Introduction

Antimicrobial resistance (AMR) is one of the most pressing global challenges we face this century. Already, AMR infections are estimated to cause 700,000 deaths each year globally. That figure is predicted to rise to 10 million by 2050 if no action is taken. The World Bank estimates that, across the globe, an extra 28 million people will be forced into extreme poverty by 2050 unless AMR is contained.

The UK Government’s 5-year action plan for antimicrobial resistance 2019 to 2024 includes the commitment to test solutions that address this issue, by evaluating and paying for selected antimicrobial products in a different way from other medicines.

To meet this commitment, NICE and NHS England ran a world-first pilot project, which paid companies a fixed annual fee for antimicrobials based primarily on a health technology assessment of their value to the NHS.

Building on the success of this pilot, between July and October 2023, NHS England held a consultation on proposals for establishing an antimicrobial products subscription model. Like the pilot, the subscription model will offer a contract with a fixed annual fee; that is, delinked from the volume of the product used. To qualify, products must meet the eligibility criteria and offer value for money to the NHS. The consultation also included the award criteria and scoring mechanism that the subscription model will use.

This thematic analysis report sets out a summary of the responses we received to the consultation.

Summary

We received 49 responses to the consultation. NHS England and NICE reviewed all feedback, grouping these into themes which best captured comments provided by respondents.

Engagement questions covered the following key features of the antimicrobial products subscription model:

• Route to commissioning
• Opportunities for companies to obtain clarification
• Award criteria and scoring mechanism
• Model contract

Respondents to the survey included representatives from the Association of the British Pharmaceutical Industry (ABPI), academic institutions, pharmaceutical industry, charitable foundations and other medical research funders, clinicians, private sector and patient groups, from the UK and globally.

Of the 49 respondents to this survey, 95.5% of respondents agreed with the overall purpose of the model (20% in agreement and an additional 75.5% in strong agreement).

Over 70% of respondents agreed with the overall procurement process outlined in the guidance on commercial arrangements for antimicrobial products and were highly supportive of the eligibility stage. Approximately 80% of respondents agreed that the eligibility criteria should be based on World Health Organization (WHO) priority pathogens.

Approximately 65% of respondents agreed with the opportunity for companies to obtain clarification, 16% did not agree. 12% were either indifferent or did not know.

Of those who responded to the awards criteria and scoring mechanism section of the survey, approximately 81% agreed that the 3 main categories describe the main areas of value.

There was more of a spread regarding whether the criteria in each category would allow for differentiation between products, with 45% supportive, 31% neither agreeing nor disagreeing, and 12% in strong agreement.

There was also a variation in responses to the scoring approach and to the attributed weightings for each criterion.

With regards to the model contract, over half of respondents agreed with the 4 value bands proposed for the contract, and a similar level of support for the contract length. Approximately 60% of respondents agreed with the key performance indicators on surety of supply and compliance with good stewardship practice.

Survey responses

Alongside the questions in the consultation, boxes inviting free-text answers were included. The themes raised by respondents in these boxes have been summarised below.

Purpose of the antimicrobial products subscription model

Harmonisation and alignment of initiatives

This theme was raised in 2 contexts: that pull incentives need to be designed to work in partnership with push incentives to make research and development for antimicrobials is well directed; and the need for the proposals by the UK for the subscription to work alongside schemes in other countries to achieve mutually desirable ends.

Scale of remuneration

One issue raised was whether the award amounts for each band was sufficient to encourage more research and development in antimicrobial products and that these would need to be reviewed to reflect changes in cost. There was also the suggestion that the amounts could be revised to reflect any developments in new models for the valuation of antimicrobials.

Antifungals and other categories of antimicrobials

Clarification was sought on whether the subscription model is open of all types of antimicrobial products, for example antifungals; and monoclonal antibodies for treating bacterial infections, bacteriophages and phage-derived enzymes, immunomodulating agents and microbiome-modulating agents – or just antibiotics.

Environmental standards

It was noted that the pilot model contract included the obligation to sign up to the AMR industry alliance on manufacturing standards.

Respondents raised the recent development of a BSI standard on manufacturing environmental standards and whether its inclusion in the model contract of the subscription model should be considered.

There was also a suggestion to include environmental standards in the eligibility criteria.

Risk management

Several respondents said the contract would not be deliverable if a spike in demand caused the cost of supplying the product to exceed the value of the contract. Clarification of a contract mechanism to address this issue was requested.

Route to commissioning – overall procurement process

Eligibility (pathogens)

There was general agreement that basing eligibility on the WHO priority pathogen list was appropriate to align global efforts on a pull incentive. Some suggested that this list should be flexible to account for other unmet needs, including UK-specific priorities (for example clostridium difficile, multi drug-resistant tuberculosis, stenotrophomonas maltophilia, nontuberculous mycobacteria).

