Data collection agreement

This agreement relates to treating cystic fibrosis patients with:

Ivacaftor, tezacaftor and elexacaftor (Kaftrio®) in combination with ivacaftor for patients homozygous for the F508del mutation or heterozygous for F508del with a minimal function (MF) mutation.
Tezacaftor and ivacaftor (Symkevi®) in combination with ivacaftor for patients homozygous for the F508del mutation or who are heterozygous F508del mutation with a residual function mutation or specified rarer mutations.
Lumacaftor and ivacaftor (Orkambi®) for patients homozygous for the F508del mutation.
Ivacaftor (Kalydeco®) for patients with specified gating or rarer mutations or R117H mutation.

Parties to this agreement

NHS England and NHS Improvement, whose legal name is the NHS Commissioning Board and whose principal office is at Quarry House, Quarry Hill, Leeds, LS2 7UE ('NHSE&I').
The National Institute for Health and Care Excellence, a non-departmental public body established under primary legislation and based at 3rd floor, 3 Piccadilly Place, Manchester, M1 3BN ('NICE').
UK Cystic Fibrosis Trust, a charity dedicated to the interests of people living with cystic fibrosis, whose office is at 1 Aldgate, London EC3N 1RE ('Cystic Fibrosis Trust'), and the manager of the UK Cystic Fibrosis Registry.
Vertex Pharmaceuticals (Europe) Limited, a company incorporated in England having its principal place of business at Level 9, Paddington Central, 2 Kingdom Street, London W2 6BD, United Kingdom ('Vertex'), and licensed seller of lumacaftor/ivacaftor (Orkambi), tezacaftor/ivacaftor (Symkevi), ivacaftor (Kalydeco) and ivacaftor/tezacaftor/elexacaftor (Kaftrio) respectively.

Each a 'Party' and together the 'Parties'.

Agreement

In consideration of the promises, rights and obligations contained in:

this Agreement; and
the access agreement put in place between NHSE&I and Vertex in respect of the above-mentioned drugs,

the sufficiency of which is acknowledged by each of the Parties, it is agreed as follows:

1. Purpose of this agreement

1.1 NHSE&I and Vertex have concluded an access agreement to enable eligible patients in England access to treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor via the NHS.

1.2 The purpose of this Agreement is to describe the arrangements intended to capture the data that may address the clinical uncertainties in the evidence base concerning lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor to inform a future health technology appraisal by NICE. The clinical uncertainties in 3.1 have been identified by NICE's technology appraisal committee and in consultation with cystic fibrosis clinical experts and NICE's external assessment centre.

1.3 The NICE health technology appraisal(s) of lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor will use the process and methods in place at the time of the invitation to participate which will include taking account of all relevant considerations arising out of the interim access agreement, for these products as part of these appraisals.

1.4 The NICE health technology appraisal(s) will include indications (for lumacaftor/ivacaftor, tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor) that have received a marketing authorization from the European Medicines Agency applicable to the United Kingdom or the Medicines and Healthcare products Regulatory Agency at the time of scoping by NICE.

2. Commencement and period of agreement

2.1 This Agreement fully incorporates and expands the terms of a previous agreement (dated 11 November 2019) concerning access to treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and introduces further requirements concerning ivacaftor/tezacaftor/elexacaftor.

2.2 This Agreement and the new terms herein will commence on the date of publication of this Agreement on the NICE website, following execution of this Agreement by all parties and supersedes and replaces the previous agreement (dated 11 November 2019).

2.3 This Agreement will expire upon the earlier of either 2.3.1 or 2.3.2:

2.3.1 publication of NICE's recommendation following a health technology appraisal of the new evidence collected during the initial term of the interim access agreement; or

2.3.2 termination of the commercial access agreement between NHSE&I and Vertex which enables eligible patients in England access to treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor via the NHS.

3. Areas of clinical uncertainty with respect to lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor

3.1 The following key clinical uncertainties to be addressed by this Agreement have been identified from the original appraisal of lumacaftor/ivacaftor (NICE TA398) and recommendations made by the NICE commissioned independent external assessment centre. The parties agree that the uncertainties listed are applicable to lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor:

long-term (more than 1 year) treatment effects on absolute ppFEV1
the impact of treatment on lung function decline*†
discontinuation rates of Vertex therapies and reasons for discontinuation*
compliance rates of Vertex therapies*
comparative outcomes for different disease severities
comparative treatment pathway costs*
patient* † and caregiver quality of life impact, including patient age related differences
the rate of pulmonary exacerbations*†.

