Access resources and support related to the delivery of complex innovative design cancer trials in the UK.
Delivery of Complex Innovative Design Cancer trials
We’ve worked with key stakeholders to address some of the challenges associated with the set-up and conducting research in a system as complex as the NHS.
Traditional cancer drug development is increasingly being replaced by trials that answer multiple clinical questions. These are collectively termed Complex Innovative Design (CID) trials.
CID trials assess the safety and toxicity of novel anticancer medicines. They also test their efficacy in biomarker-selected patients, specific cancer cohorts, in combination with other agents. They can be adapted to include new cohorts and test additional agents within a single protocol.
We formed a working group with relevant stakeholders from clinical trials units, the pharmaceutical industry, funding bodies, regulators and patients to identify the main challenges of clinical trials. The working group generated ten consensus recommendations.
New regulatory routes for cancer treatment in the UK
Speed, robust quality, safety and efficacy standards are an important feature in drug development and patient access. The departure of the UK from the EU in 2020 resulted in the Medicines and Healthcare products Regulatory Agency (MHRA) becoming a standalone regulator.
This independence provided an opportunity to review the drug development and access pathway. We brought together a multi-stakeholder working group to compile a summary of the current status of the new regulatory approvals process.
The MHRA and the National Institute for Health and Care Excellence (NICE) offer independent and joint advisory services.
The MHRA offers a variety of services including their innovation office. They encourage early engagement, but you can seek scientific advice at any point in drug development with additional consultation available throughout the development programme.
In addition to the sponsors, patient representatives, trial site staff and other participants are welcome to attend these meetings. This may be particularly helpful for programmes involving novel or personalised trial designs.
NICE offers scientific advice and support through a Health Technology Appraisal (HTA). This is typically before the onset of Phase 3 trials but can be at all stages of health technology development.
NICE also provides the Office for Market Access (OMA) to life sciences industry partners. Stakeholders are identified during preparatory discussions and invited to engage in a structured and extended engagement meeting with the sponsor. These discussions will cover issues such as service delivery and commercial options.
Sponsors can engage at any stage of product development to gain insights to inform the development of their ongoing market access strategy. However, OMA engagement offers maximum benefit early in the market access and reimbursement process.
Joint scientific advice is available through the Integrated Scientific Advice service delivered by MHRA and NICE. The service provides a single, streamlined route for coordinated regulatory and health technology assessment advice during clinical development.
Sponsors can discuss their evidence-generation and clinical study plans at an integrated scientific advice meeting attended by MHRA, NICE and relevant experts, helping ensure alignment with both regulatory and HTA requirements.
Following the meeting, MHRA and NICE jointly prepare a single integrated report summarising their coordinated advice on scientific, regulatory and health technology assessment considerations.
The most significant of the new routes to market authorisation is the Innovative Licensing and Access Pathway (ILAP).
The ILAP is a pathway to support the safe, timely and efficient licensing and access to innovative medicines. It provides a single collaborative route for drug development, drug licencing and patient access.
Although Brexit was the main stimulus for the ILAP, elements of its design were inspired by other activities including the collaborative and multi-disciplinary RAPID C-19 initiative (Research to Access Pathway for Investigational Drugs for COVID-19) that was assembled to tackle the COVID pandemic.
Rather than being reliant on ad hoc support, the ILAP enables sponsors to obtain end-to-end integrated support from MHRA, relevant HTA bodies and other invited stakeholders.
Eligible medicines include, but are not restricted to:
novel chemical entities
advanced therapies
medicines for rare diseases
special populations
new indications for repurposed medicines
ILAP is open to both commercial and non-commercial sponsors based within the UK or internationally. It can support projects in very early stages of development or at mid-development stages.
To join ILAP, sponsors must complete an Innovation Passport application online. This will require brief information about the investigational medicine product (IMP) and its target patient population.
The passport is allocated to the IMP and a lead indication. Previous clinical evidence is not a requirement and applicants can draw from non-clinical models or other relevant models. Applicants will then be invited to discuss how their IMP fulfils the criteria, usually within four to six weeks.
The decision to award a passport is made by the ILAP partners within four weeks of this meeting.
Table 1: Criteria for obtaining an Innovation Passport
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Criteria 1: Details of the condition, patient, or public health area meet one of the following criteria:
a) The condition is life-threatening or seriously debilitating
b) There is a significant patient or public health need
Criteria 2: The medicinal product fulfils one or more of the following areas:
a) Innovative medicine such as an ATMP or new chemical or biological entity or novel drug device combination
b) Medicine is being developed in a clinically significant new indication for an approved medicine
c) Medicine for rare disease and/or other special populations such as neonates and children, elderly and pregnant women
d) Development aligns with objectives for UK public health priorities (Chief Medical Officer, DHSC or Life Sciences Sector Deal)
Criteria 3: Medicinal product has the potential to offer benefits to patients:
Requires a summary of how patients are likely to benefit, including improved efficacy or safety, contribution to patient care or quality of life, as compared to alternative therapeutic options.
After successfully obtaining an Innovation Passport, sponsors have to complete a target development profile (TDP) submission form. This provides more detailed information about the development of the IMP, foreseeable goals and challenges, and the amount of patient engagement required.
Sponsors are then invited for a meeting with ILAP partners to develop a TDP roadmap. The roadmap is jointly produced with the sponsor. This process will use appropriate tools from the ILAP toolkit to address any issues that may potentially hinder regulatory and access approval.
The TDP is designed to be a living document and will include a timeline and milestones as new information is added. This enables upfront descriptions of what is required from sponsors at specific stages along the development programme. The aim here is to expedite approvals and increase the likelihood of positive reviews from ILAP partners during the later approval steps.
Tools within the toolkit are listed on the MHRA website. There are currently eight tools available to sponsors to support development programmes to be regulation and access ready. Depending on the medicine and the sponsors’ position in the development programme, one or more of the tools in the toolkit can be used. Available tools include:
continuous benefit-risk assessment integrating real world evidence
access to recruitment populations via the Clinical Practice Research Datalink
