https://orcid.org/0000-0001-6996-8552
Abstract
Background
As innovative oncology medicines are rapidly developed, there is increasing pressure on payers to offer patients timely access to life-saving therapies. The uncertainty surrounding these therapies when phase III clinical trials are pending has necessitated new, adapted pathways to market access, with timelines that greatly vary by country. Understanding differences between pathways may identify opportunities to expedite patient access universally.
Objectives
To describe early access pathways for new oncology medicines among selected countries with established health technology assessment (HTA) frameworks and publicly funded health systems, with a special focus on real-world evidence (RWE).
Methods
We reviewed the HTA agency websites of the selected OECD countries: National Institute for Health and Care Excellence (NICE) for England and Wales; Haute Autorité de Santé (HAS) for France; IQWiG and G-BA for Germany; Agenzia Italiana del Farmaco (AIFA) for Italy; Pharmaceutical Benefits Advisory Committee (PBAC) for Australia; and CADTH and Institut National d’Excellence en Santé et Services Sociaux (INESSS) for Canada as the primary source of evidence.
Results
Processes for early patient access to innovative oncology therapies varied across selected countries; however, most countries have an established pathway for publicly funded early access (England and Wales, France, Germany, Italy, and Australia). The utilization of RWE to support earlier access (coverage with evidence) also varied by country, with some HTA organizations being actively engaged in these agreements (NICE, AIFA, and HAS) and others having no established processes in place (G-BA and CADTH/INESSS).
Conclusions
This review of early access pathways for novel oncology medicines found substantial variability between countries of interest. Coverage with evidence frameworks may provide a unique opportunity for industry and payers to collaborate on earlier access to innovative cancer therapies with life-saving potential.
Introduction
The global cancer burden is predicted to rise to 28.4 million cases in 2040, a 47% increase from 2020Citation1. Prior to the COVID-19 pandemic, the mortality rate for patients with cancer had been decreasing over timeCitation2; however, COVID-19 has been associated with delays in screening, diagnosis, and treatment, and is therefore expected to negatively impact this positive trendCitation3–5. Prior to 2019, the remarkable improvement in patient outcomes was attributed to innovation.
Oncology is the leading therapeutic area for new medicines, with 100 new treatments expected in the next 5 yearsCitation6. According to a recent market research report, 30 novel active substances (NASs) were launched in 2021Citation7. Many of these therapies were noted as breakthroughs in immuno-oncology and many included precision biomarkers, which are now seen as a standard of care for multiple tumor typesCitation7.
With the ever-increasing rate of innovative technologies coming to market, health systems are looking to implement processes to balance faster patient access with uncertainty from clinical trial data (e.g. single-arm trials or incomplete phase III data). Regulatory agencies in several countries have recently added new pathways to accelerate marketing authorization of innovative therapies (e.g. adaptive licensing or priority reviews) that focus on populations with high unmet needs. As a result, new oncology medicines frequently qualify for these expedited reviews due to the potential life-saving benefits of earlier access for patientsCitation8. The result of expedited regulatory reviews has placed increasing pressure on health technology assessment (HTA) agencies and public payers to manage a high volume of innovative technologies with immature clinical trial data but potentially life-saving benefits. Unfortunately, the availability and timelines for accelerated pathways across countries are highly variable, leading to substantial disparities in how quickly oncology patients can access innovative therapies.
Early access schemes offer a potential solution for drug manufacturers, patients, providers, and the health system. The purpose of these schemes is to decrease the risk for morbidity and/or mortality in high-risk populations and/or provide treatment options for those with a high unmet need. Populations with high risk are often in oncology and/or rare diseases where innovative therapies may significantly impact patient outcomes. Early access schemes do not eliminate the rigorous review of the HTA body, but rather create an opportunity to publicly fund the innovative therapy prior to finalizing the HTA and pricing negotiation processes. The schemes typically involve collecting additional evidence prior to determining a final recommendation.
Real-world evidence (RWE) is derived from real-world data (RWD), such as patient registries or claims data, and is often used to support early access schemes. By implementing a data collection agreement for key outcomes where there is clinical trial uncertainty, decision-makers can better understand the value and benefits of the new therapy, and drug manufacturers can have faster market access, reduced costs for data collection, and provide a strong case for their value proposition when the outcomes achieve their targets.
