Canadian Agency For Drugs And Technologies In Health Research Articles

Barriers and facilitators to designing, maintaining, and utilizing rare disease patient registries: a scoping review protocol.

The objectives of this review are to identify barriers/facilitators to designing, maintaining, and utilizing rare disease patient registries (RDPRs); determine whether and how these differ among patient partners, other knowledge users (KUs), and researchers; and chart definitions of rare diseases and RDPRs. RDPRs are vital to improving the understanding of the natural histories and predictors of outcomes for rare diseases, assessing interventions, and identifying potential participants for clinical trials. Currently, however, the functionality of RDPRs is not fully optimized. To improve the quality and functionality of RDPRs, it is important to understand the barriers and/or facilitators involved in their design, maintenance, and utilization; how these might differ among patient partners, other KUs, and researchers; and to delineate the range of definitions for rare diseases and RDPRs. Evidence of any study design or format (including empirical studies, books, manuals, commentaries, editorials, guidance documents, conference abstracts, review documents, and gray literature) referencing barriers/facilitators for designing, maintaining, or utilizing RDPRs will be considered for inclusion. The review will follow the JBI methodology for scoping reviews. We will search health science databases, including the Cochrane Library, Embase, MEDLINE, the JBI EBP Database, and PsycINFO, from inception onwards, as well as gray literature using the Canadian Agency for Drugs and Technologies in Health (CADTH) Grey Matters guidance. Two independent reviewers will screen titles and abstracts and full-text documents, as well as abstract data. Disagreements will be resolved through discussion or with a third reviewer. Evidence will be synthesized descriptively and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRIMSA-ScR). Open Science Framework https://osf.io/mvf9r.

Is Canada Moving towards a More Agile Regulatory Approval and Reimbursement Process with a Shifting Role for Real-World Evidence (RWE) for Oncology Drugs?

Canada is known to have a complex pathway for new drug approval and reimbursement, resulting in delayed access for patients with serious and life-threatening diseases, such as cancer. Several recent publications from key stakeholders, including patients, physicians and policymakers, highlight patient helplessness, physician frustrations and policymakers entangled in a massive network of bureaucracy unable to make headway. Several quantitative and qualitative assessments using time from regulatory approvals to successful reimbursements confirm long review times and high rejection rates for oncology drugs, especially those receiving conditional approvals. A consensus forum of 18 Canadian oncology clinicians recently voiced frustration with the process and inability to deliver guideline-supported efficacious therapies to their patients. This manuscript compares data extracted from publicly available data sources from 2019 to June 2024 to previous publications. Methods: Public databases from Health Canada, the Canadian Agency for Drugs and Technologies in Health (CADTH), which is in the process of changing to Canada's Drug Agency, and the pan-Canadian Pharmaceutical Alliance (pCPA) were reviewed and the data collected were analyzed with descriptive statistics. Results: From the data, three trends emerge, (i) an increasing number of oncology drugs are receiving conditional approvals from Health Canada, (ii) the percentage of conditionally approved oncology drugs receiving positive reimbursement recommendations from CADTH is still low but appears to be improving, but delays in access are now contingent upon pCPA deciding whether to negotiate price and then the duration of any negotiation, and (iii) real-world evidence is no longer part of the decision-making for conditional approvals. A slight increase in the positive endorsement of RWE used to support CADTH recommendations was observed. Conclusions: The lack of timely access to oncology drugs hurts Canadian patients. While a small trend of improvement appears to be emerging, longer-term data collection is required to ensure sustained patient benefits.

