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Sentiment,
LTFU?
Sentiment,
Did you put early patients (missing data) into your recent calculations?
____________________________________________________________________________________________
With 331 total patients in the trial minus 243 = 88 patients remaining
So it would appear there were 88 patients that have lived past 36 months thus far.
And are these patients that have determined the 88.2 km derived curve.
____________________________________________________________________________________________
Unmethylated: 162
Methylated: 131
Total: 293
Missing data patients: 38
Flipper44,
you will not believe me but 2 hours ago I was looking for that same GMP report that I had found a few weeks earlier on the web but I had totally forgotten where I had found it. And just now there is your post. Indeed very funny and thank you! It saved me a lot of time.
This is of the GMP report 2017:
Cell and Gene Therapy GMP Manufacturing in the UK: Capability and Capacity Analysis October 2017
https://ct.catapult.org.uk/sites/default/files/publication/GMP%20Manufacturing%20Report%202017%2030_12_17%20FINAL.pdf
5 Future Capacity and Expansion
Phase 1 of Advent Bioservices’ own new facility in Cambridgeshire, is due to be licensed and operational from Q1 2018 and includes two completed suites (185m2 each), comprising B, C and PD/QC labs, offices and storage space. This facility is due to bring to market 199 m2 of cleanroom footprint (including MAL & PAL areas) in its first phase. However, the site has capacity for a further ~7,500 m2 of additional development.
(Under development) Vision Centre A1301 Sawston Bypass Cambridgeshire CB22 3JG
Flipper44,
I think the job posting on Indeed (post 160800 Evaluate 03/04/18) was from a few months earlier.
I see 1 GMP Production Scientist Advent Bioservices Pilar Velasco Sevillano Sept 2017 – Present.
Pilar Velasco Sevillano
GMP Production Scientist
London, Greater London, United Kingdom
“Hi!
I´ve participated in Spain in several clinical trials like a manager manufacturing to producing mesenchymal stem cells and mononuclear cells under GMP conditions, for implantation in hematology patients and like regenerative treatment in patients with acute myocardial infarction. I worked mainly with cell cultures at unit cell therapy, quality control, microbiological control and staining techniques.
Currently, I have started a fabulous project where I am going to be involved in performing dendritic cell culture as a treatment in oncology patients.”
https://www.linkedin.com/in/pilar-velasco-sevillano-22026a55/
https://www.linkedin.com/search/results/people/v2/?facetCurrentCompany=%5B%2218154948%22%5D
So, I think "full migration" to Sawston about March/April 2019.
So, did
1. NICE violate their own rules?
or
2. Did the UK already grant regulatory approval, and the price is known?
or
3. Other?
Flipper44,
IMO 3. Other!
If the timeline is still tracking there is a first Appraisal Committee meeting on 08 November 2018. IMO that is a hugely important date!
DCVax-L for treating newly diagnosed glioblastoma multiforme [ID836]
In development [GID-TA10143] Expected publication date: 01 May 2019
Provisional Schedule
Committee meeting: 1 08 November 2018
https://www.nice.org.uk/guidance/indevelopment/gid-ta10143
Guide to the processes of technology appraisal
2.5.24 An appraisal may begin before UK regulatory approval for the technology has been granted.
2.5.25 For an STA, NICE aims to hold the first Appraisal Committee meeting as soon as possible after the technology gains a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency, or equivalent from the Medicines and Healthcare Products Regulatory Agency. It is therefore essential that the company informs NICE of all developments in the regulatory approval process. This ensures that NICE publishes guidance on the use of the new technology as soon as possible after receipt of the marketing authorisation and/or its introduction into the UK.
https://www.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/NICE-technology-appraisals/technology-appraisal-processes-guide-sept-2014.pdf
EMA
25 January 2018 EMA/630043/2008
Procedural advice on the evaluation of advanced therapy medicinal product in accordance with Article 8 of Regulation (EC) No 1394/2007
1. Introduction
As provided for in the ATMP Regulation (EC) No 1394/2007, the scientific evaluation of Marketing Authorisation Applications (MAAs) for ATMPs is primarily performed by the Committee for Advanced Therapies (CAT).[The CAT prepares a draft opinion on the quality, safety and efficacy of each ATMP subject to marketing authorisation application (MAA) which is sent for final approval to the Committee for Medicinal Products for Human Use (CHMP). The CHMP recommendation is then sent to the European Commission, which adopts a decision binding in all Member States./b
6. Timetable of the assessment:
Once the initial MAA is validated, the EMA starts the procedure at the monthly start date published on the EMA website. The submission deadlines and detailed procedural timetables are published on the EMA website (see, 'submission deadlines and full procedural timetables').
6.1 Standard timetable for the evaluation of an Advanced Therapy Medicinal Product (ATMP) for initial marketing authorisation application under the centralised application
6.2. Accelerated Assessment: The principles for the accelerated assessment procedure in accordance with Article 14(9) of Regulation (EC) 726/2004 also apply for ATMPs as per the “guideline on the Procedure for Accelerated Assessment Pursuant to Article 14 (9) of Regulation (EC) No 726/2004”.
In case of Advanced Therapy Medicinal Product (ATMP)s, the CAT decides on the accelerated assessment request. The timetable will be arranged to include the review by the Committee for Advanced Therapies.
The initial assessment phase will last 120 days similarly to the standard marketing authorisation procedure; the second phase of assessment will last 30 days - the timetable therefore is 120 + 30 days.
5.9 Role of the EMA The EMA ensures that the draft opinion of the CAT is given within 200 days (not including any clockstops for the applicant to provide answers to questions from the CAT and/or CHMP).
In case a medicinal product for human use contains or consists of GMO, the EMA manages the coordination of the consultation with the GMO competent authority during the assessment procedure.
In the case of advanced therapy medicinal products which incorporate medical devices or active implantable medical devices, (“combined ATMPs”), the EMA manages the coordination of the consultation with the Notified Body at the relevant time points of the procedure.
The EMA ensures that the opinion of the CHMP is given within 210 days (not including any clock-stops for the applicant to provide answers to questions from the CAT and/or CHMP).
The EMA Product Team prepares:
• The Committees assessment report on the basis of the CAT (Co-)Rapporteur(s)’ assessment reports ensuring scientific and regulatory consistency;
• The draft and final opinions for transmission by the CAT and final approval by the CHMP, respectively.
The EMA prepares and communicates with the CAT (Co-)Rapporteurs and CHMP coordinators any relevant public information related to the outcome of the assessment of ATMPs and the withdrawal of an application submitted to the EMA.
The EMA transmits the CHMP Opinion to the Commission.
ATMP Advanced therapy medicinal product
CAT Committee for Advanced Therapies
CHMP Committee for Medicinal Products for Human Use
CP Centralized procedure
EMA European Medicines Agency
EU European Union
GMO Genetically modified organisms
MAA Marketing authorization application
NICE National Institute for Health and Care Excellence
STA Single Technology Appraisal
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2018/02/WC500242957.pdf
Handbook about Regulatory Guidelines and Procedures for the Preclinical and Clinical Stages of Advanced Therapy Medicinal Products (ATMPs)
Section IV. – Marketing Authorization.
As stipulated in the ATMP Regulation, marketing authorization for advanced therapies has to be applied for via the centralized procedure (CP) at the EMA. In general, the standard CP practices and requirements apply and that data as outlined in Annex I of Directive 2001/83/EC needs to be submitted in the marketing authorization application (MAA). However, again a few specific modifications/amendments had to be set down to account for the unique nature of ATMPs. For instance, it is not the Committee for Medicinal Products for Human Use (CHMP), but the Committee for Advanced Therapies (CAT) that is primarily responsible for the scientific evaluation of the application for an ATMP. Furthermore, some specific requirements exist for the summary of product characteristics (SmPC) and a modified assessment timetable applies.