* denotes data items that were used in the economic model for TA398.

† denotes that in the context of the TA398 appraisal, these uncertainties related to the relative effect compared with other treatments or standard of care.

4. Sources of data

4.1 Data will be collected from patients who start or receive treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor during the term of this Agreement and patients who initiated treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor prior to this Agreement as part of Vertex's compassionate access scheme (called a 'Managed Access Programme', or MAP). Patients who stop treatment during this term will also continue to be monitored for disease deterioration and supported with other clinical measures.

4.2 Sources of data that could mitigate the key clinical uncertainties include:

Table 1: Primary and secondary sources of data collection

Source	Description
Primary source	Real world data collected by the UK Cystic Fibrosis Registry (detailed in table 2).
Secondary sources	Pharmacy home delivery data to inform compliance rates (compiled by Vertex). Vertex Quality of Life (QoL) study in the UK collecting patient and caregiver QoL. Ongoing Vertex clinical trials: VX 18 445-104 VX 17 445-105 VX18 445-109. Any other Vertex studies that will require data collection and are yet to be defined.

Description of data sources

4.2.1 UK Cystic Fibrosis Registry

The UK Cystic Fibrosis Registry includes data from consenting patients from all cystic fibrosis care centres and clinics in the UK, covering 99% of the UK cystic fibrosis population. The Registry holds information on demographics, treatment and health outcomes.

4.2.2 Pharmacy home delivery data

Vertex has existing arrangements in place with its contracted homecare delivery vendors for such vendors to periodically provide delivery volume and frequency data from which Vertex will estimate patient compliance and provide a summary report annually to the Interim Access Oversight Committee.

4.2.3 Vertex Quality of Life study in the UK

Vertex will conduct a study in the UK to capture data on Quality of Life (QoL) in patients and caregivers. The Cystic Fibrosis Questionnaire - Revised (CFQ-R) will be used to capture QoL data in patients. Generic instruments for QoL will be used as appropriate to capture data in caregivers. Results will be available prior to health technology assessment submissions to NICE and will be shared as academic in confidence with NICE. Vertex will provide:

the protocol for the QoL study no later than 3 months following commencement of the QoL study
high level updates on study status and interim outcomes as available at quarterly Interim Access Oversight Committee meetings.

4.2.4 Clinical trials

VX 18 445-104: patients 12 years and older with the following genotypes - F508del/gating or F508del/residual function. Outcomes - change in FEV1, quality of life. VX 18 445-104 expected target reporting of the Clinical Study Report (CSR) in [redacted]*.
VX 17 445-105: patients 12 years and older with the following genotypes - F508del/F508del or F508del/minimal function. Long-term extension (96 weeks) study including patients from the phase 3 trials - VX17 445-102 and VX17 445-103. Outcomes - change in FEV1, quality of life. VX 17 445-105 expected target reporting of the CSR in [redacted]*.
VX18 445-109: patients 12 years and older with the F508del/F508del genotype. 24 week trial. Outcomes - quality of life, change in FEV1. VX 18 445-109 expected target reporting of the CSR in [redacted]*.

*Timelines for reporting are subject to change.

4.3 The data from the Secondary Sources detailed in table 1 is owned and managed by Vertex but shared with the Interim Access Oversight Committee set out in clause 11.1 for the purpose of oversight and awareness by the Interim Access Oversight Committee and to facilitate the provision of discretionary advice on the data collection processes. Data from Secondary Sources shared by Vertex as part of this Agreement will be subject to the confidentiality, retention, intellectual property and data protection policies of Vertex and the Secondary Sources are not subject to direct control, by NICE, NHSE&I or the Interim Access Oversight Committee.

4.4 Furthermore, Vertex retains all commercial and legal rights and discretions on the management of its activities which have been included in the Secondary Sources including the setting of protocols, study governance, data collection and sharing and intellectual property rights. In agreeing to provide data derived from the Secondary Sources, Vertex does not relinquish its rights to or decision-making power over the Secondary Sources which form part of Vertex normal business operations outside of this Agreement. For example, in agreeing to provide information relating to a clinical trial, Vertex is not, within this Agreement, committing to run or manage such trial in any particular manner and NICE and NHSE&I shall have no authority to determine the parameters of the Vertex clinical trial, study or any other data generating programme or in Vertex management of its external vendors.

