Why earlier access requires earlier dialogue

TOPRA’s latest informal roundtable discussion – Parallel Scientific Advice with MHRA and NICE: what are the advantages and how does it work best? – took place on 24 September at the Royal Society in London. The discussion on parallel scientific advice, chaired by Dr Nick Sykes (Pfizer), attracted 25 senior TOPRA members and external guests who debated the workings and effectiveness of MHRA and NICE advice procedures available to companies developing new medicines.

An overview of Product Specific and Broader Scope Scientific Advice procedures from the MHRA was given by the Agency’s representative Dr David Wright. It was highlighted that with both procedures a face-to-face meeting would be held with MHRA to discuss the company’s questions, but that formal written responses to the questions would be provided as part of the Product Specific Scientific Advice process but not as part of the Broader Scope Scientific Advice procedures.

This approach has arisen largely because the Broader Scope Scientific Advice procedure had been introduced as a more informal way for companies to obtain more general advice on issues which could affect a number of different products in development (eg, general manufacturing process changes not restricted to a specific product). Therefore the issue of formal advice letters was considered inappropriate.

The MHRA Early Access to Medicines (EAM) scheme, launched in April 2014, was also presented to show the mechanisms for making new medicines available to patients before a Marketing Authorisation (MA) is granted. Inn order to make a product available under this scheme two steps must be completed.

  • Step 1 is to obtain Promising Innovative Medicine designation which is generally granted on the basis of Phase I/II data.
  • Step 2 is to obtain an EAM Scientific Opinion from the MHRA based on the Phase III data submitted at the time of MA application. This EAM Scientific Opinion would be published on the MHRA website and, assuming it was positive, enable the medicine to be supplied before the MA is granted.

This prompted interesting discussion around the utility of the EAM scheme and the fact that the medicines could not be charged for or promoted – therefore what was the mechanism was to facilitate patient access? It was clarified that NHS England was likely to have a role and that the exact mechanism would be further defined over time as this still a relatively new procedure.

Dr Leeza Osipenko (NICE) outlined the role of NICE in the review of innovative medicines and its role in decisions on whether these products were recommended for funding by the NHS. It was highlighted that where the regulators (eg, MHRA) make an assessment of the products efficacy – ie, does the product have the therapeutic effect as demonstrated in clinical trials – NICE is interested in effectiveness – ie, what is the product’s impact on clinical practice in comparison to other products – and efficiency, ie, whether it is cost effective and makes efficient use of NHS resources.

These assessments are made by a committee including patient and clinical experts, and while the end of the appraisal process itself occurs generally 3-4 months after grant of the MA, the process itself starts about 5-6 months before the MA is granted. There is an opportunity for discussion of the appraisal process and submission package at a Scoping Meeting, generally held 12-18 months before the process starts, however NICE strongly encourages companies to request and participate in a Scientific Advice meeting before the start of Phase III. This allows companies to understand what NICE expects to see in a Phase III study design before it is started so that changes can be made if required. In addition to discussing questions related to the trial design, eg, choice of comparators, endpoints or duration of the study, questions can also be raised regarding the economic evaluation, such as plans for which economic models will be used.

Dr Wright concluded the presentations by discussing the joint MHRA/NICE Scientific Advice procedure which is available. This joint procedure has been developed in order to help industry design Phase III studies to meet the expectations of both MHRA and NICE. It was highlighted that throughout the procedure there are extensive interactions between MHRA and NICE, and they will discuss their respective draft advice letters to try to reduce inconsistencies/conflicting advice between the two agencies. It was also discussed that use of this joint national procedure was a useful step before a joint EMA/HTA meeting where regulatory and payer advice could be sought at a centralised level.

Then the floor was opened up for the discussion. It was apparent that NICE has a desire to get more involved with companies at an earlier stage in order to provide input into the drug development process and to build closer links with the regulatory personnel in development companies. For example while it was generally seen as an obvious part of the development programme to obtain MHRA buy-in to study designs it was not automatic that NICE should be approached.

There were also a feeling that companies should increase dialogue between the groups/personnel responsible for market access who would traditionally interact with NICE and those responsible for regulatory who would traditionally interact with MHRA.

Report by Leigh Shaw MSc MTOPRA, Director, GFA

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