A scoping review of the role of managed entry agreements in upcoming drugs for amyotrophic lateral sclerosis: learning from the case of spinal muscular atrophy

Introduction: The therapeutic options for spinal muscular atrophy (SMA) are encouraging. However, there is currently no cure for amyotrophic lateral sclerosis (ALS). The clinical and economic uncertainty surrounding innovative treatments for rare neurodegenerative diseases makes it necessary to understand managed entry agreements (MEAs). The aim of this study was to review whether models of MEAs in SMA could be extrapolated to ALS. Methods: We performed a scoping review with information on MEAs on SMA in Web of Science (WOS), PubMed, Lyfegen Library, the National Institute for Health and Care Excellence (NICE), and the Canadian Agency for Drugs and Technologies in Health (CADTH). Results: We found 45 results in WOS and PubMed. After an initial survey, 10 were reviewed to assess eligibility, and three were selected. We obtained 44 results from Lyfegen Library, and three results each from NICE and CADTH. Conclusion: The main objective of MEAs is to reduce uncertainty in the financing of drugs with a high budgetary impact and clinical concerns, as is the case with drugs for SMA and ALS. While the information available on MEAs in SMA is scarce, some conceptual models are publicly available. MEAs for long-term treatments for SMA could be used for the design of MEAs in ALS because of their similarities in economic and clinical uncertainty.

Development of a Canadian Guidance for Reporting Real-world Evidence for Regulatory and Health-Technology Assessment (HTA) Decision Making

Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making. A partnership between Canadian health system stakeholders, namely Health Canada and Canada's Drug Agency (formerly the Canadian Agency for Drugs and Technologies in Health (CADTH)), was established to develop a guidance for standardization of reporting of RWE for regulatory and HTA decision-making in Canada. In this article, we describe the methods to develop the Guidance for Reporting Real-World Evidence document and checklist for reporting RWE for regulatory and HTA decision-making in Canada. This guidance can be adapted for other jurisdictions and will have future extensions to incorporate emerging issues with RWE and HTA decision-making.

Health Technology Assessment Reports for Non-Oncology Medications in Canada from 2018 to 2022: Methodological Critiques on Manufacturers' Submissions and a Comparison between Manufacturer and Canadian Agency for Drugs and Technologies in Health (CADTH) Analyses.

Identifying key differences between manufacturers' submitted analysis and economic reanalysis by the Canadian Agency for Drugs and Technologies in Health (CADTH) is an important step toward understanding reimbursement recommendations. We compared economic values reported in manufacturers' analysis with the CADTH reanalysis and also assessed methodological critiques. Two reviewers extracted data from the clinical and economic reports in publicly available CADTH reports from 2018 to 2022. We used the Wilcoxon rank-sum test to assess the difference between mean economic values, and the Chi-square test to assess the association between the CADTH critique final recommendations. Of the total submissions, 99.4% included effectiveness critiques, 88.8% included model structure critiques, 69.1% included utility score critiques, and 78.7% included cost critiques. The median incremental cost-utility ratio (ICUR) in the manufacturers' analyses was $138,658/quality-adjusted life-year (QALY), 2.5-fold lower than the CADTH's reanalysis at $380,251/QALY (p<0.001). The median CADTH reanalysis for 3-year budget impact analysis (BIA) was $4,575,102, which was 27% higher than the manufacturers' submitted 3-year BIA (p<0.001). CADTH requested a price reduction for 95% of all submissions, and the median price reduction request was 63.5%. In 2021 and 2022, the willingness-to-pay threshold identified in CADTH reports remained constant at $50,000 per QALY gained for all medications. There was high frequency of CADTH critiques on manufacturers' submissions in all four aspects of economic submissions: effectiveness, cost, utility score and structure. We observed a higher median incremental cost and lower median incremental QALYs in the CADTH reanalysis compared with the manufacturers' submissions. The resulting higher ICUR in the CADTH reanalysis often leads to a recommendation that the manufacturer needs to reduce its price. The 3-year budget impact was higher in the CADTH reanalyses compared with manufacturers' submissions.

