Neil Grubert’s Post

The future shape of HTA in Spain, the role of VALTERMED, cross-border collaboration, transparency and reform of the internal reference pricing system—these were among the subjects covered in a recent interview by Diariofarma with César Hernández, Director General of the Common Portfolio of NHS and Pharmacy Services.   Hernández indicated that the long-awaited Royal Decree on HTA will be published before the summer. Asked whether health economic evaluation will be incorporated into therapeutic positioning reports (IPTs), he said: “It is pointless to debate whether economic aspects should be present or not. ... It makes no sense not to take economic aspects into account. Will economic evaluation be incorporated into health technology assessment? Yes. Does every medication have to have an economic evaluation? No. But what is clear is that both economic and non-economic information must be considered to make informed decisions.” He also expressed the view that “there are situations in which an IPT may not be necessary for reimbursement. In any event, assessments should inform decision-making, so they should be timely and useful for the decision.”   In recent evaluations, the Interministerial Drug Pricing Commission (CIPM) has not made use of the VALTERMED platform. Nevertheless, Hernández thinks “VALTERMED is a tremendously useful tool. The thing is that it becomes complex if you want to use it for everything. It is important to limit its use to pricing and reimbursement control and uncertainty management schemes, and in relation to the European Health Data Regulation, the data lake, etc., to make the flow of information compatible, so that it is not excessively time-consuming. It must also be taken into account that the quality of data collection is not comparable to that of a clinical trial and, therefore, the results may be over- or underestimated in relation to efficacy.”   In April 2023, the Spanish Ministry of Health and Portugal’s National Authority of Medicines and Health Products (Infarmed) seemed “to agree on the suitability of a collaboration between the two countries in terms of economic evaluation. Or, at least, in starting conversations in this sense” (tinyurl.com/3r8jwkj3).   Asked for an update, Hernández commented: “We have very good relations with Infarmed and are looking forward to collaborating on concrete projects. We want to extend the cooperation that exists at the level of pricing and reimbursement authorities (NCAPR), which may be the missing link in the system to be effective and coherent, and which so far has not been possible owing to the distribution of competencies between the Member States and the European Commission. We made a lot of progress on this issue during our European Presidency, and I hope that the Belgian Presidency can bring it to a conclusion and establish a stable framework for collaboration that will even allow us to conduct joint negotiations.” #Spain #HTA #drugpricing #VALTERMED #transparency

The “gamble” of early access will be reviewed by France’s National Health Authority (HAS) in early 2025. HAS recognises the value of early access for patients who lack alternative options but notes that “the risk of exposure to ineffective drugs and/or serious adverse events must not be overlooked. In fact, authorising early access to these products without having all the data on clinical benefit is a form of gamble. In the interests of the patient, every effort must therefore be made to ensure that this gamble is as informed as possible at the time it is taken, and that solid data are available as quickly as possible to dispel any uncertainty.” It is striking that HAS repeatedly uses the word “gamble.”   The aim of the review will be “to provide a better definition of the minimum data required for early access authorisation, and to ensure that the Transparency Committee (TC) and the HAS College have access, within a reasonable timeframe, to data that will confirm or refute the clinical benefit of the drug to limit the risks to patients. These conditions will enable HAS to identify genuinely innovative medicines, and conversely to suspend early access for those whose clinical benefit has not been established by the end of this period.”   A working group “will endeavour to better define what constitutes a suitable clinical development plan” for applications submitted before or after marketing authorisation. The analysis will examine:   ● Study design: the circumstances in which indirect comparisons (e.g., network meta-analysis, matched adjusted indirect comparisons) and non-comparative data (observational data without a control group) are acceptable. ● Relevance of PICO criteria: * Is the population evaluated the one for which the clinical benefit is to be established?  * Are the duration of treatment and management methods appropriate?  * Have confirmatory data been established in comparison with at least one clinically relevant comparator (drug or non-drug)? * Are the endpoints (non-exploratory owing to the overall alpha risk management implemented) relevant for judging clinical benefit? What is the appropriate role for intermediate endpoints, composite outcomes, quality of life? ● Reassessment timetable for discontinuation of the “gamble”: what is a “reasonable period” for obtaining confirmatory data?   Based on the working group’s methodological proposals, the TC will propose amendments to the early access doctrine to specify its expectations in terms of the clinical development plan.   Major changes to #earlyaccess could have significant repercussions. In 2023, 70 companies submitted applications for early access for 188 indications. Overall, 93% of indications granted an ASMR of I-IV were the subject of early access applications. For drugs that qualified for early access after marketing authorisation, the average time to routine reimbursement was 141 days, compared with 629 days for other products (tinyurl.com/4wp2bprs). #France

Dan Ollendorffollowing our earlier discussion.