Table 2: Outline of data to be collected from the UK Cystic Fibrosis Registry

The Parties agree that the recommended frequency and upload of the listed assessments is beyond the standard of care and routine upload frequency in current practice, however where possible assessments are encouraged to be conducted and uploaded using the UK Cystic Fibrosis Registry 'encounter' form, as per the recommended frequency in table 2.
At a minimum, assessments should be conducted and uploaded annually, using the UK Cystic Fibrosis Registry 'annual' form, by the 31 January deadline.
Further agreements will be established by Vertex with the Cystic Fibrosis Trust as per 8.1 and 8.2, which may redefine the data collection requirements in table 2.

Key data items

It is expected that the following data items will be collected as part of routine clinical practice; upon feasibility of these data being captured by clinicians in the UK Cystic Fibrosis Registry, where available these data will be part of the dataset.

Ideally, data should be captured in the UK Cystic Fibrosis Registry as per the below recommended frequency. At a minimum, assessments should be conducted and uploaded annually using the UK Cystic Fibrosis Registry 'annual' form.

Assessment	Rationale	Recommended frequency: Baseline/Pre-treatment	Recommended frequency: 3 monthly	Recommended frequency: 6 monthly	Recommended frequency: Annually	Data collection tool
Genotype (rarer mutation patients only)	Baseline characteristics	Yes	No	No	No	-
Poly-T status (R117H patients only. Patients are not required to have genetic retesting if genotyping has already been performed)	Baseline characteristics	Yes	No	No	No	UK Cystic Fibrosis Registry
CFTR modulator start dates	Baseline characteristics	Yes	No	No	No	UK Cystic Fibrosis Registry
ppFEV1 - cystic fibrosis clinic/hospital spirometry	Assessment of lung function	Yes	Yes	No	No	UK Cystic Fibrosis Registry
ppFEV1 - home spirometry	Assessment of lung function	Yes	Yes	No	No	UK Cystic Fibrosis Registry
BMI (for patients aged 18 or over)	Assessment of non-respiratory symptoms	Yes	Yes	No	No	UK Cystic Fibrosis Registry
Height and weight (for patients aged over 18)	Assessment of non-respiratory symptoms	Yes	Yes	No	No	UK Cystic Fibrosis Registry
Lung transplant events	Assessment of survival	No	No	Yes	No	UK Cystic Fibrosis Registry
Use of intravenous antibiotics - hospital and home	Proxy for assessment of pulmonary exacerbation	No	No	Yes	No	UK Cystic Fibrosis Registry
Microbiology	Assessment of treatment efficacy	No	No	Yes	No	UK Cystic Fibrosis Registry
IV and non-IV hospital admissions	Proxy for assessment of hospital admissions	No	No	Yes	No	UK Cystic Fibrosis Registry
Cystic fibrosis related diabetes status	Assessment of non-respiratory symptoms	No	No	Yes	No	UK Cystic Fibrosis Registry
Treatment discontinuation status, including date of discontinuation, and reasons for treatment discontinuation - all treatment (not just CFTR modulators)	Assessment of treatment discontinuation rates	No	No	Yes	No	UK Cystic Fibrosis Registry
Mortality	Assessment of overall survival	No	No	Yes	No	UK Cystic Fibrosis Registry
Faecal elastase	Assessment of pancreatic insufficiency	No	No	No	Yes	UK Cystic Fibrosis Registry
Quality of life (CFQR) - upload of domain scores or total score	Assessment of patient quality of life	6-monthly	6-monthly	6-monthly	6-monthly	UK Cystic Fibrosis Registry

Additional data collections

Where possible and where the infrastructure of the UK Cystic Fibrosis Registry allows, the following data items are considered to be highly relevant to any future evidence submissions and should be uploaded to the Registry if collected.

Assessment	Rationale	Recommended frequency	Data collection tool
Sweat chloride	Assessment of sweat chloride	Annually	UK Cystic Fibrosis Registry

5. Data collection responsibilities

5.1 NHSE shall seek to ensure, to the extent reasonably possible, that the treating clinician collects the assessment outcomes and uploads these to the UK Cystic Fibrosis Registry, for patients who have consented to provide data to the Registry as per table 1 (at a minimum annually using the annual review form, by 31 January each year).