To address the evidence uncertainty while expediting access, different mechanisms have been implemented in several countries worldwide. Although the net result is earlier access, there is substantial variability across countries in the processes and timelines of these solutions.
The objective of this paper was to describe early access schemes available for new oncology medicines. The HTA agencies from six OECD countries with publicly funded health systems were selected for this review; namely, England and Wales, Germany, France, Italy, Australia, and Canada.
Methods
Evidence sources
To identify the most relevant and up-to-date information for this review, the HTA agency websites of the countries interestCitation9–16 were the primary source of information. To supplement information from these data sources, a targeted literature review of PubMed was conducted between July and August 2022 with key terms on HTA and early access. Finally, a Google search for grey literature and bibliographic review of key papers identified through the targeted review was also conducted. Finally, the information presented in this paper was validated by global colleagues from the jurisdictions of interest to confirm the processes were accurately represented.
Evidence selection
A single reviewer screened the websites and citations from the HTA websites and targeted search results using predefined criteria: country of interest; English language; published within last 5 years (January 2017–August 2022); and specific to market access and oncology.
For each HTA website, details were extracted on key features of early access schemes. While there are also regulatory pathways to expedite marketing authorization and therefore facilitate earlier HTA reviews in the selected countries (e.g. Health Canada priority review, Project Orbis), these were out of scope for this review. The focus of this review was early access schemes or adapted pathways for HTA or funded access, rather than shorter timelines for traditional pathways.
Results
The typical processes for reimbursement of new oncology medicines varied across countries. Several countries utilize a single body to oversee the HTA, price negotiation, and listing agreements (England and Wales, Italy, and Australia). Other countries have a decentralized model with multiple agencies involved in these processes (Germany, France, and Canada). An overview of the standard market access pathways is shown in and Appendix 1.
Table 1. Overview of market access processes by country.
Another key variability is the inclusion of cost-effectiveness thresholds for HTA reviews. For example, the National Institute for Health and Care Excellence (NICE) requires drug manufacturers to provide a cost-effectiveness model with a cost per quality-adjusted life-year (QALY) of £20,000–£30,000 to receive a positive recommendation with exceptions for a substantially higher threshold (10×) for therapies that address severe unmet need criteriaCitation19. In Canada, CADTH stipulates a willingness-to-pay threshold of $50,000 CAD per QALY for both oncology and non-oncology drugs. Although Australia requires a cost-effectiveness model as part of the reimbursement submission, they do not stipulate a threshold; however, recent reviews on oncology therapies have been noted as approximately $50,000–$80,000 per QALYCitation20,Citation21. Meanwhile countries such as France and Germany focus on clinical effectiveness and do not typically require drug manufacturers to submit cost-effectiveness models to inform reimbursement decisions; however, an assessment of cost-effectiveness may still inform the HTA review ().
Early access schemes also varied by country in terms of timing, where expedited access may occur before regulatory approval or pre-/post-HTA review (). In addition, recent literatureCitation22,Citation23 suggests that the timelines for patient access vary by country, providing the impetus for early access schemes. A previously published analysis of data from OECD countries found substantial disparity in time from first global launch to public reimbursement of an innovative drug therapy, with the slowest countries from our review being Canada and Australia, and fastest countries in our review being Germany and the UKCitation22.
Table 2. Pathways for early access by country.
England and Wales
The NICE has implemented processes for expedited access to innovative medicines in England and Wales. The key differences in the expedited processes are the timepoints for implementation (pre- or post-marketing authorization) and which agency conducts the process (regulatory or reimbursement). The main driver for these initiatives is to address the unmet needs of high-risk populations while evidence is collected to support a permanent listing on the public drug plan.
Managed access agreements (MAAs) are time-limited agreements presenting the conditions where patients will receive National Health Service (NHS)-funded treatment and how data will be collected to address any evidentiary uncertaintiesCitation24. There are two dedicated sources of funding for MAAs: the Cancer Drugs Fund (CDF) and the Innovative Medicines Fund. The CDF provides patients with access to new oncology treatments while further evidence is collectedCitation24. To access the CDF, a given drug must first move through the HTA process and receive a recommendation for use in the CDF if program criteria are met. After reaching the pre-specified exit point from the CDF, the drug again enters the HTA process, leveraging the additional evidence gathered.