Research conducted by Eli Lilly Australia & New Zealand revealed that Australian medical specialists want faster and more efficient medicine funding processes, as well as greater input to reimbursement decision-making. You can learn more about ‘The Medicines Waiting Room’ research findings in my article for The Mandarin. It was a pleasure to write this piece with insights from leading oncologist Fran Boyle. At this critical juncture for medicines access in Australia, I hope the needs and views of Australian medical specialists are afforded the attention they deserve. My article is part of a Special Report by The Mandarin titled “Australia's innovative medicines system on trial.” You can read it here: https://lnkd.in/gSMYUM-b   #StrongerPBS #HealthcareReform #HTAReview #AustralianHealthcare #AccessToMedicines

Which HTA agencies influence which others—officially or unofficially? On this occasion, I’m hoping that 𝘺𝘰𝘶 might be able to help me by sharing your experience and insights, because information in the public domain is limited.   NICE’s international influence is well supported by anecdotal evidence and the literature. The OHE published an excellent report, “NICE enough? Do NICE’s Decision Outcomes Impact International HTA Decision-making?” (tinyurl.com/yc3dmbv9). Given its longevity and reputation, as well as the fact that its output is in English, the institute’s global reach is not surprising. The existence of NICE International—a division with the explicit mission to forge partnerships with HTA agencies and healthcare systems abroad—is undoubtedly also a significant factor in the organisation’s impact in other countries. Cross-border collaborations, such as the AUS-CAN-NZ-UK Collaboration Arrangement, offer a further international forum for NICE (tinyurl.com/2s372c8u).   Following Brexit, NICE’s formal role in the EU HTA ecosystem has ended—at a time when joint clinical assessment (JCA) will require agencies in the bloc to work together more closely. I’ve heard suggestions that some were not disappointed at NICE’s departure from the EU scene, believing it would strengthen their hand. And yet, NICE’s influence in Europe lingers. It is one of 15 partners in SUSTAIN-HTA, which will support the HTA Coordination Group and the Subgroup on Methodology (tinyurl.com/yfkw5538). Companies’ JCA dossiers will be required to include any HTA reports on their drugs that may have been published in EEA countries, Australia, Canada, the US and the UK—including #NICE, of course (tinyurl.com/4s587f24). And although Germany is widely perceived to have shaped JCA in the image of AMNOG, more and more Member States are following NICE’s lead in embracing cost-effectiveness as a key element of their national HTA activities after JCA—the procedures that will really determine P&R in each country.   What is your experience of which HTA agencies have the most international influence? Is NICE streets ahead of everyone else? How about the SMC? Is the US Institute for Clinical and Economic Review gaining more attention? Is the fact that the EU specifically mentions reports from English-speaking countries a coincidence? Will #IQWiG become more active internationally (tinyurl.com/mw7xtfzf)? Do the #GBA, HAS, #ZIN, #TLV, NCPE or other agencies have influence elsewhere in Europe—and beyond.   I’d be particularly interested to hear your thoughts on patterns of #influence outside of Europe. For example, with the growing importance of HTA in China and Japan, which foreign agencies carry weight in those countries? And who shapes the practice of #HTA in Latin America?   Finally, what is the nature of international influence? Do agencies study individual assessment reports, or are they more likely to follow broad methods and approaches?   Your thoughts would be greatly appreciated.

The EU with its first-rate hospitals and research centres is an attractive environment for clinical trials, offering a fertile ground for medical innovation. Yet, challenges persist, such as a need for more regulatory harmonization with a lack of growth in trial submissions in the last decade and too many small and fragmented clinical trials generating less impactful clinical evidence.   The Accelerating Clinical Trials in the EU initiative, known now as ACT EU, was launched in January 2022 by the European Commission, Heads of Medicines Agencies and EMA for a stronger and more unified European approach to clinical trials, particularly during public health emergencies, to ensure the EU remains a top destination for clinical research.   We agreed priority actions in a multi-annual workplan to achieve this ambitious goal. I can mention, among others:   🔍 ensuring the highest level of transparency by making the data in the Clinical Trials Information System publicly accessible, while protecting personal data and commercially confidential information;   🌍 prioritising more multinational clinical trials in the EU to allow a swift response to public health emergencies;   🤝 creating strategic links and alignment between stakeholder groups such as industry organizations, healthcare professional and patient organizations, academic researchers and funders, and ethics bodies;   📊 facilitating the analysis of clinical trial data based on research priorities for clinical trial analytics;   💡 supporting innovative clinical trial designs and methodologies.   A great overview of the mission and benefits of ACT EU for public health is available in this new scientific article published by Nature Reviews Drug Discovery, where colleagues from EMA contributed with valuable insights. https://lnkd.in/edQExwcE  