Clinical benefit, reimbursement outcomes, and prices of FDA-approved cancer drugs reviewed through Project Orbis in the USA, Canada, England, and Scotland: a retrospective, comparative analysis

Project Orbis is a global initiative that aims to streamline regulatory review processes across international regulators in the USA, Canada, Australia, UK, Israel, Brazil, Singapore, and Switzerland to bring promising cancer drugs to patients earlier. We explored the clinical benefit, time to regulatory approval and health technology assessment recommendations, reimbursement outcomes, and monthly treatment prices of cancer drugs reviewed through this initiative. For this retrospective, comparative analysis, we identified cancer drug approvals reviewed through Project Orbis in the USA, Canada, and the UK between May 1, 2019, and Nov 1, 2023. Approvals of cancer drugs reviewed Project Orbis were extracted from the Food and Drug Administration (FDA) Oncology Centre of Excellence and all other FDA approvals from the Drugs@FDA database. The co-primary outcomes were time of regulatory review, time from regulatory approval to health technology assessment recommendation (England, Scotland, and Canada), reimbursement outcomes, clinical benefit (defined as median gains in progression-free survival and overall survival) between cancer drug approvals reviewed by Project Orbis and other FDA approval processes, and monthly treatment prices. The Wilcoxon rank-sum and Fisher's Exact tests were used to examine statistical significance between approvals reviewed through Project Orbis and other FDA approvals during the same period. Between May 1, 2019 and Nov 1, 2023, 81 (33%) of 244 cancer drugs approved by the FDA were reviewed through Project Orbis. The median overall survival gains were 4·1 months (IQR 3·3-5·1) compared with 2·7 months (2·1-3·9) for other FDA approvals. Similarly, progression-free survival gains were 2·6 months (IQR 1·7-4·9) for Project Orbis compared with 2·6 months (0·6-5·1) for other FDA approvals. Neither overall survival (p=0·11) nor progression-free survival (p=0·44) gains were significantly different between the two cohorts of approvals. Of the 14 UK Medicines and Healthcare products Regulatory Agency (MHRA) approvals reviewed by the Scottish Medicines Consortium (SMC), the agency gave positive recommendations for all 14 (100%). Of the 15 MHRA approvals reviewed by the National Institute for Health and Care Excellence (NICE), the agency gave positive recommendations for six (40%). Of the 49 approvals reviewed by the Canadian Agency for Drugs and Technologies in Health (CADTH), the agency conditionally recommended 44 (90%). The time between regulatory approval to NICE recommendation increased from a median of 137 days (IQR 102-172) in 2021 to 302 days (184-483) in 2023, SMC recommendation increased from 185 days (in 2021 for one drug only) to 368 days (IQR 313-476) in 2023, and CADTH decision increased from 97 days (in 2020 for one drug only) to 202 days (IQR 153-304) in 2023. The median monthly price of approvals reviewed through Project Orbis was US$20 000 per month (IQR 13 000-37 000). Clinical outcomes of Project Orbis were no different than other FDA approvals during the same time, and access, after a successful health technology assessment, was considerably delayed or absent, raising questions about whether Project Orbis participation translates into faster patient access to medicines with high clinical benefit and sustainable costs. Although future challenges might benefit from regulatory harmonisation, the advantages are currently unclear. None.

Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis

Costly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care. We constructed a probabilistic Markov model comparing next generation sequencing (NGS) assay-guided front-line treatment of acalabrutinib versus venetoclax with obinutuzumab to a comparator wherein patients initiate acalabrutinib. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Analyses were conducted from the British Columbia healthcare system perspective, with outcomes discounted at 1.5%. Assay informed treatment for patients with CLL resulted in an incremental cost effectiveness ratio of $18,040 (95% CI $16,491–$19,501) per quality adjusted life-year (QALY) gained. The probability of the NGS guided treatment algorithm being cost effective was 80% at a willingness to pay threshold of $50,000 and a corresponding ICER of $18,040. Assay-guided treatment sequencing adds additional costs to healthcare but may be a cost-effective intervention for adult patients with CLL. Integration of real-world evidence would improve the validity and reliability of model estimated for decision-makers.