It should be pointed out, however, that obtaining marketing authorization does not guarantee immediate access to the European markets. In most European countries, licensed medicinal products also need to undergo national pricing and reimbursement (P&R) procedures (the so-called “fourth hurdle” to market access). In contrast to the harmonized marketing authorization procedures, pricing and reimbursement systems in the EU are purely national responsibilities and requirements can be vastly different. While a detailed description of P&R systems in EU Member States goes beyond the scope of this handbook, it should be pointed out that the first centrally authorized ATMPs have experienced significant difficulties in obtaining reimbursement agreements in a broad range of countries. Further post-authorization clinical trials are often necessary, not only to fulfil obligations of regulatory approvals (e.g. as part of a conditional marketing authorization), but also to guarantee access to the targeted patients across the EU. Therefore, these efforts need to be considered in the investment needed to develop an ATMP.
1. MAA procedure for ATMPs (incl. assessment timetable).
The details of the MAA evaluation procedure specific to ATMPs, the roles of the various agency stakeholders as well as guidance to the applicant are outlined in a procedural guidance document (Procedural advice on the evaluation of ATMPs 2009).
In summary, the MAA of an ATMP is primarily evaluated by two groups – the CAT Rapporteur’s and the CAT Co-Rapporteur’s assessment teams. Each group includes matter experts for the various disciplines (e.g. quality, safety, efficacy, Pharmacovigilance etc.) as well as a CHMP coordinator. The teams are appointed based on the best available expertise for the ATMP under assessment. The CAT (Co-)Rapporteurs and CHMP coordinators jointly draft the assessment reports (AR) to be circulated to all committee members as well as the applicant.
The CAT is responsible for overall scientific assessment of the application, including the drafting of the milestone ARs (e.g. D120 List of Questions, D180 List of Outstanding Issues); however, critical aspects of the MAA are being discussed at the CHMP, and comments from CHMP as well as other involved working parties are being taken into consideration. The outcome of the CAT’s assessment is a draft opinion on the ATMP’s quality, safety and efficacy, which is forwarded to the CHMP. Based on the CAT opinion, the CHMP adopts a final scientific opinion on the granting, variation, suspension or revocation of a marketing authorization. This recommendation is then sent to the European Commission (EC) for a decision binding in all Member States. In case the CHMP disagrees with the CAT’s draft opinion, a clarification meeting will be organized by the EMA in order to resolve any divergences prior to the adoption of the final opinion by CHMP.
Importantly, the assessment of an ATMP marketing authorization application is being assessed according to a specific timetable. Adherence to these preset procedural timelines allows for the proper coordination of the multiple stakeholders and their tasks that are required during the MAA assessment. The timetables including the monthly deadlines for submission, start of procedure as well as other milestones of the CP are published on the EMA’s website under www.ema.europa.eu > Human regulatoy > Pre-authorisation > Submission dates > Timetables > Timetable: Advanced therapy medicinal products – Full application.
http://p-bio.org/wp-content/uploads/2016/06/ATMP-Handbook-Drug-Development-and-Regulation-Bioreg-Project.pdf
Flipper44,
Guide to the processes of technology appraisal
2 September 2014
3.1.22 With the exception of the draft scope, NICE will not make public, or circulate among consultees and commentators any documents for consultation or guidance on a technology until UK regulatory approval has been granted and the technology’s price is known.
https://www.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/NICE-technology-appraisals/technology-appraisal-processes-guide-sept-2014.pdf
Trocprofit,
Your quote:
August has passed, no news.
A Bosch presentation that told us nothing new.
Dr bosch can’t tell us anything new.(dcvax-L trial)
Guide to the methods of technology appraisal 2013:
3 Evidence
3.3 Types of evidence
Unpublished and part-published evidence
3.3.12 To ensure that the appraisal does not miss important relevant evidence, it is important that attempts are made to identify evidence that is not in the public domain. Such evidence includes unpublished clinical trial data and clinical trial data that are in abstract form only or are incomplete. Such information must be critically appraised and, when appropriate, sensitivity analysis conducted to examine the effects of its incorporation or exclusion.
https://www.nice.org.uk/process/pmg9/chapter/evidence
Post 181551 https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142040719
The following information about the cost price of dcvax-l in the context of compassionate use in the UK was found on a blog called "Our brain tumor cocktails and stories".
The information is from 2015 and comes from a blogger Matjaz (30 December 2015) who had contacted the Company. I think this information is interesting in the context of RTT.
NOTE: it's in EUROS and British Pounds Sterling!
https://btcocktails.blogspot.com/2015/10/dcvax.html#comment-form
Matjaz30 December 2015 at 08:34
Please see the answer regarding costs from Ms. Carol Powers (I guess she is reponsible for public/patient relations) at NWBio:
DCVax-L is a labor intensive, custom-made vaccine based on the patient’s unique biomarkers, using the patient’s own dendritic cells. The vaccine is made in a "batch" manufacturing process, meaning the entire course of vaccine doses is manufactured at one time. In addition, DCVax-L must pass strict quality control standards before it can be released. The charges are as follows:
Total cost €53,000 (Euros) for the Tumor Lysate, DCVax Production and first 3 injections
• Deposit of €19,000 (Euros) due at time of Tumor Lysate production
• Balance of €34,000 (Euros) due at time of Leukapheresis processing
· Subsequent injections (injection 4 and following) cost €17,000 (Euros) each, due at the time of injection
• Leukapheresis costs range from $3,500 to $5,000 depending on the apheresis center and if a central line is required
· Initial consultation fee with UK physician £275 - £500 (British Pounds Sterling) * fees vary with the physician
• Shipping fees for tumor tissue, lysate, and DCVax-L are variable based on location but can be in the range of $1,200 to $1,800 or more
· VAT tax 20% - €10,600 (Euros) paid when the first three doses of vaccine are shipped
· Subsequent doses cost €17,000 (Euros) each and the VAT tax is 20% - €3,400 (Euros) paid prior to administration of the vaccine
• Physician’s charge for administering each dose of DCVax-L in the UK £1,125 - £1,500 * (British Pounds Sterling) * fees vary with the physician
American Brain Tumor Association
18 jun. 2018
In this webinar, Dr. Michael Lim MD, Professor of Neurosurgery, Oncology, Otolaryngology, and Radiation Oncology at Johns Hopkins takes a comprehensive look into immunotherapy as a treatment option for brain tumors. Immunotherapy has gained a great deal of attention for many different tumors. Dr. Lim will discuss the state of the field for immunotherapy for GBM and future directions.
Dr. Michael Lim MD, and DCVAX-L trial:
Min.20.09
Quote:
“This is very early on but again very interesting results”
Quote:
“We think that it’s still a very interesting and promising approach”
3.1.15 NICE encourages consultees to make their individual submissions accessible – for example, by putting them on their own websites after they have sent their submission to NICE.
https://www.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/NICE-technology-appraisals/technology-appraisal-processes-guide-sept-2014.pdf
Quote:
________________________________________
Consultation process
The Charity was asked to feed into the appraisal process as a consultee for DCVax®-L. We talked to patients diagnosed with a glioblastoma, carers, as well as patients who have received the treatment and then used our community's views to form The Charity's consultation response.
Those we asked unanimously reported an unmet need of treatments available on the NHS for patients diagnosed with a glioblastoma.
The people we talked to who have already received the treatment emphasised its promising effect on their quality of life.
Many patients noted little or next-to-no side-effects.
Others positively highlighted DCVax®-L as a treatment that works alongside a patient's immune system as opposed to the weakening of it by the current standard of treatment for glioblastomas.
The Charity will now form part of a NICE appraisal committee in early November where researchers, clinicians, patient representatives and relevant bodies will be brought together to discuss the treatment's suitability for uptake.
https://www.thebraintumourcharity.org/media-centre/news/policy-news/brain-tumour-charity-submits-dcvax-l-consultation/
Guide to the processes of technology appraisal.