Respondents argued that clinical eligibility criteria should evolve over time as priority unmet needs change, but that changes should be minimised to provide a consistent signal to companies in support of a stable long-term research and development strategy and successful pull incentive.

Eligibility (existing products)

Respondents welcomed allowing products already on the market to be considered for a contract under the subscription model in the first invitation to tender.

There was a suggestion that future tenders should not be limited to products that obtained UK marketing authorisation since the previous invitation to tender or are expected to obtain UK marketing authorisation within 12 months. New indications may be granted more than a year after initial marketing authorisation and products that were initially not eligible for the scheme may meet the criteria in the future.

UK-wide scheme

Many respondents welcomed the subscription model design within the consultation documents that would mean all 4 nations within the UK could take part in the scheme.

Limitation on volume of contracts

There was a positive response to removing the pilot limit of 2 contracts. A suggestion was made that where the NHS exercises the scheme mechanism to limit the number of contracts on offer in any given year, then any product not offered a contract should remain eligible to re-apply in future years.

Small and medium sized companies (SMEs)

The overall design of the procurement process should be mindful of SMEs, which should not be disadvantaged.

Frequency of tenders

Several respondents raised the issue of the appropriate frequency for issuing the call for additional contracts and whether approximately once every 12 months was correct. For example, some suggested it should be “open” so that consideration of a product would be a rolling programme to match the granting of marketing authorisation

Length of contract

The subscription model lasting for up to 15 years to cover the intellectual property exclusivity period of the product was broadly welcomed.

However, concerns were raised that an initial contract period of 3 years with extensions may provide insufficient certainty for investors to commit to the research and development needed to bring products to market.

Pipeline or qualification designation

A suggestion to support the ability to raise funding for research and development was the introduction of a qualification designation for products likely to qualify for a contract, like the existing qualified infectious disease product (QIDP)/priority medicines (PRIME) designations in the US/EU.

Transparency

Some respondents argued for more transparency in the decision-making process, for example requesting that we publish membership of the eligibility assessment panel and evaluation panel.

Others argued for more confidentiality, and disagreed with the proposal to publish full information on the organisations awarded a contract, including the value band, scores and an account of the evaluation panel’s rationale.

Route to commissioning – opportunities to obtain clarification

Dialogue stage

Respondents raised the issue of whether a dialogue stage as used in the pilot could be retained for the UK subscription model

Evidence clarification process

If a full dialogue stage is not incorporated in the design of the subscription model, respondents were asking to have a clear step in the process where they would be able to understand and discuss the evidence submitted.

Participation in award panel meeting

An additional suggestion was that applicants would be able to take part in the award panel meetings.

Patient population

Respondents felt there was a need for applicants to be involved in any process that scopes the patient population for which a product will be assessed at the later award stage.

Award criteria and scoring mechanism

Scoring process

There was some concern that the procurement process is too mechanistic and inflexible for the award stage, with too little discretion from the evaluation panel. One respondent suggested proposed weights could be defaults to be varied with justification by the panel; an approach not permissible under public contract regulations.

Updating the award criteria

Stakeholders welcomed the proposal that the award criteria would be reviewed and refined over time to ensure they continue to remain relevant to global and UK unmet needs.

Overlapping criteria

Some respondents suggested that some of the award criteria overlap, that is capture the same aspects of product value, and so the scoring system could overvalue or double count the overlapping aspects.

Some questioned whether the criteria would provide meaningful differentiation between products.

Spectrum, transmission, enablement, diversity and insurance (STEDI) values

Respondents were satisfied that the award criteria adequately capture the five STEDI values that reflect the additional value of antimicrobials compared with other therapeutics. However, some suggested that transmission value was not well represented.

Some respondents argued that the scoring system may disadvantage narrow spectrum agents that target 1-2 pathogens only, unless they address a high unmet need.

Value missing from criteria

Respondents had different opinions on if and how the award criteria should reflect the target population size and whether the criterion on unmet need sufficiently captures the clinical value of antimicrobials.

Several respondents recommended refining specific criteria to ensure the level definitions and evidence requirements are clear, relevant and objective (for example, infection site penetration and reduced collateral damage).

Defining toxicity

Respondents suggested that evaluating all-cause serious adverse events will disadvantage products that treat the sickest patients with more comorbidities and higher rates of serious adverse events.

Some suggested that adverse events could be defined relatively compared with the best alternative therapy, instead of in absolute terms; but recognised it would be unrealistic to provide statistically powered comparative evidence from resistant infections.

Attainability of criteria

There was concern that it would be difficult to achieve higher-scoring levels on the criteria on cross-resistance, rapidly emerging resistance and relative effectiveness. For mode of administration, top levels could be unattainable for intensive care unit-delivered antimicrobials.

Evidence requirements

Some respondents were concerned that the standards of evidence to support meeting the criteria are high, and some might not be available at the time of marketing authorisation.