HTA67 Assessing Relationships Between the Canadian Agency for Drugs and Technologies in Health (CADTH) Revised ICERs and Unmet Need, Clinical Benefit, Price Reductions, and Listing Negotiation Timelines

HTA67 Assessing Relationships Between the Canadian Agency for Drugs and Technologies in Health (CADTH) Revised ICERs and Unmet Need, Clinical Benefit, Price Reductions, and Listing Negotiation Timelines

Timeliness of Health Technology Assessments and Price Negotiations for Oncology Drugs in Canada.

To evaluate whether time targets for Canadian Agency for Drugs and Technologies in Health (CADTH) reimbursement reviews and pan-Canadian Pharmaceutical Alliance (pCPA) price negotiations are being achieved for oncology drugs. Recommendations, dates of submission and publication, and indications for oncology medicines issued between January 2014 and December 2023 were recorded from CADTH's reimbursement reports webpage. The date any negotiation began and the date it was completed (successfully or not), or when a decision was made not to pursue negotiation was extracted from the pCPA's webpage. The duration of each CADTH review and pCPA negotiation was calculated, together with time between CADTH's recommendation and start of the pCPA negotiation or a decision not to negotiate. Percentages of reviews completed within CADTH's target and of times taken by the pCPA to decide whether to negotiate and by its price negotiations completed within the relevant targets were calculated. CADTH achieved its 270-days target in 88.2% to 100% of reviews issued between 2015 and 2019 but only in 65.9% to 73.1% of reviews issued in the last three years of the decade. CADTH's "typical timeline" of 180 days was achieved in under 40% of reviews issued in 2015 and not attained in any review in 2021, 2022 or 2023. The pCPA's target of 60 days for deciding whether to negotiate was achieved for all recommendations issued in 2014 but dropped below 40% for the last seven years of the decade; its target of 130 days for negotiations was achieved for over 85% of the recommendations in 2014 but decreased to only 14.3% in 2016 and then gradually increased to 61.5% in 2023. CADTH's "typical timeline" and the pCPA's targets were not met sufficiently to be meaningful. Their processes take too long for cancer drugs.

Cost-effectiveness of the top 100 drugs by public spending in Canada, 2015–2021: a repeated cross-sectional study

ObjectivesTo assess the distribution and spending by cost-effectiveness category among those drugs with the highest public spending levels in Canada.DesignRepeated cross-sectional study.SettingThe Canadian provinces of Manitoba, Ontario, New Brunswick, Nova...

An Exploratory Analysis of the Cost-Effectiveness of a Multi-cancer Early Detection Blood Test Compared with Standard of Care Screening in Ontario, Canada.

Determining whether multi-cancer early detection (MCED) tests are cost effective is important in deciding whether they should be included in the clinical path of cancer care, especially for cancers where screening tools do not exist. The main objective of this study is to determine the cost effectiveness of including a MCED screening regimen together with existing provincial screening protocols for selected cancers that are prevalent in Ontario, Canada, among average risk persons aged 50-75 years. The selected cancers include breast, colorectal, lung, esophageal, liver, pancreatic, stomach, and ovarian. Cost effectiveness was estimated from a provincial Ministry of Health perspective. A state-transition Markov model representing the decision path of both the proposed and existing screening strategies along the natural history of the selected types of cancers was implemented. The incremental cost-effectiveness ratio (ICER) was calculated using data from available literature and the guidelines published by the Canadian Agency for Drugs and Technologies in Health (CADTH) for conducting a cost-effectiveness analysis, which included a discount rate of 1.5% applied to all costs and outcomes. Costs were also converted to 2022 Canadian dollars. To test the robustness of the model, both univariate and probabilistic sensitivity analyses were conducted. MCED screening resulted in more diagnosed cases of each type of cancer, even at an earlier stage of disease. This was also associated with fewer related deaths compared with standard of care. Notwithstanding, the analysis revealed that the MCED intervention was not cost effective [ICER: CAD$143,369 per quality-adjusted life year (QALY)], given a willingness to pay (WTP) threshold of $100,000 per QALY. The probabilistic sensitivity analyses revealed that the MCED intervention strategy was preferred to standard of care no more than 2% of the time at this WTP for both males and females. The model was most sensitive to the cost of MCED screening, and the levels of specificity of the MCED and colorectal cancer screening tests. The main contribution of the study is to present and execute a methodological approach that can be adopted to test the cost effectiveness of an MCED tool in the Canadian setting. The model is also sufficiently generic that it could be adapted to other jurisdictions, and with consideration for increasing the WTP threshold beyond the common $100,000 per QALY limit, given the life-threatening nature of cancer, to ensure that MCED interventions are cost-effective.