2 September 2014
https://www.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/NICE-technology-appraisals/technology-appraisal-processes-guide-sept-2014.pdf
Evidence submission from the company
3.2.5 NICE invites the company to provide an evidence submission using a detailed template. The deadline for receipt of the evidence submission is at least 8 weeks from invitation. After receiving this NICE sends it to the ERG for review.
3.2.6 The information needed for the evidence submission is derived from the decision-analytical approach NICE uses to evaluate the clinical and cost effectiveness of health technologies. This approach is outlined in NICE’s Guide to the methods of technology appraisal. Page limits and instructions on the use of appendices are given for the evidence submission. Submission appendices are not normally provided to the Appraisal Committee or published on the NICE website.
3.2.7 If the company plans to submit an economic model, they should inform NICE what software will be used. NICE accepts fully executable economic models using standard software, that is, Excel, DATA/Treeage, R or WinBUGs. If the company plans to submit a model in a non-standard package, it should tell NICE in advance. NICE, in association with the NIHR HTA programme and the ERG, will then investigate whether the requested software is acceptable. When the company submits a fully executable electronic copy of the model, it must give NICE full access to the programming code. Care should be taken to ensure that the submitted versions of the model program and the written content of the evidence submission match.
3.2.8 NICE offers to send the economic model (in its executable form) to consultees and commentators during consultation on the ACD. If the model contains confidential material that the data owner is unwilling to share with consultees and commentators, despite the assurances provided through the signed confidentiality agreements, NICE will ask the company to redact the model if this can be done without severely limiting the model’s function. Consultees and commentators must make requests for a copy of the model in writing. NICE provides the model on the basis
that the consultee or commentator agrees, in writing, to the following conditions of use:
• The economic model and its contents are confidential and are protected by intellectual property rights, which are owned by the relevant company. It cannot be used for any purpose other than to inform the recipient’s understanding of the committee papers. • The economic model cannot be published by consultees or commentators (except by the company who owns the model), in whole or in part, or used to inform the development of other economic models. • The model must not be run for purposes other than to test its reliability.
3.2.9 If the company wishes to include a patient access scheme proposal as part of its submission, specific requirements apply (see section 5 for more information).
3.2.10 If the timelines of the STA are following the anticipated time frame for regulatory approval, the company must notify NICE when it makes a submission for regulatory approval for the technology being appraised. The notification should also specify when an opinion is expected from the Committee for Medicinal Products for Human Use (or equivalent), when it expects to receive regulatory approval, and the expected wording of the marketing authorisation. The company should also state whether they expect the launch date for their technology in the UK to differ from the regulatory approval date. Companies are required to inform NICE immediately if there are changes in the regulatory approval process that will affect the time frame or have implications for the wording of the marketing authorisation.
3.2.11 NICE is unable to comment on submissions during their preparation.
Statements from non-company consultees
3.2.12 NICE invites all non-company consultees to make a submission providing information on the potential clinical and cost effectiveness of a treatment using the appropriate templates available on the NICE website. The submission should reflect the experience of patients, clinicians or commissioners of current standard treatment in the NHS in England and the potential impact of treatment on health-related quality of life. Implementation issues, such as staffing and training requirements, should also be included. Consultees have at least 8 weeks to provide their submission to NICE. After receiving the evidence submissions, NICE sends them to the ERG for information.
3.3 STA evidence review
Initial clarification
3.3.1 After receiving the company’s evidence submission, NICE and the ERG assess whether the submission is complete and whether the decision problem is specified appropriately with reference to the final scope.
3.3.2 If the evidence submission is incomplete or the decision problem is not specified appropriately, NICE consults with the ERG and sends a letter of clarification to the company within 15 working days of receiving the submission. The company has 10 working days from the date of the correspondence to respond. NICE will organise a face-to-face meeting to discuss any issues that cannot be resolved by other means.
3.3.3 If requests for clarification delay the published timelines, NICE informs consultees and commentators, and publishes the reason for the delay on its website.
3.3.4 At the same time as the response to the clarification request the company should review the confidential status of information in its evidence submission before the Appraisal Committee meeting (see sections 3.1.23– 3.1.29 for details on submission of confidential information).
3.3.5 The company should not submit additional evidence during the evidence review phase unless NICE requests or agrees to this in advance.
Terminating an STA
3.3.6 NICE must ensure that the company prepares the best possible evidence submission for the Appraisal Committee. NICE’s technical leads do not validate the submission but they help to clarify substantive issues. If, after all reasonable requests for clarification, NICE is not satisfied that the evidence submission is adequate for the Appraisal Committee to make a decision or if no evidence submission has been received, the Centre Director or Programme Director will recommend to NICE’s Guidance Executive that the STA should be terminated. NICE will return an inadequate evidence submission to the company noting that no submission has been received. NICE will subsequently advise the NHS that the appraisal has been terminated and that NICE is unable to make a recommendation about the use in the NHS of the technology because no evidence submission was received from the company. NICE will also provide an explanation to help the NHS make local decisions on making the technology available.
3.3.7 A terminated appraisal can be restarted if the company indicates that they wish to make a full evidence submission.
Evidence Review Group report
3.3.8 The ERG prepares a report on the clinical and cost effectiveness of the technology in line with NICE’s Guide to the methods of technology appraisal. The report is based on a review of the company’s evidence submission and advice from the ERG’s clinical advisers. The ERG prepares the report in accordance with the NIHR HTA programme quality criteria, the scope of work as identified in the service level agreement between the Department of Health, the NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC) and NICE, and will use an agreed report template. The ERG is responsible for the content and quality of the report.
3.3.9 The ERG critically evaluates the evidence submission. The ERG may suggest to NICE, during initial clarification, that the company should carry out additional analyses. In that case, the company should include full descriptions of any additional analyses as appendices to the original submission. If the ERG, as part of exploratory analyses, amends the company’s model, it will include technical details of these amendments and their impact in the ERG report. If the ERG carries out significant exploratory analyses of the company’s model, which cannot easily be replicated based on the technical details provided in the ERG report, the ERG will provide these analyses to NICE. NICE will make the analyses available to the company at the fact check stage. All other consultees and commentators may request the ERG analyses in writing during the ACD consultation.
3.3.10 NICE sends the ERG report to the company before it is presented to the Appraisal Committee. The company has 5 working days from the date of sending to check that the report (including confidential information provided by the company) does not contain factual errors, for example, errors in the figures, incorrect quotes from the evidence submission or text that does not describe the facts accurately. NICE prepares a document highlighting any factual errors for the Appraisal Committee and publishes the document on its website as part of the committee papers. The company cannot submit additional evidence during the evidence review phase unless NICE has agreed to this before the main evidence submission, or NICE asks for more evidence. The company is also required to check that the ERG has accurately marked confidential information within the report. This again provides an opportunity for the company to reconsider and update the confidential status of information before the Appraisal Committee meeting.
3.3.11 The ERG report is made available to consultees and commentators, and published on the website (confidential information redacted), with either the ACD or the FAD.
Table 3 Expected timelines for the STA process: starting the process and preparing the ERG report*
Weeks (approx.) since process began
Step 1 NICE invites organisations to participate in the STA as consultees or commentators
Week 0
Step 2 NICE receives evidence submissions from consultees
Week 8
Step 3 NICE requests clarification on the evidence submission
Week 10–11
Step 4 NICE invites selected clinical experts, NHS commissioning experts and patient experts to attend the Appraisal Committee meeting and asks them to submit a written statement
Week 10
Step 5 NICE sends the ERG report to the company for fact checking
Week 18
Step 6 Selected clinical experts, NHS commissioning experts and patient experts submit written statements
Week 18
Step 7 NICE compiles the supporting documentation (see section 3.7.3) and sends it to the Appraisal Committee
Week 19
*Timelines may change in response to individual appraisal requirements.
