan evidence generation, get a head start on HTA and reimbursement submissions, and provide a useful future data platform.
It is inevitable that new disruptive technologies will be widely used within MA, and used in partnership with payers/ institutions (see as an example the below chart from Forbes, Dec. 16th Article) and third party technology providers.
3. THE RIGHT PATIENTS
Payers want certainty of patient outcomes and predictability of budget impact. So companies need to be able to identify the right patients (sub)population numbers (i.e., the right epidemiology), also working closely with payers and epidemiologists or clinical experts. This is a fundamental part of the equation when companies are negotiating price and access conditions with National and potentially Regional/ Local budget holders, since: Patient Population x Price = Budget Impact.
The more certain the patient population size is, the more confident payers will be in estimating their budget impact, on the basis of the negotiated price. For this reason, early collaboration with payers or independent institutions that would allow conflicts-of-interest-free judgement is critical for later pricing and access conditions negotiations.
When identifying the right patient population it is critical to determine what (sub)population will likely benefit the most from the new technology, in terms of clinical outcomes and/ or overall response rate. Sometimes, biomarkers can play an important role in pre-defining the best population eligible with the new technology and can allow better precision in terms of total budget impact (see examples of ALK+ mutations in NSCLC or FLT3 mutated patients in AML, or BRAF for Sarcoma, BRCA 1/ 2 in Breast/ Ovarian Cancer and many, many more).
Rare diseases technologies (and orphan or ultra-orphan) clearly have smaller eligible patient populations compared to the traditional blockbuster treatments, so while individual patient costs may be higher, overall budget impact to the healthcare system is, in general, lower. In addition, the higher price tag generally includes higher R&D costs, incentives for discoveries in underserved populations, higher risks linked to neglected research outcomes.
However, it needs to be critically thought what price tag should be linked to the orphan/ rare diseases new technology, considering the budget impact awareness of these treatments is getting increasingly higher in the payers’ agenda.
Benefit means improved health outcomes. Surrogate endpoints (PFS, HbA1c, LDLc) have been traditionally considered as valid end points to demonstrate superiority of one technology vs. another. However, payers are increasingly demanding for hard end points to confirm the superiority of one technology versus another in Randomized Clinical Trials (or in RWE studies), mainly looking at Overall Survival, Mortality rates reductions, etc. Composite end points (i.e. MACE reductions + HR-QoL + CV death or hospitalization) and Patient Reported Outcomes (via HR-QoL studies) could also be significant if developed appropriately and with the right approach.
In developing clinical studies (early and late stage) and, in order to build significant payer value, the focus should be put on primary and secondary endpoints that are relevant for payers; these studies should in fact generate meaningful outcomes, that could potentially deliver value to the healthcare system and true added benefit to patients.
Benefit must be always expressed as additional value compared to the Standard of Care (SoC) as identified by the payer, not the company itself. Preferably, it would be expressed in real-life settings, through Pragmatic Studies, to show how the new medicine performs in more naturalistic environments, which reflect the value that will be delivered in real life, although it is not so easy to be done in all disease settings.
Benefit also needs to be considered relative to ‘future’ SoC — new interventions that might change the clinical practice and not licensed yet when a Phase II/III trial is going to be rolled out. This requires careful Phase II/ III design to enable the appropriate indirect treatment comparisons are put in place. In addition, network meta-analyses should be conducted to answer these important questions. Some gaps might be filled up with ad-hoc RWE studies or ad-hoc Phase 3/4 studies that would optimally complement missing data, especially at local country level.
Phase III trials cannot cover every possible option for SoC and, therefore, at local level, the market access plan must consider how the value proposition and value dossier must be adapted to reflect local clinical practice, using also modeling methods or pathways to build the missing evidence, in time for price negotiations.
Benefit may also relate to improvements in Quality of Life (“QoL”). In this case, it is vital to include effective measures such as EQ5D5L (or even better other disease specific Patient Reported Outcomes — PROs — measurement tools) into Phase III clinical trials to collect utilities that can be reflected into cost per QALY analyses or simply demonstrate a much better value in terms of QoL for a patient vs. another technology (think of FGM technologies vs. vs. CGM technologies or SMBG tools for glucose monitoring). Companies may also be able to map utilities from other disease-related QoL instruments into EQ5D5L.
Finally, companies need to clearly identify who will benefit. Will all patients benefit or will some patient sub-groups benefit more than others? Payers will consider these questions in their assessment of benefit for the ‘right’ patients and available budget.
The definition of Value is strictly correlated with the benefit: a generally accepted definition is given by the ratio between Outcomes and Costs. In this respect, I personally believe that patient experience should also be considered and expressed as per below ratio.
Another open point remains linked to the lower part of the ratio: should costs only include direct and indirect costs or should it also include social costs/ avoided costs? What is the added value of a patient “back to working life” thanks to the technology that allowed it? How could a Health Population Based approach improve total costs estimates?
5. FAST ACCESS
Any delay in access has an impact on patients health and potentially life savings drugs/ technologies could not be made available for months after Regulatory Agencies approval, limiting patients options to live longer and better. Furthermore, R&D investments payback could be seriously delayed and the break-even point pushed further down the product life cycle span, significantly deteriorating the profits available for reinvestment in innovative new medicines/ technologies or for remunerating stakeholders of the company.