Risk of sexual transmission of HIV in the context of viral load suppression.

In 2018, the Public Health Agency of Canada (PHAC) published a systematic review to calculate the risk of sexual transmission of human immunodeficiency virus (HIV) in the context of antiretroviral therapy (ART). In 2022, PHAC commissioned the Canadian Agency for Drugs and Technologies in Health (CADTH) to conduct a rapid review of evidence published since 2017. We undertook a meta-analysis of relevant studies from these two reviews. Studies from the rapid review that adequately assessed exposure (HIV viral load) and outcome (HIV seroconversion) were included and assessed for risk of bias (RoB) and certainty of evidence. Results were pooled to estimate the risk of HIV transmission per 100 person-years. Three studies from the rapid review were eligible for inclusion and one was excluded after RoB assessment. In the remaining studies examining risk among people living with HIV who take ART and maintain a suppressed viral load (fewer than 200 copies/mL, measured every 4-6 months), no sexual transmissions of HIV were observed. The pooled incidence estimate based on these studies, and one from the 2018 PHAC review, was zero transmissions/100 person-years (95% CI: 0.00-0.10). No studies in the rapid review provided data on the risk of sexual transmission of HIV in situations of varying levels of viral load. This update highlights the consistency of evidence since the 2018 PHAC review. There remains no evidence of HIV transmission to sexual partners when a person living with HIV is on ART and maintains a suppressed viral load.

Evaluating the impact of novel oncology drug coverage through patient assistance programs in British Columbia (BC), Canada.

13 Background: Despite a universal public healthcare system, Canadian oncology patients often enroll in patient assistance programs (PAPs) through drug manufacturers to access oncology drugs that are awaiting funding decisions by national and provincial regulatory bodies. Our multicenter study evaluated the pharmacoeconomic and clinical impact of PAPs for cancer patients in BC. Methods: Eligible patients were diagnosed with cancer and enrolled in a PAP for an oncology drug between January 1, 2016 - December 31, 2019 in 3 BC centres. Charts were reviewed for treatment details and survival data. We referenced median overall survival (mOS) or median progression-free survival (mPFS) data from phase III trials. mPFS data was used if mOS was unavailable or not statistically significant. For each drug indication, the hazard ratio from trial data was multiplied by the mOS or mPFS of our cohort to estimate the mOS or mPFS if the drug was not received. Life-years gained (LYG) was defined as the difference between the actual mOS or mPFS in our cohort and the estimated mOS or mPFS if the drug was not received. Mean OS was used if median OS was not reached by the cut-off date January 1, 2021. Quality-adjusted life years (QALY) and cost per drug were obtained from the Canadian Agency for Drugs and Technologies in Health (CADTH). QALY gained per drug was calculated as QALY multiplied by LYG. Assuming $100,000 Canadian dollars (CAD) for 1 QALY gained (based on prior studies), the economic value of QALY gained was calculated as $100,000 CAD multiplied by QALY gained per drug. Results: Our cohort consisted of 1025 patients that accessed 40 oncology drugs via PAP. By the cut-off date, 290 patients continued on treatment while 735 had stopped, most often due to disease progression (69%) or toxicity (14%). 74 patients then accessed another drug in their second exposure to PAP, and 5 patients accessed drugs in their third exposure to PAP. Median time from Health Canada approval to public funding was 2.04 years (IQR 1.53 – 2.34). QALY gained per drug ranged from 0.007-2.997 years for OS and 0.001-1.339 years for PFS. This translated to a total of 268.3 QALY gained in OS and 117.6 QALY gained in PFS. In the first exposure group, total economic value gained from PAP was $26,788,512 for those with OS benefits, $11,763,571 for those with PFS benefits, and total drug costs were $94,150,774. In the second exposure group, total economic value gained was $566,253 for those with OS benefits, $947,134 for those with PFS benefits, and total costs were $4,917,017. In the third exposure group, $44,754 total economic value was gained and total costs were $931,207. Conclusions: Nearly $100 million CAD of non-public funding was required to bridge gaps between regulatory approval and public funding. The economic value and QALY gained from PAPs are substantial. Future studies should focus on strategies to optimize the funding process for novel cancer therapies.