5.2 The Cystic Fibrosis Trust, via the UK Cystic Fibrosis Registry, will be responsible for providing the following outputs to NICE, NHSE&I, and Vertex during the Agreement term as outlined in table 3 (further detail on report content will be outlined in the data protocol as per 8.2).

5.3 The parties agree to perform a review of the reporting schedule detailed in table 3 in February 2022 to consider any amendments to the reporting schedule in view of the findings from reports 1, 2 and 3, and encounter data entry rates.

5.4 Vertex will be responsible for providing an evidence submission to NICE for the purpose of a health technology appraisal(s) of lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor as per the timelines confirmed by the NICE planning and operations team.

5.5 Vertex will be responsible for providing NHSE&I with monthly uptake data per centre on ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor during the term of this Agreement.

5.6 In respect of the collated data derived from 4.2.2, 4.2.3 and 4.2.4, Vertex shall not be obligated to supply any commercially sensitive information or release any information the provision of which may impact on any intellectual property rights of Vertex or which is information not already lawfully subsisting in the public domain.

Table 3: Cystic Fibrosis Trust reporting schedule

Report number	Title	Delivery date	Purpose
1	Interim summary report	September 2020	To review the impact of the COVID-19 pandemic on the analysis plan and inform amendments to the data protocol. This report will be used to determine whether real-world data collection is proceeding as anticipated and will not form part of the NICE guidance review.
2	Interim analysis of outcomes	July 2021	Data monitoring review by the Interim Access Oversight Committee.
3	Interim summary report	February 2022	Data monitoring review by the Interim Access Oversight Committee. This report will be used to determine whether real-world data collection is proceeding as anticipated and inform a review of the reporting schedule as per 5.3. This report will not form part of the NICE guidance review.
4	Interim summary report, based on interim data cut approximately 1 May 2022	May 2022	Data monitoring review by the Interim Access Oversight Committee. This report will be used to determine whether real-world data collection is proceeding as anticipated and will not form part of the NICE guidance review.
5	Interim analysis of outcomes, based on an interim data cut from the UK Cystic Fibrosis Registry	October 2022	To support the first Vertex evidence submission to NICE for the purpose of the guidance review detailed in 1.2.
6	Final analysis of outcomes	June 2023	To support the final Vertex evidence submission to NICE for the purpose of the guidance review detailed in 1.2.

6. Patient eligibility

6.1 In order for patients to be considered as eligible to participate in this data collection exercise, such patients shall be:

located in the United Kingdom; and
eligible to receive treatment using either ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor during the term of this Agreement; and
within the licensed indications for ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor in place at the date of execution of this Agreement;

ivacaftor licensed indication:

Patients must be aged 6 months or older; and
have a confirmed mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) of at least one copy of the G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N and S549R (also known as gating mutations); or
Patient is aged 6 months or older with at least one copy of the R117H mutation in the CFTR gene.

lumacaftor/ivacaftor licensed indication:

All patients aged 2 years or older and confirmed homozygous F508del mutation of the CTFR gene

tezacaftor/ivacaftor licensed indication:

All patients aged 12 years or older and confirmed homozygous F508del mutation of the CTFR gene or confirmed heterozygous F508del mutation of the CTFR gene AND have one of the following CTFR gene mutations: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272 26A→G, and 3849+10kbC→T.

ivacaftor/tezacaftor/elexacaftor license indication:

i. All patients aged 12 years and older who are homozygous for the F508del mutation in the CFTR gene or heterozygous for F508del in the CFTR gene with a minimal function (MF) mutation corresponding to either no production of a CFTR protein or a CFTR protein that is not responsive to ivacaftor and tezacaftor / ivacaftor in vitro.

within the indications for ivacaftor or tezacaftor/ivacaftor outlined in the NHSE&I Clinical Commissioning Urgent Policy Statement Ivacaftor and tezacaftor/ivacaftor for cystic fibrosis: 'off-label' use in patients with named rarer mutations [200809P]. These rarer indications are not currently included within the EMA license for ivacaftor or tezacaftor/ivacaftor and may be outside of the scope of the future NICE health technology appraisal of tezacaftor/ivacaftor.

Ivacaftor rarer mutation indications

people aged 6 months and over who are heterozygous for the CFTR mutations listed under the eligibility criteria for ivacaftor as a monotherapy in table 4.