There is a clear correlation between fast access, patients access to new technologies and company commercial/ financial success.
What does fast access mean? To provide a European definition, Patients W.A.I.T. (Waiting to Access Innovative Treatment) Indicator by EFPIA could be adopted. It basically refers to (see also EFPIA charts below as an example):
- the rate of availability, measured by the number of medicines available to patients. For most countries this is the point at which the product gains access to the reimbursement list;
- the average time between marketing authorization and patient access, measured by the number of days elapsing from the date of EU marketing authorization (or effective marketing authorization in non-EEA countries) to the day of completion of post-marketing authorization administrative processes.
6. SUSTAINED ACCESS
Payers are increasingly removing/ reviewing mature brands reimbursement criteria and prices, especially when cheaper alternative technologies are available, especially genericsor biosimilars (the latter being the object of a separate dissertation in order to qualify the difference between the 2 categories).
In addition, many payer processes involve review of earlier decisions, which means access can change during the life of a product. Market Access is vital throughout the life cycle of the brand, not just at launch.
For many drugs, 85% of their total value is derived from indications and forms not included in the very first marketing authorization; for example, cancer drugs that are developed in multiple disease settings (i.e. for breast cancer from metastatic to adjuvant to neo-adjuvant indication) and/or in multiple tumor types (e.g. trastuzumab, everolimus, bevacizumab, etc.)
Therefore, access for new indications and new forms, including new embedded technologies such as RFID or similar, are vital elements in achieving the total life-time value of a product.
Furthermore, new drugs, especially in cancer, are now approved based on the targeted mutation and not on the indication (e.g. pembrolizumab, larotrectinib), which complicates even more the initial price setting and subsequent reviews.
A complete different discussion should be opened for medical devices, which follow different approval pathways and generally have shorter life spans due to the quick advancement of technologies.
7. THE RIGHT PRICE
Price is generally associated with the perceived added value of a new technology, which should take into account the intrinsic product value, the value for patients, the value for the Health Care system e the value for society. If drugs were to be priced on a cost basis, that should include production costs, the pro-rate of the $2,8bn+ in R&D invested on average per each single molecule making it to the market, plus the amortization costs linked to the drugs that failed during the development phase. In fact, success rate is currently around 13,8% for all drugs; the figure is even higher — 20.9% — if cancer trials are excluded. That is because cancer drugs had the lowest success rate, a mere 3.4% (see for reference to the above numbers: https://cen.acs.org/articles/96/i7/Drug-development-success-rates-higher.html).
Anyway, as per the above, value is first of all the result of the ratio between (Outcomes+Patient Experience)/ Costs and these two dimensions should be considered as the most relevant ones, not just the price.
From the payers’ perspective, there is a need to consider ‘willingness to pay’, which can vary by disease area and perceived unmet medical needs. Also, due to economic pressure, there is increased focus on ‘ability to pay’: there is an increasing need to justify that the benefit really is worth paying for, such as three months extra life in late-stage cancer treatment or a reduction in Hb1c of 0,4%.
Price needs to reflect value. On the one side, it is necessary to understand how healthcare systems value medicines and new developments. Recently the World Economic Forum has developed a framework to assess value called “Value Based Health Care”, whose implementation — at the moment — seems to be too complex and it might take years before becoming a reality (see Figure 1 above and Future Health Index link enclosed: https://www.futurehealthindex.com/2018/01/26/pillars-value-based-healthcare/).
On the other side, the QALY (Quality Adjusted Life Years: https://www.youtube.com/watch?v=3tDXwKVkn68) system is the best way of measuring value for all situations? In reality, it may discriminate against those with late-stage illnesses and poor prognosis — patients with short life expectancy and poor quality of life. So, in some cases the QALY may not be the right tool to use as demonstrated by the UK Government set up of the Cancer Drugs Fund or by the Italian Government that instituted a special Innovation Fund for Cancer Drugs and other Specialty drugs (mainly Hep. C).
Should other models that would grade the benefits of a drug rather than the price be taken into account? Should a systematic approach à-la-Français be adopted, with SMR and ASMR levels (Italy & Germany have adopted a similar approach too but with substantial differences in the way the grading is allocated)? Should the GRADE methodology play a wider role in assessing added value/ benefit of new technologies?
Or should the Multi Criteria Decision Analysis (MCDA) methodology be the best fit to assess value and set the right price? Could this methodology break down silos and holistically look at the total product value and sustainability of the HC system?
How could new drugs be valued at the beginning of their life, when the real value will be realized over their entire life cycle and when cheaper generics and biosimilars continue to deliver that value for more patients at a lower budget impact? The truth is that real price declines over time with inflation, price cuts, price/ volume agreements, payment by results/ outcomes based agreements, pharmaceutical expense capping, tendering, patient access schemes, tiered pricing schemes and so on.
Setting the right price is probably the most complex and controversial topic of all; that is why payers across the globe and innovative companies are fiercely negotiating every cent of value on the table. All parties for the right reasons.
Market access is everyone’s responsibility in each company, throughout the lifecycle of the technology, from early phases until the so called Loss of Exclusivity (LoE).
So, are companies ready for the upcoming and future Market Access challenges?
Copyright © December 2018, Andrea Mantovani