MSR28 The Power of One: Examining the Impact of Single Arm Trials on Oncology Drug Approvals by NICE and CADTH

Single-arm trials (SATs) are widely used to evaluate treatments for rare and orphan diseases, and for advanced and refractory cancer where conducting randomized controlled trials is not feasible or ethical. This study aims to evaluate the impact of SATs on treatment recommendations by the National Institute for Health and Care Excellence (NICE) in the UK and the Canadian Agency for Drugs and Technologies in Health (CADTH) in Canada.

HTA43 Do Complexities of Combination Oncology Submissions Impact Reimbursement Outcomes: An Evaluation of Multi-Therapy Oncology Regimens in Canada

The increasing number of oncology combination regimens has highlighted the complexity of multiple manufacturer evaluations. This study aims to assess the dynamics of combination oncology regimen reviews with the Canadian Agency for Drugs and Technologies in Health (CADTH) and the subsequent pricing negotiations through the pan-Canadian Pharmaceutical Alliance (pCPA).

EE262 Use of Single-Arm Trials in Cadth Reviews of Oncology Drugs

Single-arm trials (SAT) have been increasingly used to support oncology reimbursement submissions worldwide. In a previous study, the authors assessed the use of SAT-based oncology technical appraisals by the National Institute for Health and Care Excellence (NICE) from 2017 to 2022, approach to generate comparative evidence, and recommendations from committee reviews. The objective of this study was to assess the use of SATs in Canadian Agency for Drugs and Technologies in Health (CADTH) reviews of oncology drugs.

EE511 Modeling Approaches in the Cost-Effectiveness Analysis of Cancer Treatments: A Review of Submissions Made to the Canadian Agency for Drugs and Technologies in Health

Partitioned Survival Model (PSM) and State Transition Models are the most frequently used approaches to estimate the cost-effectiveness of treatments. However, each of these approaches have their own limitations in their application in oncology. Our objective was to review the reimbursement submissions of oncology treatments made to Canadian Agency for Drugs and Technologies in Health (CADTH) between 2018 and 2022 to examine the modeling approaches considered by manufacturers.

Conditional Funding Recommendations for Drugs in Canada: A Cross-Sectional Analysis.