Any MAAs must be formally agreed upon by the NHS England, NICE, and the manufacturer. If agreement is reached, access will be aligned with the MAA start and end date, and the process for additional data collection will form part of the agreement. If the new treatment is not approved for routine commissioning, there is also potential for a recommendation to approve access within the CDF if the criteria for program entry are met. A recent study reported that 86% of MAAs end in routine reimbursementCitation25 ().
Table 3. Attributes of early access schemes by country.
France
In 2021, France launched their Health Innovation 2030 plan to accelerate patient access to innovative medicines. As part of this plan, a reformed early access scheme called the Autorisation d’Accès Précoce (AAP) was established for severe or rare disease populations with a high unmet need (i.e. no authorized therapeutic alternatives)Citation30. Drug manufacturers may apply to the Haute Autorité de Santé (HAS) for AAP. The regulatory agency, Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM), conducts an assessment of the benefit-to-risk ratio for AAP prior to marketing authorizationCitation31.
Aggregated RWD from French patients is collected by drug manufacturers for the AAP, and the data are also used for HTA reviews. After marketing authorization, in order to receive an AAP designation, HAS must evaluate the following criteria: the patient is affected by a serious, rare, or disabling disease; no appropriate treatment exists; the treatment cannot be delayed; and there is a strong presumption that the product is innovative, particularly when compared to any clinically relevant comparatorCitation30. If an AAP is approved, then drug manufacturers must agree to make the product available within 2 monthsCitation32.
In addition to the AAP, France has two types of compassionate access schemes launched in 2021: the compassionate access authorization (autorisation d’accès compassionnel or AAC) and the compassionate access framework (cadre de prescription compassionnel or CPC)Citation32. For these programs, the ANSM is the decision maker. These processes allow the use of a product that is not necessarily innovative or initially intended to obtain a marketing authorization but meets a therapeutic needCitation32. The AAC replaced the ATU (Autorisation Temporaire d’Utilisation introduced in 1992), and the CPC replaced the RTU (Recommandation Temporaire d’Utilisation launched in 2011)Citation32.
In France, drugs are entirely covered by national health insurance and reimbursed up to a maximum allowable price with a capped sales volume. Drug manufacturers pay annual rebates if total sales exceed the contractCitation33 ().
Germany
The Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte or BfArM) and the Paul Ehrlich Institute (PEI) are regulatory bodies in Germany. A “compassionate use” program was introduced in 2009 where medicines are made available free of charge, prior to marketing authorization, and under specific conditions, such as a seriously debilitating disease or life-threatening disease when the patient cannot be treated satisfactorily with an authorized productCitation34.
Following market authorization, all new therapies are automatically reimbursed with the price set by the manufacturer for the first 6 months. During this time, the HTA takes place and is followed by price negotiation during months 7–12Citation35. Therefore, Germany has been reported to have one of the fastest market access pathways in the worldCitation22. IQWiG and G-BA have strict policies for manufacturer submissions, where they typically only accept RCT evidence including locally relevant comparators. In addition, observational studies, such as RWE studies, are accepted under limited circumstances (e.g. orphan drugs with dramatic effects on clinical or patient-reported outcomes or safety endpoints)Citation35 ().
Italy
In Italy, the Agenzia Italiana del Farmaco (AIFA) is the national authority for regulatory, pricing and reimbursement, and HTA activities. Registries form a central part of the market access negotiation between AIFA and drug manufacturers. Italy provides pathways for pre-regulatory access including compassionate use, rare and severe diseases, and non-repetitive use of advanced therapies. The choice of route depends on the indication, and these pathways can be combined for access to multi-drug treatment regimens. Generally, pre-regulatory early access routes in Italy are the responsibility of the prescribing physician, and are applied for on a single patient request basisCitation36.
In April 2017, the Italian Ministry of Health announced a €1 billion Innovative Drug Fund, with 50% allocated for oncology medicinesCitation37. Starting from 1 January 2022, the two funds for innovative drugs – innovative oncology drugs and innovative non-oncology drugs – were mergedCitation28. Concurrently, AIFA designed an algorithm to assess innovation and designate innovative classes. New medicines can now access the Innovative Drugs Fund for 36 months and immediately be included in regional formulariesCitation38.