Today at Momentum Clinical Research we celebrate the scientists, researchers, healthcare professionals and participants who make clinical trials and medical advancement possible. Chief Medical Officer, Prof Richard Stubbs spoke last week to Radio NZ to discuss the tremendously rewarding work conducted by Momentum staff across the 13 research sites in New Zealand and Australia. "Our staff are doctors and nurses from all around the country who are incredibly enthusiastic and passionate about the work we do. We think what we do is important and will bring forward the day that there will be better medications for a vast majority of conditions." Dr Stubbs also spoke about the prevalence of rare disorders in New Zealand and the multiple barriers to treatment that these patients face including limited access to publicly funded medicine. Listen to the full interview here: https://loom.ly/JSPB0t8 "Clinical trials can provide an opportunity for individuals to gain access to the best available medicines today and potentially to investigational medicines that could prove to be even better. " "Our spread of research sites across NZ and Australia means if there are clinical trials or new medications coming available, then through our network we can take them to where people live. Therefore the opportunity to participate in clinical trials for relatively rare conditions becomes an option." Clinical trials have come a long way since 1774 when James Lind, a ship's surgeon in the British Royal Navy started what is often considered to be the first randomized clinical trial. Lind found a cure for scurvy after carrying out a clinical trial in just 12 people, of whom two received the active treatment of citrus fruit to treat the disease caused by vitamin C deficiency. Happy International Clinical Trials Day from Momentum Clinical Research! #internationalclinicaltrialsday #MomentumClinicalResearch #clinicaltrials #ClinicalTrialNetwork #AustralasiaResearch #NZClinicalTrials #AustraliaClinicalTrials #raredisorders

I am very excited that the study we have been working on for the past few years has been published in Deutsches Ärzteblatt! 🎉 Now both versions (English and German) are finally available online. German 🇩🇪: https://lnkd.in/eZbiJhEm English 🇬🇧: https://lnkd.in/eYzCVqN7 Our AMTS² score is a clinical prioritization tool designed to identify inpatients at high risk of medication harm. 💊 🏥 This approach allows for targeted medication reviews to detect and resolve drug-related problems, focusing on patients who need them most. 🎯 The AMTS² score is particularly valuable in an environment of scarce specialist resources, as is often the case in German hospitals. By implementing this tool, clinical pharmacists can be allocated more efficiently, maximizing their impact on patient safety. 👩🏼⚕️ Many thanks to our study team, all wards and patients involved at Klinikum Fürth and the Bundesministerium für Gesundheit for funding this study! 💚 #MedicationSafety #PatientSafety #DrugSafety FAU Erlangen-Nürnberg

With major reforms to the Spanish access environment expected through legislation in the coming months, what are the government’s priorities? Two key players have recently offered some insights.   Javier Padilla, the Secretary of State for Health, has indicated that the Royal Decree on Health Technology Assessment is likely to be the first legislation to be published. The Ministry of Health recently issued a new “Guide to the Economic Evaluation of Medicines” (tinyurl.com/ytw3tfkc). The usual perspective will be that of the payer. Padilla acknowledged there are circumstances in which the social perspective is relevant but noted that this debate is “academically rich but sterile in reality” because budget impact—a key determinant of price in #Spain —“cannot be done from a social perspective.”   César Hernández, the Director General of the Common Portfolio of SNS Services and Pharmacy, has said that clinical and economic evaluation—along with other factors, such as “transparency and pragmatic, proportionate and viable evidence”—will determine value. He believes it will be “essential to separate evaluation from decision making and ensure that processes are consistent with those of the EU.”   Besides the introduction of the new legislation on #HTA, the government plans to revise the Law of Guarantees and Rational Use of Medicinal Products and Medical Devices. Reform of the country’s internal reference pricing system will be a priority. Padilla has pointed out that the system was designed at a time when drug shortages were not the major issue they are today. Tackling this problem and “protecting against reckless [price] reductions that put the industrial fabric and access at risk” will be critical objectives. The government will also seek to better differentiate medicines, distinguishing between branded and generic drugs in the outpatient setting and biosimilars in hospitals. Pharmacists will be granted increased powers of substitution, in circumstances that have yet to be defined.   Padilla has also commented on the subject of pricing transparency. The government decided not to appeal against two-high profile court cases that required disclosure of confidential discounts for Novartis’ gene therapies Luxturna and Zolgensma (tinyurl.com/ycyxh5z4). The response is likely to be the same in future cases to avoid the “reputational risk for the Ministry of appealing sentences that it is going to lose.” However, Padilla suggested that confidential prices will not be published unless there is an “obligation in judicial terms.” He will work for a common EU position on #transparency.   The government is also keen to support the continued development of innovative therapies—notably, ATMPs—in Spanish hospitals. To that objective, Hernández has argued that uncertainty must be handled differently for academic pharmaceuticals than for industrially produced medicines: “We must be aware of what we are comparing to maintain realistic expectations.” #marketaccess

Re. pharmaceutical pricing transparency landscape in Spain: Seems the Spanish government is for now being realistic with the impact of their decisions and is holding back about making confidential prices public. However, while the government's decision to hold back on disclosing confidential prices may initially seem prudent, it's essential to acknowledge that some of the damage may have already been done. The pharmaceutical industry, despite this temporary reprieve, will remain acutely aware of the potential consequences of these events and the underlying risks associated with (the always recurrent!) policy shifts. While the current stance may alleviate immediate concerns, the reverberations of previous actions linger, impacting both reputation and future strategic considerations for pharma companies. The reluctance to disclose confidential prices, while seemingly beneficial in the short term, fails to address the long-term ramifications and the inherent uncertainty it introduces into the industry landscape.