Before listing by drug plans, new drugs that receive regulatory bodies' approval are assessed by the Health Technology Assessment agencies, including the Canadian Agency for Drugs and Technologies in Health (CADTH). Considering the impact of CADTH recommendations on payers' listing decisions, the growing number of high-cost drugs, and conditional listings, conditional recommendations have increasingly been of interest to the users of CADTH recommendations. This study aims to review the conditional reimbursement recommendations issued by CADTH and explores the reasons for those recommendations. All final drug reimbursement recommendations posted on the CADTH website since 1 January, 2003 were reviewed. Recommendations were included if accepted for review by 1 May, 2021 and completed before 1 January, 2022. The complete records excluding 'requests for advice' were categorized into 'reimburse,' 'do not reimburse,' and 'reimburse with criteria/condition(s)'. The identified variables were extracted and analyzed descriptively. Of the 889 submissions, 785 (88.6%) completed recommendations were consideredrelevant to the study purpose. Of 750 recommendations, excluding 35 (4.5%) 'requests for advice,' 500 (66.6%) were 'reimburse with criteria/condition(s)'. 'Clinical criteria' at 481 (96.2%), 'cost-effectiveness improvement to an acceptable level' at 132 (26.4%), and 'the treatment cost not to exceed the cost of the alternative option(s)' at 118 (23.6%) were the most frequently reported conditions. The most frequent reasons for conditional reimbursement were 'clinical benefit and economic evaluation' at 304 (60.8%). Of conditional recommendations, 468 (93.6%) included more than one reason. CADTH has facilitated patient access to innovative drugs even with limited evidence by conditional recommendations. The clinical criteria are the cornerstone of conditional recommendations. CADTH has developed the assessment process over time.

Access to Neoadjuvant Pertuzumab for HER2 Positive Breast Cancer in Canada: A Dilemma Increasingly Difficult to Explain

The addition of pertuzumab to neoadjuvant trastuzumab and chemotherapy for women with early-stage, high-risk, HER2+ breast cancer has been observed to lead to higher pathologic complete response rates (pCR), and improved event-free survival compared to trastuzumab and chemotherapy alone. Based on available data, neoadjuvant pertuzumab is recommended by ESMO, ASCO, and NICE as well as by a Canadian Consensus Guideline Group. We discuss the implications for Canadian patients with HER2+ early breast cancer due to a second and final negative funding decision by the Canadian Agency for Drugs and Technologies in Health (CADTH) related to neoadjuvant pertuzumab. This decision will have adverse impacts for up to 1 in 6 women receiving neoadjuvant therapy for high-risk HER2+ breast cancer, due to suboptimal pCR rates and higher risks of invasive breast cancer recurrent events, resulting in the need for more toxic adjuvant therapy.

OP49 A Systematic Review Of The Activities Of Early Advice, Early Dialogue, Scientific Advice By HTA Doers

IntroductionThere is a range of activities that health technology assessment (HTA) doers have started to improve the process of generation of required evidence for new technologies, and the alignment of regulatory and reimbursement processes that retard the access to patients to them. Different organizations call those processes early advice, early dialogue, or scientific advice to those activities.MethodsWe performed a systematic review of the activities named scientific advice (SA), early advice (EA) and early dialogue (ED). Major databases and HTA organizations were explored. The protocol and search strategy were published in PROSPERO. The selection of final articles and documents was done in pairs, and when discrepancies were found a third person resolved with the consensus of the others. A matrix was used to define the commonalities and differences of the described processes.ResultsWe initially retrieved 949 documents, after the analysis of duplications and the full text reading of the selected ones, we finally selected 39 documents and described: the type of technologies, the process, the stakeholders, the duration, the costs, and the impact. Big HTA agencies such as the Canadian Agency for Drugs and Technologies in Health (CADTH) or the National Institute for Health and Care Excellence (NICE) included EA or SA among their portfolio of activities as well as networks (European Network for HTA (EUnetHTA) or smaller agencies such as HTA Wales or Basque Office for HTA (Osteba) among others. The type of activity, the process, duration, purpose and costs differ among HTA doers.ConclusionsThere is a need to define what we meant when we are talking about SA, ED, and EA. In fact, regulators used the same processes with different purposes. Our systematic review and the lessons learnt from the European-funded SAFENMEDTECH project will propose a detailed framework that can be useful to better understanding the needs of each of the involved parties and how to make the processes involved more efficient.