Finally, AIFA manages clinical trial uncertainty post-HTA by implementing performance-based agreements utilizing national registry data. In these scenarios, the government supplies RWD from national registries to measure outcomes for the agreements ().
Australia
Starting in 1993, Australia was one of the first countries to use pharmacoeconomic analyses in drug funding decisionsCitation39. The Therapeutic Goods Administration (TGA), offers a provisional pathway for faster market authorization of treatments for serious or life-threatening conditions. For medicines with this provisional approval, the HTA process by the Pharmaceutical Benefits Advisory Committee (PBAC) can then be initiated earlier, potentially expediting patient access to new treatmentsCitation40. Early access is then available for up to 6 years based on preliminary dataCitation41.
Australia also has a Managed Entry Scheme (MES). Although these agreements can be proposed in the first submission, they are typically utilized when there is uncertainty with clinical benefits, a high unmet clinical need, and stalled price negotiationsCitation42. Similar to England and Wales, drug manufacturers are typically responsible for ongoing data collectionCitation42,Citation43 ().
Canada
Canada’s regulatory agency, Health Canada, has a Special Access Program (SAP) for patients with serious or life-threatening conditions when the conventional treatments have failed or are unsuitableCitation44. Similar to the Italian pre-market authorization process, the SAP is initiated by the treating physician on a case-by-case basis. Final decisions to supply the medicine and decisions on payment requirements are made by the manufacturerCitation44.
Canada’s HTA agencies offer priority review processes but, like Germany, do not have a formalized early access program where patients can receive treatment while evidence collection is ongoing (). Nonetheless, innovative MAAs to support timely access to patients, such as performance-based and outcomes-based agreements (OBAs), have been negotiated in Canada; however, the details on these are confidentialCitation45. Canadian stakeholders have commented that the need for innovative agreements is often identified late in the market access pathway, typically post-HTA. Prolonged timelines to bring innovative oncology medicines to Canadian patients compared to other jurisdictions (years versus months) has been a topic of much discussion, where Canada has been ranked 18 of the 20 OECD countries for time to access to oncology drugsCitation46.
Although there is no formal early access scheme in Quebec, the Quebec Life Sciences Strategy, published in 2017, includes an objective to “further integrate innovation into the health and social services network”Citation17 including expedited access to promising new drugs. After the strategy was published, the Institut National d’Excellence en Santé et Services Sociaux (INESSS) began looking at the “promise of therapeutic value” (“promesse de valeur”)Citation29.
Another opportunity for Canadians to access innovative therapies pre-HTA review is through manufacturer-funded Patient Support Programs (PSPs). These programs are similar to compassionate access schemes in other countries that facilitate access during the pre-listing periodCitation47. Additionally, these programs aim to increase the patient’s understanding of their disease and treatment options, improve outcomes, and increase adherence to treatment. The number of PSPs has rapidly increased in recent years, with approximately 175 oncology PSPs now reported in CanadaCitation48,Citation49.
Discussion
Key findings
As innovative oncology medicines are coming to market to address high-risk populations with severe unmet needs, the timeline for patient access is paramount. The challenge for faster reimbursement of these therapies is the uncertainty of the clinical evidence, when in many cases, promising results have been shown in phase II trials, but phase III results still may be another year or two from completion. Therefore, many jurisdictions have created adapted market access pathways for innovative medicines to balance the evidence uncertainty with faster access.
This review showed substantial variability in expedited market access pathways across the countries of interest. The countries included in this review all have some form of expedited regulatory review process for innovative therapies. However, when it comes to expedited access during the HTA stage, the processes, requirements, and timelines vary greatly. A well-established early access scheme linked to the HTA process is the CDF in England and Wales which expedites access with conditional HTA approval for therapies that meet the pre-specified criteria while additional data are collected. France and Italy also have established processes for allowing patient access to innovative treatments while data continue to be collected, to mitigate the risk for payers. In these cases, funding is allocated for patients to access drugs prior to formal price negotiations and listing agreements.
