Francois Maignen: I think that the current system of authorisation, regulation and reimbursement of medicines is very confusing for patients. A lot of products authorised by regulators are subsequently knocked down by HTA bodies. Would it be much more efficient to authorise truly effective / transformative products which would eventually have a much greater probability of being reimbursed by National healthcare systems?
Anja Schiel (NoMA): @Francois, I think that is the very reason why many HTA's have some sort of horizon scanning activities. Identification of truly transformative products is important but also not so easy.
Anja Schiel (NoMA): We have unfortunately created a system in which maintaining uncertainty around the effectiveness actually can help to ask rather unreasonable prices.
Rita Kessler: The European Pharmaceutical legislation is under revision. Which changes would be needed to raise the bar for marketing authorization?
Anja Schiel (NoMA): A lot....
Rita Kessler: Can you be more precise?
Lydie Meheus: Clinical trials are designed by MAHs for registration purposes, but the resulting data should answer both the research questions from regulators and HTA to support decision making. Should parallel consultation, scientific advice for the design of trials not become mandatory?
Anja Schiel (NoMA): It is a very long list of well intended aspects of the old legislation that turned out in the wrong way. I can't highjack the meeting on this topic.
Francois Maignen: I think that one typical example of limitation of the current regulation / reimbursement system lies with orphan products … Between 40 and 60% of orphan products are available in European countries (putting Germany aside). Pharmaceutical companies have used the Orphan Regulation to market expensive products of dubious (incremental) value esp in oncology. I think that we need better, more stringent regulation ...
Anja Schiel (NoMA): Agree with Francois, that is one are where we see the legislation not incentivising the correct use.
Wija Oortwijn (Netherlands): Indeed.
Anja Schiel (NoMA): Maybe the relay isn't working because the focus is not on the same finish line for everyone. Mine would be access for patients to well documented working drugs, I sometimes wonder if that is the same for all Stakeholders in the system.
Anja Schiel (NoMA): UMN and CMA are some of the issues one can discuss the Pharma legislation and be critical to.
Anja Schiel (NoMA): Totally agree with Eric here!
Francois Maignen: There is also probably an important communication issue about the clinical value of new therapies.
Francois Maignen: Currently patients’ leaflets do not contain any information on the benefits of new products for patients in lay language or simple terms i.e., improvement of quality of life or survival.
Francois Maignen: Only a small number of regulators or HTA bodies provide simple assessments of the therapeutic added value of new therapies.
Francois Maignen: The only one which come to my mind is HAS with ASMR.
Anja Schiel (NoMA): Maybe communication on new drugs is left to the industry too much and Regulators and HTA's/Payers need to learn to communicate a lot better. Adjusting expectations could really make discussions less emotional
Francois Maignen: Of note … 75% of new products were considered to have ASMR IV or V by the HAS over the last years.
Francois Maignen: Including an assessment of the added clinical value and its inclusion in the product information (SPC/PL) would be an incentive to develop better products and would help patients and clinicians to make informed decisions.
Rita Kessler: In recent years, number of scientific advice from EMA to companies increased year by year. Did it have an effect on the company’s development plans?
Anja Schiel (NoMA): In line with Rob's comment, scientific advice is given from the Regulators perspective. Only parallel advice discusses the issue with Regulators and HTAs at the table.
Dan Ollendorf: Not sure where this stands at the moment but this is a promising development w/r/t lay language summaries for patients: https://htai.org/wp-content/uploads/2020/10/Project-Summary-Presentation-SIP.pdf
Lydie Meheus: International alignment on the design of clinical trials that ultimately should serve patients https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/ich-guideline-e8-r1-general-considerations-clinical-studies_en.pdf
Anja Schiel (NoMA): 6 drugs in 2 years and 2 devices
Anja Schiel (NoMA): EUnetHTA21 plans
Heidi Livingstone: It's company choice whether to go for Scientific Advice of any sort, but ultimately if the company doesn't collect the right evidence, it's the patients who loose out either in terms of lack of approval or delayed approval. Do you have any thoughts of how to encourage companies to generate more suitable evidence without it being too onerous?
Heidi Livingstone: Dan we're intending to phase in the SIP at NICE with our new methods and processes next year.
Dan Ollendorf: Excellent! (re: SIP)
Anja Schiel (NoMA): The Bar of evidence is different for HTAs because they have a different decision framework. Putting on the market is maybe good enough for Regulators, but it isn't for patients.
Wija Oortwijn (Netherlands): Exactly
Anja Schiel (NoMA): Believing is not the same as knowing. Surrogacy requires believe, hard endpoints are knowledge
Heidi Livingstone: Thanks for the suggestion, Eric
Wija Oortwijn (Netherlands): In the Netherlands, the Dutch Health Care Research is collaborating very closing with our HTA agency as well as health practice - this is now more incentivized via call for topics/priority setting
Wija Oortwijn (Netherlands): Now about 1 year in place
Lisa Hutchinson: The clock stops ticking when a drug is approved, re: incentives to show evidence an agent works (e.g. in clinical practice). The clock should start (not stop) ticking at initial approval and continue with proactive monitoring.
Anja Schiel (NoMA): Correctly described Lisa. As said when you get approved and possibly also reimbursed when there is large uncertainty what incentive is there to get certainty around the effect size, and run the risk to be less effective than originally believed
Eric Low: magnitude of benefit is important but so is the probability of getting the benefit.
Wija Oortwijn (Netherlands): In practice
Eric Low: yes, exactly.
Dan Ollendorf: Completely agree Eric -- per Rob's point just now, it's not average tumor shrinkage, it's in how many patients was this sufficient to relieve symptoms?
Anja Schiel (NoMA): What is the imminent benefit of reducing a tumour when the patient doesn't experience any change in his/her quality of life other than that they got a 'nice message'?
Francois Maignen: I think that the point is not to wait 10 years until we obtain the evidence. The issue is when a regulatory decision is made on a given surrogate endpoint … 5, 10 years down the line, the evidence on clinical endpoint is still not available.
Wija Oortwijn (Netherlands): Patient preferences can be quantified...
Francois Maignen: Several studies on anticancer agents, PFS/OS were published in the BMJ in particular
Lisa Hutchinson: Thanks Anja, agree with your points, Also thumbs up re: comments from Francois.
Eric Low: Patient preferences studies are under used. Patient organisations and medical research charities should invest more in research that captures patient-evidence to Rob's and less on academic vanity projects and research equals hope projects.
Heidi Livingstone: Thanks
Francois Maignen: I agree with Rob concerning post-auth framework.
Anja Schiel (NoMA): Agree with Francois and Lisa.