Longfellow95,
Another rejection! Same story and i believe important for the dcvax-l appraisal.
NICE and cost-effectiveness estimate!
Europe’s first allogeneic stem cell therapy rejected by NICE.
20th August 2018
Cost regulators for the NHS in England and Wales have not approved funding for TiGenix and Takeda’s Alofisel - the first allogeneic stem cell therapy to be approved for use across the European Union – for use in Crohn’s patients.
Quote:
“However, in draft guidelines, the National Institute for Health and Care Excellence said Alofisel showed only a modest improvement in the proportion of people with complex perianal fistulas achieving complete remission compared with placebo in one clinical trial.
“Reliable follow-up results are only available for up to one year, so it is unclear how long the treatment benefit will last,” according to the guidelines.
Because of this, cost-effectiveness estimates are “highly uncertain” and the committee was unable to conclude on the most plausible cost-effectiveness estimate, NICE said.”
http://www.pharmatimes.com/news/europes_first_allogeneic_stem_cell_therapy_rejected_by_nice_1249435#.W3rPqkoedz4.linkedin?_lrsc=cea90543-f2de-4205-92eb-2a7b3025dd3e&utm_source=linkedin.com&utm_medium=referral&utm_term=&utm_content=Elevate&utm_campaign=LinkedIn-Elevate
Laser777,
Thank you for that Yescarta update.(and important for the DCVAX-L appraisal!)
Comment of Meindert Boysen, director of the centre for health technology evaluation at NICE.
http://www.irishnews.com/magazine/science/2018/08/28/news/-breakthrough-personalised-cancer-treatment-rejected-for-nhs-use-1418127/
The National Institute for Health and Care Excellence (Nice) published draft guidance stating that axicabtagene ciloleucel, also known as Yescarta, is not recommended for NHS use for patients with aggressive sub-types of non-Hodgkin lymphoma.
Quote:
“But Nice said that there is no direct data to compare it with the current standard treatment of salvage chemotherapy.
It said that cost of axicabtagene ciloleucel was also too high for it to be considered a cost-effective use of NHS resources.
The health body also considered whether the treatment should be made available to patients through the Cancer Drugs Fund, but concluded that the therapy would not be cost-effective under the scheme.
Meindert Boysen, director of the centre for health technology evaluation at Nice, said: “CAR-T is an exciting innovation in very difficult-to-treat cancers, with a promise of cure for some patients.
“We have been working with the companies involved, and with NHS England, with the aim of ensuring that patients in England are among the first to have access to these new treatments in Europe.
“Although promising, there is still much more we need to know about CAR-T, and unfortunately, in this case, we are not able to recommend axicabtagene ciloleucel for use in the NHS in England at the cost per patient set by Kite Pharma.”
Does CAR-T Therapy Have a Payment Problem?
Published: Aug 23, 2018 By Mark Terry
https://www.biospace.com/article/does-car-t-therapy-have-a-payment-problem-/
Linda Powers: We haven't said anything publicly, so umm, stay tuned! Yes, for everybody else - you're a very well-informed shareholder! - the early access to medicine scheme, the EAM scheme, in the UK, is a two-stage process. So we completed stage-one, and that was the PIM designation. It's very British. Promising Innovative Medicine. That was the intensive evaluation of the technology. And the potential benefits of the technology. And the potential toxicity. The second stage. There's a second stage. And the second stage itself has a couple of stages. First you have to go through a pre-submission process. Make submissions. Get evaluated. And you have to get invited to apply for the second stage. Then you, then you apply for the second stage, and that triggers then a multi-month long further process, which principally focuses on manufacturing. Because is you read the criteria, the decision-criteria, on the MHRA website. MHRA is the regulator agency of the UK, like the FDA of the UK. Umm, the decision-making criteria for stage-one are: Is the disease serious? Are the benefits of this technology potentially a breakthrough? And, is the toxicity worth it? The criteria for the second stage are those same three criteria again; and: how good is your manufacturing? Are we satisfied with your manufacturing? And let me tell you, that for us is, a, a massive sweet-spot. Umm, what we had to go through to satisfy the German regulator to get the Hospital Exemption was very heavily focused on the vigor and quality of our manufacturing. So we've been through that drill and aced it. So we're ready for that.
Conference attendee #5: I have a question about... it pertains to the manufacturing. So let's say, your personalized treatments... what is your capacity? How many of those vaccines, with preparation can you do? And what's your time? (mumbling)
Linda Powers: Yeah. We talk about this. Yeah, we talk about it all the time, because if this technology continues to perform in the way it has been so far and if it's going to applicable to most solid tumor cancers, you're talking about, not 10s of thousands of patients, you're talking of 100s and 100s of thousands of patients for whom it could be a fit. Umm, today the process, umm, the process is to, for the first product, DCVax-L, it's a manual process. For DCVax Direct, it's already partially-automated, the automation system. The answer can only be automation. Right? But, from a business standpoint, there's a point in which the lines cross. Right. We want to get to market and get the product to patients, as quickly as possible. Right, so we're going to do that the way that we're making it now. But, we're busily working, as is anyone who thinks about the future with a cell-therapy product, about end-to-end automation. And one of things about end-to-end automation is, is that it's both a capacity issue, a scale issue, because once you're fully automated in the end, you can virtually treat any number of patients. The other thing is, what people don't often realize is, it's going to further revolutionize your product economics. Why? Because when you make it by hand and there are steps that are open to the air, the whole facility has to be sterile, like a semi-conductor facility. It's massively capital intensive. And that's the biggest part of the finished cost of goods, is those indirect cost of that clean room infrastructure. Once it is automated end-to-end, that all goes out of the equation, because you just have rows and rows of these machines in a warehouse space. So you couple that with the batch manufacturing, and it's a step-change in terms of further enhancement of the economics. And so, everyone is busily working on automation. Umm, we think that's a couple-of-year process from where we are today. And we're working from some of the biggest and the best from all over the world.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=109058160
Aug 14,
Nicola Ambler
PREPARING FOR COMMERCIALISATION WITH THE RIGHT CDMO.
AN INTERVIEW WITH J. KELLY GANJEI, CEO AND CHAIRMAN OF THE BOARD, COGNATE BIOSERVICES, INC
Quote:
“We have several big things in the works that will address multiple aspects of product development and manufacturing that I wish I could discuss at the moment but can’t. All I can say is please stay tuned.”
https://www.phacilitate.co.uk/article/preparing-commercialisation-right-cdmo
Pairofoldsocks,
Susan Bayh, wife of former Gov. Evan Bayh, underwent surgery end May 2018 to remove a brain tumor.
That is three months ago. It is therefore possible that she gets dcvax-l.
Article:
Susan Bayh, former Indiana first lady, undergoes surgery for malignant brain cancer
Maureen Groppe and Kaitlin Lange IndyStar
Published 2:18 p.m. UTC May 23, 2018
https://eu.indystar.com/story/news/2018/05/22/susan-bayh-malignant-brain-tumor/633034002/
Longfellow95,
Remember what Michael Platten, MD, of Heidelberg University, said of the Liau et al study? He is of the same University as Wolfgang Wick.
Article: Addition of a Personalized Vaccine to Standard Therapy in Glioblastoma.
Quote:
“At this year's ASCO annual meeting, in an Education Session on vaccine therapy for glial tumors, Michael Platten, MD, of Heidelberg University, said of the Liau et al study: "This whole tumor vaccine was well tolerated, as this is the case with almost all vaccines. The primary endpoint, which was progression-free survival, has not been reported, but the median OS of the whole intention-to-treat population was 23 months and in the MGMT methylated patient population, was 34.7 months. We cannot, based on those data, determine efficacy of this approach.