After marketing authorization, only Germany and Canada do not have a formal early access process linked to HTAs. The Germany HTA process is based primarily on clinical trial data, with limited use of RWE, to demonstrate clinical benefit beyond the current standard of care. In Canada, while RWE is accepted, there is no formal process for funding while additional evidence is being collected (such as RWE) to inform listing decisions. In some instances, PSPs have become a means to gaining earlier access for patients; however, these programs are not systematically administered and operate outside the public health system, adding more variation to patient access.
Role for real-world evidence
Early access schemes typically allow for the capture of additional clinical evidence, either clinical trial evidence (e.g. longer follow-up time) or RWE (e.g. evidence derived from health system or claims data). By allowing earlier access, these programs may also incentivize manufacturers to invest in innovation, while at the same time providing opportunities for the health system and society to realize economic gains through potentially reduced healthcare costs and/or increased workforce productivity for patients and carers.
There is a growing interest in utilizing RWE to complement clinical trial data for HTA decisions. The benefits of RWE include (1) longer follow-up period than is typically feasible through clinical trials due to costs and logistics (e.g. long-term safety or survival outcomes); (2) surrogate control arms with RWD for the standard of care that may not have been available when the clinical trial was designed; (3) more diverse patient populations, including underrepresented subpopulations, who may be more likely to receive the medication but were not included in the clinical trials (e.g. seniors, comorbid populations, lower income status, ethnic or gender diversity); (4) characterization of the burden of disease by understanding the incidence and prevalence of the condition in each jurisdiction; and (5) collection of patient-centric outcomes such as patient-reported and caregiver-reported outcomes (e.g. quality of life, indirect costs, and employment absenteeism), which are often not captured in clinical trials.
Given the interest in utilizing RWE for HTA, several guidance documents have recently been published such as the STaRT-RWE template for planning and reporting RWE studiesCitation50; the HARmonized protocol template for enhancing reproducibility for RWE studiesCitation18; and the RWE registry for publishing study protocols a priori to promote transparent reporting of RWECitation26. In addition, other platforms are being launched to help assess new technologies and expedite market access decisionsCitation27,Citation51.
Impact on patient lives
The motivation for early access schemes is compelling: shortening the timelines for oncology patients with high unmet need to gain access to innovative therapies may lead to reduced morbidity and mortalityCitation52,Citation53. Countries with early access schemes (e.g., England and Wales, France, and Italy) provide publicly funded access to new medicines while additional data are being collected to inform the final recommendations. See Appendix 2 for case study examples.
John Stewart, NHS National Director for Specialised Commissioning in England and Wales noted the following for the CDF: “In just over five years, more than 80,000 people have benefitted from earlier access to a range of cancer drugs, with people in England having access to nearly one-third more cancer drugs compared to the European average”Citation54.
Limitations
Of note, this review does not provide a truly global understanding of early access schemes since only a selected group of countries with established HTA processes and publicly funded drug plans were chosen for study. Furthermore, a systematic literature review was not conducted as the most relevant information was thought to be contained on the websites of HTA agencies. Studies identified in the targeted search were not critically appraised for quality, and we did not examine other processes outside of HTAs that may have influenced trends. Further, our study was limited to English language sources only and publications within the last 5 years. In addition, specific comparisons were made between countries, such as differences in the roles of clinical or economic evidence, but not the roles of patient or clinician input. Given the current research objectives and focus on RWE, these limitations are not believed to impact the findings or interpretation but should nonetheless be taken into consideration.
Conclusions
A variety of initiatives are underway to expedite access to innovative oncology therapies. Our review found that countries with funded access pathways post-regulatory approval and pre-HTA decision had the most expedited access among the countries of interest. A common approach to facilitate early access is coverage with evidence development, whereby access is granted while ongoing data are collected to support the final listing recommendation or decision. The utilization of RWE is variable across countries, with only certain countries utilizing this source of evidence. Therefore, early access schemes and coverage with evidence frameworks that leverage RWE present unique opportunities for stakeholders, including drug manufacturers and payers, to collaborate on delivering better outcomes for patients and health systems. The key learnings from this paper may be useful to a variety of global stakeholders to understand how early access schemes have been implemented in other jurisdictions, and to facilitate adoption for countries without an expedited process for patient access to innovative oncology medicines.