This is particularly the case for relative effectiveness, where the requirement for clinical trial evidence in resistant infections was considered unattainable because the prevalence of resistant infections is too low to provide enough statistical power, and hospital length of stay, which is not routinely collected in clinical trials.

Respondents suggested permitting alternative sources of evidence, including expert clinical opinion and more international data.

Model contract

Fairness and consistency across 4 nations

A small number of respondents noted that payment amounts for the value band ranges were not stated, and so urged consistency in scoring, fairness and success across the 4 nations.

Comments from respondents suggested that the current text of the subscription model scheme implies companies can decline contracts in one or more of the 4 nations and that this may lead to cherry picking of the most lucrative market (England). Respondents suggest it should be a requirement for companies to supply all 4 nations of the UK (if the devolved governments of those nations opt to participate).

Supply

Many respondents raised surety of supply. They were supportive of the indicators and advocating for strong supply contracts and enforcement; but expressed concerns about the number of months of stock, particularly for small and medium sized companies. Reasons noted included limited shelf life, subsequent wastage, impact of Brexit, risk of supply to other markets in need and lead times for manufacture and delivery.

There was some concern from respondents that the subscription model was only accessible to large pharmaceutical companies, as maintaining stock due to limited finances may be a blocker for many SMEs.

Clarity was sought by respondents as to how applying organisations should demonstrate “capacity” in this context (for example, is there an expectation to evidence supply contracts between developers and manufacturers or manufacturing slots?).

Clarity was also sought as to what flexibilities (if any) will be provided with these supply requirements.

Environment

Many responses raised the environment standards as a contractual requirement, and requested clarity on what ‘demonstrate compliance’ would mean in practice.

One suggestion was to add “for example, by reference to BSI ‘Minimized risk of antimicrobial resistance’ certification to the [AMR Industry Alliance] standard ‘minimizing risk of developing antimicrobial resistance and aquatic ecotoxicology in the environment from the manufacture of human antibiotics’.”

Length of contract

Responses here were mixed. Some state the length strikes a good balance between establishing meaningful progress and allowing for flexibility in response to evolving circumstances.

Others believe 3-year contracts were too short, unless there are safety profile concerns, and that a 10-year contract would be necessary for the UK fair share to be reached.

Another group queried whether the contract period is too long and disincentivises continuous innovation throughout the lifespan of a contract.

Many respondents queried how any contract termination would be triggered and managed. Clarity on whether a notice period would be implemented, if the contract would include flexibility for both parties or unilaterally for the NHS only, would there be full re-assessment by committee, and would there be an option for an appeals process.

One respondent was worried that the subscription model contract might cause confusion of uncertainty for generic manufactures. They suggested a requirement for a company to commit to the loss of exclusivity date would help generic companies to be prepared for entry.

Respondents raised the point that that the contract duration should be extended to cover any exclusivity extensions resulting from a paediatric investigation plan, ensuring that scheme also incentivises companies to expand into the paediatric space.

Value bands

Many respondents suggested that the points-based thresholds for the value bands are too ‘simple’ and there is a risk of devaluing products that may meet need.

Many also felt that the value bands are too ambitious and very few products will reach the higher band.

Feedback included a suggestion to offer a range rather than fixed amounts, this would also mirror the scores provided as ranges.

Refreshing contract and future proofing

Feedback throughout sought clarity on a ‘renewal and review’ process at time increments, to ensure approved products are still fulfilling the requirements, and so the model reflects future AMR risks. This would offer an opportunity to review emergence of resistance and avenues for de-listing should it be required. There were requests to detail the triggers and timelines for re-assessment of products.

Respondents felt key performance indicators should remain adaptable to changes in evidence and industry practices to ensure ongoing effectiveness. Suggestions were also made to include an additional indicator to ensure companies already locked in and awarded a contract would be continuously innovating.

Defining good stewardship

Requests were made for further clarity on how good stewardship practice is defined and compliance measured within the NHS, and to add further contractual provisions on global stewardship and access.

Other

A number of comments were raised about the potential to include a requirement in the model contract for companies to ensure access of the antimicrobial products in low and middle income countries.

The issue of wastage minimisation was raised. The example given was a situation where companies would be unlikely to accept any returned goods from outside of supply chain quality process. The respondent suggested clarity was required to confirm how this will be managed in practice, to ensure no wastage of critical antimicrobials.

Equality

All NHS England consultations ask the following question on equality:

The key emerging themes in response to this question in the consultation fall into the following 3 areas:

1. The importance of ensuring the model supports development in areas with particular unmet need across demographics and health conditions; with additional criteria to assess efficacy and eligibility to support and improve diversity and equality.
2. Using and taking into account demographic data when considering the impact on patients and environmental setting (for example, the demonstrable increase in carriers of multidrug resistant Gram negatives in urban areas associated with social deprivation).
3. Consideration for pharmacokinetics, pharmacodynamics and safety data plans in paediatric patients, and ensuring studies are completed.

Publication reference: PRN01167