Glioma patients may harbor spontaneous immune responses to tumor-associated antigens, and vaccine trials that employ these antigens are usually restricted to a class I presented epitopes, and are usually restricted to common HLA alleles, such as HLA A2, he continued. "Tumor-associated antigen vaccines are typically given as multi-peptide vaccines. We know peripheral immune responses may be associated with increased survival, but there is no firm evidence that this is a true, very good, reliable biomarker."
And quote:
"In conclusion, Platten said: "There's no evidence for clinical efficacy for vaccine therapies from randomized clinical trials. I think we should complement expression in leukemic stem cells and MHC prediction algorithms by ligandome analysis and intratumoral T-cell analyses to select appropriate antigens."
https://www.medpagetoday.com/reading-room/asco/immunotherapy/74315?xid=nl_mpt_DHE_2018-08-03&eun=g824783d0r&pos=1&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20-%20Salary%20Survey%202018-08-03&utm_term=Daily%20Headlines%20-%20Active%20User%20-%20180%20days
https://www.klinikum.uni-heidelberg.de/Michael-Platten.124948.0.html
https://www.klinikum.uni-heidelberg.de/Wolfgang-Wick.124949.0.html
For people who are interested, i found an EU study (more than 200 pg.):
Commercialisation of Advanced Therapies.
A Study of the EU Regulation on Advanced Therapy Medical Products
Faculty of Law University of Helsinki
Helsinki 2016
"The primary objective of this study is to analyse the benefits and limitations of the ATMP Regulation from the perspective of SMEs, academia and non-profit organisations that develop ATMPs. Secondly, it discusses the kind of amendment to the ATMP Regulation and related regulatory instruments and processes required to accelerate translation of research into advanced therapies and to facilitate commercialisation of ATMPs whilst ensuring the safety of patients. In addition, it analyses implications of the EU s limited mandate in the field of public health for developers of ATMPs. This study also investigates whether barriers to commercialisation relate to ATMPs as such or whether something else in the innovation system is impeding their market entry. As an example of potential ATMPs undergoing development, it also considers some specific, regulatory and moral patenting obstacles that impede the market entry of human embryonic stem cell-based products."
https://helda.helsinki.fi/bitstream/handle/10138/166228/Commerci.pdf?sequence=3&isAllowed=y
Agree, three patients had recurrent surgery. My point is that at least one patient does not come from the placebo group. So, even less crossover impact!
Sentiment,
Anyway, Advent Bioservices are hiring again!
July 19, 2018
Clinical Operations Coordinator
Advent Bioservices
-
London
Permanent
This job posting is no longer available on Indeed.
Related searches:
Clinical Operations Coordinator jobs in London
Advent Bioservices jobs in London
An exciting opportunity has arisen to join an emerging contract bioservices organisation providing GMP manufacturing services and process development for novel cell and gene therapy products. This is an exciting role for a high calibre Clinical Operations Coordinator. The Clinical Operations Coordinator will report to the Production Manager and will be based in London.
Job Description
The Clinical Operations Coordinator will be closely linked to the manufacturing team and should demonstrate a pro-active approach in which they can take responsibility for their own activities. Team play and strong communication skills are essential.
The Clinical Operations Coordinator is responsible for facilitating the relationship between Advent, the client, the clinic, blood collection centres, the patient and any vendors (such as couriers).
Cell and gene therapy products are very often patient specific and are made from patient or donor material; supply of material is time and temperature sensitive and there needs to be close coordination for collection and delivery of materials to be used in manufacture and for dispatch of products to the clinic for administration to a specific patient.
The post holder will work closely with GMP Production Scientists and Quality Assurance staff and facilitate the efficient delivery of cellular therapy products for clinical use. They will ensure that appropriate guidelines are available to third party sites and that appropriate documentation, such as virology screening and patient consent, is received to allow manufacture of products. The post holder will visit UK clinical sites if required and provide support and training to hospital clinical teams.
Responsibilities
The role includes but is not limited to:
• Manage relationship with patient or their family
• Manage relationship with physician
• Key point of contact with client
• Logistics including transport of starting material/tissue to the Advent manufacturing team at the Royal Free Hospital and final product to treatment site
• Responsible for ensuring that the necessary documentation is received by Advent
• Support clinical sites and aphaeresis centres with documentation and treatment administration
Job Types: Full-time, Permanent
Salary: £35,000.00 /year
Experience:
• scientific: 1 year
• clinical operations: 1 year
Education:
• Bachelor's
29 days ago - save job - report job
https://www.indeed.co.uk/viewjob?t=clinical+operations+coordinator&jk=0456de88bbd9b59a&_ga=2.145556146.706531030.1531736450-763207608.1525964574
Flipper44,
You write:
“There was likely little crossover impact, because only 3 patients in the entire trial received DCVax-l after recurrent surgery.”
At least one patient received DCVAX-L before recurrent surgery.
Love and Bright Light for Sunday Dennis
March 1, 2017
·
Lots has happened in the past few months. At the end of October, Sunday had another brain surgery to remove the mass and results came back as another tumour. The surgeon thought he was able to remove most or all of the tumour, however Sunday was left with loss of peripheral vision in her left eye and numbness on her left side, effecting her arm and leg. The hopes was that once the swelling went down everything would return to normal. Moving forward with treatment, her oncologist recommended a cocktail of drugs to include a drug that prevents tumour cells from making blood vessels, called Avastin, in combination with chemotherapy. Sunday also automatically moved into the open arm of the DCVax clinical trial where she would be guaranteed to receive her vaccine. When we arrived in Seattle to begin the open arm of the clinical trial, we were informed that the shot they had for her that day was her last available vaccine and that she had been receiving her vaccine all along. Being that the tumour grew back while she was receiving the vaccine means we did not get the results they were hoping for. Then in December, after a short six week recovery mode, we jumped right into treatment mode and Sunday started with this other aggressive treatment in hopes that Avastin would starve the cells and chemo would go in and wipe it all out. We went down this last week for her most recent MRI and unfortunately did not get the news we were hoping for. The MRI showed something is growing again which means the tumour is resistant to the chemotherapy. They have taken Sunday off chemo, it was ineffective and making her really sick, but will continue with Avastin as it seems to be effective in preventing new blood vessels from forming. Her oncologist recommended she go home and through diet and exercise get her immune system as strong as she possible can. As well, to try any alternative treatments we think would be beneficial. So here we are, researching, reaching out and looking for all possible treatments that could battle this tumour and be beneficial to her immune system. We have lots of irons in the fire and are hoping so badly we find a successful treatment soon. It’s been a challenging couple of years, but Sunday continues to persevere with so much dignity, and strength and beauty and wisdom and compassion and love. She is a constant inspiration!!! Now that she’s off chemo, Sunday’s starting to get some colour back in her cheeks, has more of an appetite, is able to be up and out of bed and we’ve been going for short walks. Please keep positive thoughts, high hopes, lots of strong prayers and live in LOVE!!!
https://www.facebook.com/Love-and-Bright-Light-for-Sunday-Dennis-510613112411830/
Flipper44,
Thank you for sharing the video!
POSTnotes
The Parliamentary Office of Science and Technology produces independent, balanced and accessible briefings on public policy issues related to science and technology.
Regulating Advanced Therapies
Published Friday, November 17, 2017
https://researchbriefings.parliament.uk/ResearchBriefing/Summary/POST-PN-0567#fullreport
"As complex therapies, ATMPs present a number of challenges to developers, regulators, and healthcare providers. They require a high level of expertise to develop and produce, which makes them expensive to market. Regulators have found it difficult to integrate their biological variability into pre-existing guidelines. Healthcare providers also face issues based on their complexity and expense. However, some national healthcare agencies have found creative solutions in funding them."
Full report:
Overview
? ATMPs are mainly regulated by EU law in which the UK’s regulatory bodies currently have a strong voice.