Transparency
Declaration of funding
This research received external funding from AbbVie Canada. The design, study conduct, and financial support for the study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication. No honoraria or payments were made for authorship.
Declaration of financial/other relationships
TC and RN are employed by Medlior Health Outcomes Research Ltd., which received funding for the study from AbbVie Canada. AW is employed by 20Sense Corp., and contracted for Medlior Health Outcomes Research Ltd. DT, PRN, and SB are employed by AbbVie Canada, who funded this study.
Author contributions
All study authors participated in the design of this study, interpretation of the results, and development of the manuscript.
Acknowledgements
We would like to thank Tram Pham and Heather Neilson of Medlior Health Outcomes Research Ltd., for medical writing and editorial assistance. We would also like to thank Natalia Wolfram, Katie Mowbray, Virginie Simonet, Luca Pernarella, and Gregory Blanch of the AbbVie Global team for their assistance with the results.
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Appendix 1:
Overview of routine market access pathways
England and Wales
NICE conducts an HTA to determine reimbursement and pricing for selected drugs and devicesCitation9. The NICE appraisal assesses both the clinical and cost effectiveness for new technologies55. If NICE determines a drug should be recommended for use in the public formulary, NICE will negotiate pricing with the manufacturer utilizing the cost-effectiveness evaluation. Unlike other HTA organizations, NICE also has a publicly stated funding limit of £20,000–£30,000 per quality-adjusted life-year (QALY) for most new drugs to be listed on the public formulary56. However, there is a severity modifier, which if met, can increase the funding threshold. NICE appraisal committees have 5 types of recommendations: recommended, optimised, Cancer Drugs Fund, not recommended, and only in research57. NICE has noted that 84% of their recommendations have been positive (recommended, optimised, or recommended for the Cancer Drugs Fund), either in line with the licensed indication or with some modifications57.
France
HAS conducts an HTA on all new drugs typically based on the clinical evidence alone and determines whether new technologies should be recommended for reimbursement [58]. There are certain circumstances where cost-effectiveness is considered; for example, advanced therapy medicinal products (ATMPs), products with a cost exceeding €20 million in the first 2 years, products with an impact on the health system, professional practices, or patient care deliveryCitation59–62. In many cases, new oncology medicines would meet this criteria. In addition, if the drug is recommended, a government pricing committee typically conducts the price negotiation with the drug manufacturer, and health insurers (Union Nationale des Caisses d‘Assurance Maladie – UNCAM) decide list pricing.
Germany
Germany has a unique approach where all new drugs are automatically listed for 1 year after regulatory approval, based on the drug manufacturer list priceCitation63. During this 1-year period, the drug moves through the German reimbursement and price negotiation processes. IQWiG typically conducts an HTA based on clinical evidence for all new drugs, and G-BA decides the level of added benefit and whether to recommend for reimbursement. The exception is for orphan drugs, where G-BA rather than IQWiG conducts the HTA. If the drug is recommended, the German health insurers (GKV-SV) will initiate price negotiations with the manufacturerCitation64.
Italy
AIFA conducts an HTA based on an appraisal of the clinical evidence after marketing authorizationCitation65. If AIFA determines the product should receive a positive recommendation, then they will proceed with price negotiationsCitation33. Italy requires that both a budget impact model and a second economic analysisCitation66 (cost-effectiveness and sustainability of medicinal products) be submitted by the drug manufacturer.
Australia
Australia has a similar process to the other countries of interest, whereby a national HTA body (PBAC) conducts the HTA review and undertakes the price negotiations for recommended therapies. PBAC has also been recommending Risk Share Arrangements in recent years; they not only consider cost effectiveness, but also cost (budget). PBAC does not stipulate a threshold for reimbursement. Historically, a threshold of approximately $50,000 AUD per QALY has been noted; however, in recent reports of PBAC decisions, some higher thresholds were observedCitation18,Citation67,Citation68.