Tezacaftor/ivacaftor rarer mutation indications

people aged 12 years and older who have at least one copy of any of the named mutations (listed in table 5) in the CFTR gene responsive to tezacaftor/Ivacaftor.

receiving treatment with either ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor during the period in which the data is collected pursuant to this Agreement.

Table 4: Ivacaftor as a monotherapy, rarer mutation indications

Therapy	Named mutations	Mutations with ‘varying clinical consequence' (VCC)
Ivacaftor as a monotherapy for patients aged 6 months and over	A1067T A455E D110H E193K E56K E831X K1060T L206W P67L R117C R347H R352Q S945L 2789+5G>A 3272-26A>G 3849+10kbC>T 711+3A->G	D110E* D1152H* D1270N* D579G* F1052V* F1074L* R1070W* R74W* S977F*

Table 5: Tezacaftor/Ivacaftor as a combination therapy, rarer mutation indications

Therapy	Named mutations	Mutations with ‘varying clinical consequence' (VCC)
Tezacaftor/Ivacaftor as a combination therapy for patients aged 12 years and over	A1067T A455E D110H E193K E56K E831X K1060T L206W P67L R117C R347H R352Q S945L 2789+5G>A 3272-26A>G 3849+10kbC>T 711+3A->G	D110E* D1152H* D1270N* D579G* F1052V* F1074L* R1070W* R74W* S977F*

6.2 All patients located in the United Kingdom who received treatment pursuant to Vertex's compassionate access scheme (MAP) - which provided free ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor for the patients most in need, prior to the access agreement being executed and implemented - will transfer to product supplied to them on the terms contained in the access agreement.

6.3 If the patient's genotype is unknown, an accurate and validated genotyping method should be performed before starting treatment to confirm the presence of an indicated mutation in the CFTR gene. Cystic fibrosis clinical teams will need to review existing patients prior to changing or initiating new medications.

6.4 Future therapeutic indications (for ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor or ivacaftor/tezacaftor/elexacaftor) that receive a marketing authrorization from the European Medicines Agency applicable to the United Kingdom or the Medicines and Healthcare products Regulatory Agency during the term of the interim access agreement will automatically be considered part of this Agreement and formalised through an addendum to the interim access agreement executed between the signatory parties.

6.5 NHSE&I shall seek to ensure, to the extent reasonably possible, that treating clinicians encourage patients to attend either a clinic or virtual appointment every 6 months after treatment initiation.

6.6 NHSE&I shall seek to ensure, to the extent reasonably possible, that treating clinicians follow the recommendations and precautions set out in the Summary of Product Characteristics for each drug/treatment.

6.7 The parties agree that patients who are eligible for NHS treatment in England but have been sourcing these products abroad or through private prescriptions in England can access treatment via the interim access agreement so long as they are eligible as per lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor full licensed indications, or NHSE&I's Clinical Commissioning Urgent Policy Statement for Ivacaftor and Tezacaftor/Ivacaftor for Cystic Fibrosis: 'off-label' use in patients with named rarer mutations [200809P] (in the case of rarer mutation patients), and their treating centre confirms that they are eligible for NHS treatment in England. In all these cases, the parties agree that it is for the patient or family to ensure that there is an appropriate handover between the organisation currently treating the patient and the NHS treating centre in England.

6.8 Ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor must only be prescribed by physicians with experience in the treatment of cystic fibrosis, working within NHS England commissioned cystic fibrosis services in line with the respective market authorisations or NHSE&I's Clinical Commissioning Urgent Policy Statement for Ivacaftor and Tezacaftor/Ivacaftor for Cystic Fibrosis: 'off-label' use in patients with named rarer mutations [200809P] (in the case of rarer mutation patients).

Clinicians should be familiar with the marketing authorisation(s) of lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor and NHSE&I's Clinical Commissioning Urgent Policy Statement for Ivacaftor and Tezacaftor/Ivacaftor for Cystic Fibrosis: 'off-label' use in patients with named rarer mutations [200809P] (in the case of rarer mutation patients), and where applicable cease treatment where patients are unable to benefit from the treatment.

7. Data protection

7.1 Patient data collected as part of this Agreement will be in accordance with all applicable data protection legislation, including but not limited to the European Union's General Data Protection Regulation and any equivalent legislation applicable in the UK.

7.2 All patient data will be treated in accordance with the UK Cystic Fibrosis Registry privacy policy. Any further data collections established during the term of this Agreement that will contribute to the NICE health technology appraisal of lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor are required to have a schedule for data processing in place outlining the data controller(s) and processor(s).