? The UK has a strong ATMP sector, concentrated primarily in academia and small biotechnology firms.
? ATMPs are expensive to develop and administer but several countries use flexible reimbursement mechanisms to fund their use in patients.
? ATMPs offer potential cures for diseases that currently lack them or are expensive to treat long-term.
? Retaining harmonised ATMP regulation with the EU after Brexit is seen as key for patient access, clinical research, and for the UK to retain its lead in the field.
http://researchbriefings.files.parliament.uk/documents/POST-PN-0567/POST-PN-0567.pdf
Germany, Dornstetten
Hallwang Private Oncology Clinic
April 26
Dear facebook friends and family,
we would like to share with you Jayden’s story. Jayden was diagnosed with glioblastoma multiforme just last year, one month before his 17th birthday. He had to undergo surgery and combined radiotherapy with temozolomide. Temozolomide was then discontinued, as the tumor reocurred, and another surgery was performed followed by chemotherapy. In the last months, Jayden´s condition worsened rapidly with increased immobility and loss of vision. He was unable to open his left eye. That is when Jayden first came to the Hallwang Clinic, and was started on a combined immunotherapeutic strategy. Now, 2 months later, Jayden’s condition has improved, he has started moving his legs and arms again, and is able to open his left eye occasionally. It is still a way to go, but we are happy Jayden is gaining more strength every day now.
https://www.facebook.com/414100488682843/photos/a.1003332896426263/1771376572955221/?type=3&theater
Stephen J Powell
Aug 15 23:13
This has to be the hardest post as a parent I’ve ever had to write, We were given the devastating news last week that Jayden had got an infection! The treatment was working but the tumour was to aggressive, we were told that Jayden would come home to be around his loved ones to be happy, Jayden my beautiful smiling son passed away peacefully in his sleep at 5.15 this morning. He was the toughest boy I know but we were just to late getting the treatment in time! We would appreciate it if you would respect our wish and leave us to grieve at this time. Thank you all for all the support you have given to Jayden, he really couldn’t believe how much he was truly Loved. From myself and family thank you
https://www.facebook.com/groups/FAMILYFOREVERJP/
EllaLouise? @EllaLouPow
The early hours of this morning my 17 year old cousin Jayden lost his battle to cancer! The Brightest star and sweetest angel will now join his Nan’s in paradise. Love you Jayden! #RestInPeace #SweetAngel
The early hours of this morning my 17 year old cousin Jayden lost his battle to cancer! 💔😭 The Brightest star and sweetest angel will now join his Nan’s in paradise. Love you Jayden! #RestInPeace #SweetAngel pic.twitter.com/AqkILynOyL
— EllaLouise (@EllaLouPow) August 16, 2018
Flipper44,
Appraisals that started development before April 2018 will use the pre-April 2018 process.
https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-technology-appraisal-guidance/process
We use 3 processes for assessing technologies: the single technology appraisal, the multiple technology appraisal and the fast track appraisal.
Single technology appraisal (STA)
This is a technology appraisal that assesses a single drug or treatment.
When it's used
We use the STA process for new technologies - usually new pharmaceutical products or license extensions for existing products. We also use it for reviews of some published appraisals.
This process enables us to produce guidance soon after the technology is introduced in the UK.
We updated our STA process in April 2018. Single technology appraisals developed from April 2018 onwards will use the updated process. Appraisals that started development before April 2018 will use the pre-April 2018 process.
Multiple technology appraisal (MTA)
This is a technology appraisal that assesses several drugs or treatments used for 1 condition.
When it's used
We use this if a new topic for an appraisal is particularly complex and not suited for the single technology appraisal process. It's also used for reviews of published appraisals.
Fast track appraisal (FTA)
On 1 April 2017 we introduced a fast-track appraisal for technologies that offer exceptional value for money.
The aim is to provide quicker access for patients to the most cost-effective new treatments.
When it's used
A technology will be appraised through the FTA process if:
• The company's base-case incremental cost-effectiveness ratio (ICER) is less than £10,000 per quality-adjusted life year (QALY) gained.
• It is likely that the most plausible ICER is less than £20,000 per QALY gained, and it is highly unlikely that it is greater than £30,000 per QALY gained.
or
• A cost comparison case can be made that shows it is likely to provide similar or greater health benefits at similar or lower cost than technologies already recommended in technology appraisal guidance for the same indication.
If a positive recommendation is made through the FTA process, NHS England/commissioners have committed to providing funding for the technologies within 30 days of guidance publication.
Marzan,
Your post:
No wonder John McCain is doing well. He must be on DcVaxL, imo.
Who knows, anyway his daughter Meghan McCain believes immunotherapy is the future!
Meghan McCain? account @MeghanMcCain
"This is incredible - immunotherapy truly is the future. So grateful for all the cancer scientists and researchers for their continued fight to find a cure."
This is incredible - immunotherapy truly is the future. So grateful for all the cancer scientists and researchers for their continued fight to find a cure. https://t.co/bvI983xmWV
— Meghan McCain (@MeghanMcCain) June 4, 2018
Sentiment,
I agree… the journal is a bit of a complex math problem to try and piece together.
In certain places the mOS chart is too overlapping to distinguish.
I analyzed the other 2 charts (MGMT methylated -unmethylated) looking for additional censored ticks.
I found 2 additional censored ticks in the section between 19 - 20 month and one additional in the section between 24 – 26 month.
Conclusion : I count 30 censored ticks between 18 and 23.1 month and 37 censored ticks between 23.1 and 36 month.
30 + 37 = 67.
After reviewing the ASCO 2018 video (Marnix Bosch), I found additional information about the interim analysis; 19m,22s. Look at the end of the chart.
https://www.nwbio.com/dcvax-personalized-dendritic-cell-vaccines/
If you watch this video you will find additional information about the trial on sec.40. It's a date.
https://twitter.com/ADOLPHUSST/status/1001549376316235777
Sentiment,
Thank you for the great work!
ASCO 2018 Presentation for DCVax-L - Sunday, June 3, 2018 - transcribed
Linda Powers
Quote:
“So, one last point before we start our line up is a correct-the-record point - there’ve been a lot of claims flying around since our publication came out. And one of the claims that some folks have put out, including a group in the UK, is that this treatment will never be viable because the cost will be impossible because it costs 250,000 pounds sterling per year. That is factually wrong. It is just wrong. That information was not checked with us. It has never been the case. It is not the case. So… suffice it to say we’ve worked for years to make DCVax a practical product with the goal that it will be widely available and viable.”
30 May 2018 by Katie Sheen.
BLOG
Our response to the results of the DCVax®-L immunotherapy trial.
https://www.braintumourresearch.org/media/our-blog/blog-item/our-blog/2018/05/30/our-response-to-the-results-of-the-dcvax--l-immunotherapy-trial
Quote:
“Our primary worry stems from the fact that this treatment is currently only being offered to people in the UK who can either raise sufficient funds or afford to pay the £250,000 needed to access the treatment privately. Families are selling their houses, cashing in their pensions and life insurances or increasing their debts in order to keep loved ones alive. What happens when the money runs out and they can’t afford any more injections? What about all the people who may now feel that their only hope lies with this treatment, but who simply can’t raise that much money?
This is not always the case with promising new treatments, which are usually only available to those participating in a trial that is free. The situation with the DCVax®-L vaccine has arisen because the trial that has been reported on was closed to further patients in 2016, which means that patients hearing about these promising results are not able to volunteer to participate.
We must question whether it is ethical to make the vaccine available privately, due to these issues around affordability and access: is it reasonable to at least give some people the option to pay for it, or not? Will health insurance companies foot the bill, given this new data?
In the longer term, could the NHS afford to pay for such an expensive treatment?
The hope is that as the technology develops costs will fall, but how long will this take? Where will the Centres be that can offer the technique? Even the first step requires tissue taken from surgery to be flash frozen - something that is not universally available in all NHS hospitals.
