NorthWest Biotherapeutics Inc (NWBO)

[Lykiri]

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.