8. Data analysis plan

8.1 The Parties shall work together to ensure that relevant aggregated data required for the NICE reconsideration of guidance for lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor is available as per the schedules detailed in section 4 and table 3. Specifically, Vertex shall be responsible for ensuring that an appropriate revised agreement is in place with the Cystic Fibrosis Trust within 2 months following the commencement of this Agreement, to ensure that necessary data contained in the UK Cystic Fibrosis Registry is analysed for this purpose.

8.2 Vertex, in consultation with the Cystic Fibrosis Trust, shall amend the current data protocol within 6 months following the commencement of this Agreement, for review by NICE and NHSE&I, and presentation at the next Interim Access Oversight Committee meeting following this milestone. Further amendments to the data protocol may be required subject to recommendations from the Interim Access Oversight Committee, and Primary and Secondary Sources.

9. Ownership of the data

9.1 The data collated from the Primary Source will be owned by patients and managed by the Cystic Fibrosis Trust but shared in aggregate, anonymised form with NHSE&I, NICE (including the external assessment centre), Vertex, and the Interim Access Oversight Committee for the purpose of assessing the benefit of lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor.

9.2 Data collected into the UK Cystic Fibrosis Registry and included in any output reports as part of this Agreement will be subject to the retention and publication policies of the Registry.

9.3 Data about and collated from the Secondary Sources will be owned by Vertex but shared in aggregate (and/or anonymised) form with NHSE&I, NICE (including the external assessment centre), and the Interim Access Oversight Committee for the purpose of assessing the benefit of lumacaftor/ivacaftor, tezacaftor/ivacaftor and ivacaftor/tezacaftor/elexacaftor.

9.4 Data about and collated from the Secondary Sources and included in any output reports as part of this Agreement will be subject to the retention and publication policies of Vertex.

10. Funding for data collection and analysis

10.1 Vertex will be expected to pay direct and associated costs as agreed between the Cystic Fibrosis Trust and Vertex for:

database management - including quality assurance
data analysis
costs associated with accessing data, registry database amendments and linking data to other sources (if applicable)
any other costs identified that are relevant to data collection and analysis associated with the uncertainties outlined in 3.1.

10.2 Vertex shall provide NICE and NHSE&I assurances that the existing agreements concerning the resources required to operationalise data collection and analyses will be updated to include ivacaftor/tezacaftor/elexacaftor (Kaftrio) with relevant third parties within 2 months of the publication of this Agreement.

10.3 The relevant terms of the agreements specified in 10.2 should be presented to the Interim Access Oversight Committee for review at its first meeting (i.e. no later than 2 months after the commencement of this Agreement).

11. Monitoring arrangements

11.1 NICE will convene an Interim Access Oversight Committee with representation from all Parties, expert treatment centres located in England and a NICE external assessment centre.

11.2 The Interim Access Oversight Committee exists to oversee the operation of all aspects of this Agreement and to address issues that may arise throughout the term of this Agreement. A detailed description of the Interim Access Oversight Committee function will be available in a Terms of Reference document produced by NICE.

11.3 The Interim Access Oversight Committee will meet at a minimum of 6-monthly intervals throughout the interim access agreement period.

11.4 The NICE external assessment centre for the purpose of this Agreement is the Medical Physics and Clinical Engineering group at Newcastle upon Tyne Hospitals NHS Foundation Trust. An executed contract is in place between NICE and the external assessment centre which includes confidentiality terms no less strict than the confidentiality terms upon which NICE received the information.

12. Governing law

12.1 This Agreement shall be governed by the laws of England and Wales, and subject to the exclusive jurisdiction of its courts.

13. Miscellaneous

13.1 This Agreement creates rights only for the Parties. It may not be enforced by any third party.

13.2 This Agreement may be executed in any number of counterparts, each of which when executed and delivered shall constitute a duplicate original, but all the counterparts together shall constitute one agreement. Transmission of the executed signature page of a counterpart of this Agreement by (a) fax or (b) email (in PDF, JPEG or other agreed format) shall take effect as delivery of an executed counterpart of this Agreement. If either method of delivery is adopted, without prejudice to the validity of the agreement thus made, each Party shall provide the other with the original of such counterpart as soon as reasonably possible thereafter. No counterpart shall be effective until each Party has executed and delivered at least one counterpart.