Whenever trials publish such early stage data, we must ensure that they are not giving false hope and putting families into a situation where they have to go into debt or seek help from their communities through fundraising in order to access these potentially promising treatments, particularly when the data is hopeful but not yet clear.
This situation highlights even more strongly than before the necessity for increasing the funding available for brain tumour research: Recent funding announcements from the government and CRUK are encouraging but is still not enough. We urgently need to get UK-based trials open for patients that are at the cutting edge of new approaches. They must be given the opportunity, regardless of their financial status, to choose to get involved in clinical trials. Only then will such announcements provide realistic hope for the future.
We are engaging with pharma, bio-tech and the UK Government to get our questions answered.”
Comment:
Kevin Quinn Mon Jun 04 2018:
Quote:” You stated:- "In the longer term, could the NHS afford to pay for such an expensive treatment? The hope is that as the technology develops costs will fall, but how long will this take? Where will the Centres be that can offer the technique? Even the first step requires tissue taken from surgery to be flash frozen - something that is not universally available in all NHS hospitals." Well, I would appreciate if you took the effort to find out some of the answers to your questions, because most of the answers are readily available. I can tell you now that other immunotherapies such as the approved Car-T therapies cost 2 to 3 times the cost of DCVax. The immune checkpoint inhibitors are more expensive in terms of likely total cost. They have an inferior toxicity profile and a much lower response rate. You really should know all of this, if you hope to be an informed resource for cancer patients. If you are aware of the role of NICE then you will know how they undertake technology assessments, and how they assess for survival benefit, quality of life, safety and value for money. They use a formula called Quality Adjusted Life Years.”
Comment:
Jeannine Walston Tue Jun 05 2018
Although not always the case for all GBM patients receiving DCVax-L, I have met some long-term GBM survivors treated with DCVax-L at University of California, Los Angeles. They include: Jennifer Sugioka, a 17 year GBM survivor; Brad Silver, a 14 year GBM survivor; Elijah Luyten, MD, a 10 year GBM survivor; Gallia Kistler, a 6 year GBM survivor; and, Jamil Newirth, a 6 year GBM survivor. (published in August 2017 by Jeannine Walston)
Sentiment,
mOS is at 23.1 month. That is event 166 (ITT 331/2)
11 LTFU between 0 an 23.1 months
166-11= 155 step downs (115 patients died between 0 and 23.1 month)
Note: i count exactly 155 step downs. (on my way)
10 step downs between 23.1 and 24 months. ( 10 patients died)
26 step downs between 24 and 30 months (26 died)
16 step downs between 30 and 36 months. (16 died)
3 steps downs beyond 36 months. (3 died= my guess)
I guess 2 LTFU between 23.1 and 30 months
Conclusion:
155+10+26+16+3= 210 died. (at the time of the analysis)
11 + 2 =13 LTFU (at the time of the analysis)
210(died) + 13(LTFU) = 223 events at the time of the analysis.
108 patients alive at the time of the analysis.
223(died) + 108(alive)= 331 ITT
Note:exactly 44 patients lived at least 36 months at the time of the analysis! (see scientific publication)
IMO
Sentiment,
I agree that the longer drop counts as 2 and sometimes as 3!
You indicated every step down with little red dots and i see 18 between 30 and 36 months.
The last one is at 36 months and a few days.That's the moment one of the 44 patients died.
The first red dot is not at 30 months but at the end of month 29.
Conclusion: speaking about that section between 30 and 36 months:
7 censored and i believe alive at the time of the analysis.
16 died.(67-44=23 and 16+7=23)
Your post 185633
I count 25 red dots on the section between 24 to 30 months.
That red dot at 30 months belongs to this section. So you have 25 + 1= 26 died.
We know from ASCO 2018 that 115 patients lived 24 months or more.
115- 67 (30 months)= 48 patients.
48 – 26(died) = 22 censored between 24 and 30 months and i believe alive at the time of the analysis.
let's find out how many patients had surgery before March 15, 2015.
(Marnix Bosch did not give us that number)
331-223 (at 30 months) = 108 patients between September 15, 2014 and August 15, 2015.(11 months) That is an average of 10/month.
223 + 60 = 283.
If i look at the Enrollment Timeline i see 87% enrolled June 15, 2015 (3 months after surgery)
https://www.nwbio.com/Boston-slides-31Aug2017-v0.5.pdf
87% of 331 = 288
take the average of 288 and 283 = 285
placebo= 95
treatment=190
So where are the 108 patients alive at the OS curve.(at the time of the analysis)
I guess that 3 died of the 44 patients who lived for at least 36 months. That’s 41 alive.(after the 36 month timeline)
Between 24 and 36 months: 22 + 7 = 29 alive.
Conclusion: 108 – 29 – 41 = 38 patients alive between 19 and 24 months.
38 patients of a group of 46. (331-285=46)
Placebo: 4 (99-95)
Treatment: 42 (46-4)
Sentiment,
We know how many patients have lived at least 24 months at the time of the analysis.(see presentation Marnix Bosch ASCO 2018)
We can count the step downs between month 24 and month 30 and calculate exactly how many patients are still alive between month 24 and month 30.(at the time of the analysis)
We know that between September 15, 2014 and (approximately) August 15, 2015 108 patients have had surgery.
The only conclusion I can make when I look at the figures from the last 108 enrolled patients is that these patients do better than the first 223 patients.
Not only the last 48 patients do significantly better but also the 60 patients who were treated between September 15, 2014 and March 15,2015.
That is remarkable!
Sentiment,
Sorry, but you make a mistake. I hope to be able to explain it with the two groups separately.
Take the group of 182 patients. These are the patients with a surgery date equal or more than 36 months. (on the date of the analysis)
You know whether each patient is dead or alive.
If the patient is alive, he is censored. Censored patients are annotated by a small vertical line on the OS curve.
The OS curve goes from 0 to 36 months. You will see no vertical lines from that group of 182 because all these patients had surgery before March 15, 2014 (3 years before date of the analysis March 2017).
44 of the first 182 patients living at least 36 months.
The scientific paper tells us that 30% from these 182 patients are living at least 30 months.
182 x 30%= 55 patients.
That means that 11 patients (55-44) died between 30 and 36 months and you will see 11 step downs on the OS curve between 30 and 36 months for that group.
Now take the second group of 41 patients (223-182). You may assume that these patients behave the same way.
That means that of these 41 patients 30% = 12 will live at least 30 months.
This group of patients had their surgery between March 15, 2014 and September 15, 2014.
Every patient who is still alive will be marked on the OS curve with a vertical line between 30 and 36 months.
If you look at the OS curve, you see 7 censors.
Conclusion: of the 12 patients who have lived for at least 30 months, 7 are still alive and 5 have died between 30 and 36 months.( 5 step downs on the curve)
Now add the 2 groups together: 182+ 41 = 223 patients.
You have 55 + 12 = 67.patients who have lived at least 30 months and more.
You have 11 + 5 = 16 patients who died between 30 and 36 months.
On the OS curve you see 16 step downs in that timeline.
You see 7 patients who are still alive between 30 and 36 months.( 7 vertical lines)
16 died + 7 still alive = 23 patients.
67-23 = 44 patients after the 36 months mark.
Conclusion: If the 7 patients of the second group (41) were all living at least 36 months then you would have 51 patients at 223 and that is 22.8%.(55/223)
That is less than the 24.2% for the first group of 182 patients (44/182 = 24.2%)
Longfellow95,
Thank you for bringing the subject to our attention!