Canada
Canada has 2 HTA bodies: CADTH and INESSS. CADTH conducts HTA reviews for new health technologies and provides reimbursement recommendations to Canada’s federal, provincial, and territorial public drug plans (with the exception of Quebec) to guide their reimbursement decisionsCitation69. Like NICE, CADTH noted a willingness-to-pay threshold in their recommendation reports of $50,000 CAD per QALY for both oncology and non-oncology drugs. For drugs receiving a positive recommendation from CADTH, price negotiations for the Canadian public drug plans are conducted by the pan-Canadian Pharmaceutical Alliance (pCPA). After this stage, the individual federal and provincial drug plans decide whether to list the drug on their drug plan.
INESSS is an independent agency that provides reimbursement recommendations to the Minister of Health and Social Services in the province of Québec concerning the coverage of health technologies by the public drug planCitation70. For drugs receiving a positive recommendation from INESSS, price negotiations may be conducted by the pCPA.
Appendix 2:
Case studies for early access
The following case studies illustrate scenarios and benefits of early access schemes for patients.
Case Study 1: TAGRISSO (osimertinib)
Situation: The early trial results are promising and there is a high unmet need for treatments for the most common cause of cancer death in the UKCitation71. A report from the National Health Service (NHS) in the UK states “In a trial of the drug – the first of its kind – around nine out of ten patients treated, remained alive and disease-free after two years – compared to more than four in ten who hadn’t received the new therapy. Lung cancer is the most common cause of cancer death in the UK, accounting for one in five of all cancer deaths”Citation71.
Scheme details: An early access agreement (prior to going through the CDF) was reached that provided patients with early access on a budget-neutral basis while the HTA was being conducted. As per a report on the scheme “NHS England, NICE and AstraZeneca have reached an agreement to enable early access to osimertinib for early-stage lung cancer patients in England on a budget-neutral basis to the NHS while NICE undertakes its appraisal”Citation71. In addition, this drug had expedited regulatory review under Project Orbis, and the early access agreement was launched on the same day as regulatory approval (e.g., “Day 0”), which meant that patients accessed the treatment as soon as the drug was approvedCitation72.
Notably, this early access agreement was also influenced by the COVID-19 pandemic, with a focus on innovations in cancer care, and “£160 million invested by NHS England in ‘COVID-friendly’ cancer drugs, that treat patients without having such a big impact on their immune system or offer other benefits such as fewer hospital visits”Citation71.
Impact to patients: Around 100 patients had access to osimertinib in 2021, after the regulatory approval and early access scheme were in place on 7 May 2021. A report from the NHS noted that “Around 100 patients in England with a rare form of cancer will initially have access to the drug, called osimertinib, with many more expected to benefit this year”Citation71. The Early Access Agreement to CDF listing was approximately 208 days; therefore, patients had access to therapy 208 days earlier than if it would have gone through the traditional CDF processCitation71,Citation73.
Case Study 2: YERVOY (ipilimumab)
Situation: Ipilimumab is used to treat patients with unresectable or malignant melanoma. Based on promising data in August 2011, TGA in Australia approved market authorization for this medicine. PBAC made a positive recommendation for the listing of ipilimumab on the Pharmaceutical Benefits Scheme (PBS) in November, 2012. Before making a positive recommendation, 2 submissions were made in July 2011 and March 2012, respectivelyCitation74.
Scheme details: To confirm appropriate use, ensure cost-effectiveness, and manage financial risk, PBAC requested a risk-sharing arrangement with the manufacturer. PBAC also requested a system to verify the predicted overall survival advantages of ipilimumab in real-world clinical practice in AustraliaCitation74. As part of this pay-for-performance agreement, the manufacturer was required to rebate the cost of the performance gap between observed and predicted survival benefits. This was the first time PBAC made a recommendation for a listing being subject to RWD collectionCitation74.
Impact to patients: After extended negotiations, ipilimumab was listed (funded) on the PBS in September 2013. For the patients receiving the PBS subsidised ipilimumab in Australia, the 2-year overall survival rate from the first year was estimated to be between 23.9% and 34.2% versus 23.5% reported in the key ipilimumab registrational trialCitation75. Unlike the previous case study, the risk-sharing agreement did not expedite access for patients since it took over a year to receive a positive recommendation and another year before public listing. However, this example illustrates how frameworks for risk-sharing agreements can be established to mitigate uncertainty and risk while enabling earlier access to new treatments.