“Bernard-Arnoux 2016 is a cost effectiveness study comparing standard chemotherapy and radiotherapy with the addition of tumour treating field therapy compared to standard chemotherapy and radiotherapy alone in patients with grade IV astrocytoma. The study took a French health insurance perspective and reported outcomes in terms of cost per life year gained. Effectiveness data were taken from EF-14 trial (Stupp 2015) discussed in detail in the accompanying clinical evidence review.”
https://www.nice.org.uk/guidance/ng99/evidence/a-investigation-management-and-followup-of-glioma-pdf-4903134734
The cost-effectiveness of tumor-treating fields therapy in patients with newly diagnosed glioblastoma.
F. Bernard-Arnoux.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933490/
Comment in:
• Living in a material world: tumor-treating fields at the top of the charts. [Neuro Oncol. 2016]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933493/
Living in a material world: tumor-treating fields at the top of the charts.
Quote:
“In this issue of Neuro-Oncology, Bernard-Amoux and colleagues report on the results of a cost-effectiveness analysis evaluating the incremental benefit of TTFields for glioblastoma in the context of the French health care system. Their principal finding is that the use of TTFields in conjunction with standard of care chemoradiation is not within the realm of what is considered “cost-effective” by most regulatory bodies that have established explicit thresholds. While France does not use explicit thresholds, Commonwealth countries with national health systems, such as the UK, Australia, New Zealand, and Canada, generally consider treatment interventions that have ratios of $50 000–$100 000 per life-year gained to be cost-effective.5 In the US, regulatory authorities are prohibited from considering cost in making decisions about coverage, but informally, similar thresholds are used to label treatments as cost-effective.6
Cost-effectiveness analyses such as Bernard-Amoux et al's are determined on the basis of comparing 2 alternative strategies. In this case, the comparison is between chemoradiation plus TTFields versus standard chemoradiation. The incremental cost-effectiveness ratio (ICER) computes the cost of chemoradiation/TTFields versus that of chemoradiation while also assessing the benefits (expressed in terms of survival time) for these treatments. The ICER is the ratio of these differences.”
Quote:
“The ICER per life-year gained with TTFields in the Bernard-Amoux study, at €550 000, exceeds these figures by a factor of 5–10. As such, the onus is on the device manufacturer either to provide data justifying the price of TTFields or to bring the cost in line with other approved therapies providing comparable clinical benefit.”
Heidelberg University is a site for DCVax-L. However, this site was added after the halt.
You can check this by looking at the history on the clinicaltrials.gov site and looking at the trial sites. Heidelberg is added August 28, 2015. There is no contact person put there either.
Contact person : Dr. med. Christine Jungk
Oberärztin
Spezialisiert auf Hirntumorchirurgie und Neuroonkologie, Hydrocephalus
https://www.klinikum.uni-heidelberg.de/Klinische-Studien.120083.0.html
NOTE:
Sentiment,I found this after browsing the web:
"The reader comment section always adds a dimension to the comprehensive review of the recent progress, or lack thereof, in immunotherapy for GBM."
National Cancer Institute? account @theNCI
Can #immunotherapy succeed in glioblastoma? A research update on efforts to use the immune system to treat brain cancer: https://www.cancer.gov/news-events/cancer-currents-blog/2018/immunotherapy-glioblastoma … #ASCO18
https://twitter.com/NeuronOmega/status/1003285282496577536
Meirluc,
That’s correct. 166 OS evented (50% of the trial n=331).
ITT median isn’t a point of significance.
And the overall ITT might get worse, and there is a chance it will as not all 108 patients at the time of the analysis were 23.1 months out from surgery.
Post 184928
Your quote:
Finally, for the 100 patients the definition of long lived was never defined. It could have spanned the time lines of who knows, 24 to 70 months with a derived mOS of 40.5 months
We know 115 patients reached 24 months and 67 patients reached 30 months at the time of the analysis (March 2017) https://www.nwbio.com/dcvax-personalized-dendritic-cell-vaccines/.
You see 21 censors (maybe 22 or 20) on the graph between 24 and 30 months. I believe these censors are all patients still alive at the time of the analysis.That means that the definition of long lived patients = 100 patients reached 27 months from surgery at the time of the analysis( March 2017) (and look at the down steps)!
Your quote( post 184830):
of the 100, 65.9% had methylated MGMT? have they averaged out the degree of methylation over the entire cohort of 100 long live patients? I thought they would have a cut of point for degree of methylation that would characterize a patient as either met+ or met-.
Of 38 patients we are missing data.
Just imagine from 100 patients:
12 patients unknown.
58 patients methylated.
30 patients unmethylated.
So we have 58 X 100/88= 65,9% methylated MGMT.
And 30 X 100/88= 34,1% unmethylated MGMT.
Meirluc, of all the data we received you can calculate at what time a patient died after 23.1 month. (at the time of the analysis March 2017) Just do the calculation!
IMO
Longfellow95,
You say:Otherwise, just go with Optune...
Not in the UK for glioblastoma.
July 10, 2018
NICE:new guidance on the treatment of brain tumours.
1.2.26 Do not offer tumour-treating fields (TTF) as part of management of a newly diagnosed grade IV glioma (glioblastoma).
1.2.34 Do not offer tumour treating fields (TTF) as part of management of recurrent high-grade glioma.
https://www.nice.org.uk/guidance/ng99/chapter/Recommendations
New funding in brain tumour research.
David Jenkinson talks to ecancer at the Cancer Research UK Brain Tumour Conference 2018 in London about the collaboration between The Brain Tumour Charity and Cancer Research UK in order to fund new research in the brain cancer field.
Article:
The possibility of cancer immune editing in gliomas. A critical review
Víctor A. Arrieta, Bernardo Cacho-Díaz, Junfei Zhao, Raul Rabadan, Li Chen & Adam M. Sonabend
Article: e1445458 | Received 22 Jan 2018, Accepted 20 Feb 2018, Accepted author version posted online: 01 Mar 2018, Published online: 09 Apr 2018
https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1445458#.Wsuh_NX_3uo.twitter?platform=hootsuite
Quote: “Because of this mechanism of immune editing and the intrinsic molecular heterogeneity of gliomas, different strategies for immunotherapy should be used in order to target multiple antigens to mitigate antigen escape and avoid tumor recurrence.”
"Immunoediting"
From Wikipedia
https://en.wikipedia.org/wiki/Immunoediting
Yes and it's curious if you know this:
Craig Horbinski, MD, PhD – Lurie Cancer Center / Northwestern Medicine
And…….
Roger Stupp
A leading authority on the treatment of primary and metastatic brain cancer, Stupp will join Northwestern Medicine in April 2017 as a professor of Neurological Surgery. He will work collaboratively with other neuro-oncologists in the Division of Neuro-Oncology in the Department of Neurology and the Lurie Cancer Center’s Northwestern Brain Tumor Institute to help advance efforts to treat complex brain tumors medically.
http://cancer.northwestern.edu/news/2016/Stupp.html
Electric Scalp Device Prolongs Survival in Deadly Brain Cancer.
http://news.feinberg.northwestern.edu/2017/12/electric-scalp-device-prolongs-survival-in-deadly-brain-cancer/
Craig Horbinski
@CraigHorbinski
I am a molecular #neuropathologist at #Northwestern University who specializes in #braintumor research. My R01-funded laboratory studies IDH1 mutant #gliomas.
"First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma"
Craig Horbinski? @CraigHorbinski may 30
"Wow, check this out. Still preliminary, but the durations of survival are pretty doggone impressive! #glioma #BrainTumour #Glioblastoma #vaccine"
Craig Horbinski? @CraigHorbinski may 30
"especially for those patients whose tumors had MGMT promoter methylation, the addition of the vaccine seems to have extended their median survival to nearly three full years"
https://twitter.com/CraigHorbinski
Craig Horbinski
@CraigHorbinski
may 5
"Easy Reading Is Damn Hard Writing"
Nathaniel Hawthorne, 1804-1864
(legendary American novelist, but the same applies to scientific writing)
#quotesoftheday