Real World Development: Increasing value for patients
pharmafile | June 30, 2010 | Feature | Research and Development |Â Â Kinapse, drug developmentÂ
The traditional drug development paradigm is protracted and costly, with many products failing to deliver commercial or clinical success.
We propose a fundamentally new approach – Real World Development – which constantly assesses a product in as close to post-marketing use as possible, utilising adaptive trial design and capitalisation of existing real world data sources. It enhances the evaluation of benefit/risk, enables earlier access to innovative medicines and improves value for money.
To realise this approach, we have built a detailed financial model supporting the design and funding of a Real World Development (RWD) programme and associated decision-making process.
Drug development today is unsustainable
The drug development model has remained relatively unchanged for two decades, a well-trodden path from pre-clinical R&D to extensive phased clinical trials, and a launch with post-marketing vigilance activities. Notably, phase III pivotal trials carry the highest costs in the cycle; they are designed to demonstrate clinical effectiveness and an acceptable benefit/risk profile prior to regulatory submission. Moreover, securing Health Technology Assessment (HTA)/Health Economics Programme (HEP) support is critical to establishing the economic viability of a new drug. But, this takes place late in the development cycle (after regulatory filing and/or approval), further delaying the time to market.
The current situation is commercially and clinically unsustainable, and the future of the innovative pharmaceutical industry is genuinely under threat.
Changing development for the real world
The underlying principle of the RWD approach (Figure 1) is to profile clinical benefit and economic value of innovative medicines in carefully monitored ‘real world’ settings. This approach acknowledges that new drugs must demonstrate benefit to patients in a real world setting, a context that phase III clinical trials cannot suitably emulate.
Confidence of clinical efficacy (CoCE) is demonstrated from a lean phase IIIa double-blind randomised clinical trial, sized for demonstration of efficacy. Parallel simple trials establish real world value for specific patient populations in respect of clinical efficacy, safety, risk/benefit (Confidence of Benefit, CoB) and economic value (Confidence of Value, CoV).
The main features of RWD include:
• Greater patient focus, allowing earlier access to innovative products
• Drug application in a real-world setting (demonstrating CoCE and CoB)
• Earlier and better characterisation of risk, helping support decision-making
• Adaptive trial design accommodating emerging ‘in-stream’ clinical data
• Existing real world data utilisation (e.g. observational data sets, electronic medical records); and
• Eliminating traditional hypothesis-testing clinical trials in phase IIIb and/or phase IV.
The approach supports earlier decision-making based on near real-time information in the interests of public health, further supported through a shared understanding by stakeholders including payers, regulatory authorities, HTAs, patient advocacy groups and physicians. Critically, it strengthens patient safety through ongoing monitoring of exposed patients. Standards for patient eligibility and consent are maintained, with reassessment of eligibility criteria as the data set expands.
Drugs most suited for the RWD approach include those for which the target patient population is discrete or limited, including end-of-life drugs, rare cancer treatments and orphan drugs. RWD enables investigation in a commercially and clinically risk-contained environment.
Implementing real world development
RWD builds on existing precedents, including adaptive trial design (as approved by the FDA), and conditional approval of products. Similar models have been explored and tested in other jurisdictions.
Adaptive trial design allows studies to undergo in-trial modification that enables exploration of promising developments. This accommodates interim evidence of the benefit/risk of the product being assessed and encourages exploration of stratified patient populations where initial benefit is observed. Early termination of a trial can be explored if clinical efficacy is not demonstrated or safety issues are identified, reducing the risk of harm and/or downstream expense.
In Europe, the European Medicines Agency Committee for Medicinal Products for Human Use (EMA CHMP) can conditionally approve innovative medicines for up to one year. The US FDA grants similar accelerated approvals, with no validity period.
Enabling processes and technologies include in-stream working with clinical study data sets, extensive utilisation of electronic data management approaches, and direct analysis of high quality electronic medical records (EMR).
Improving the economics of development
The traditional development model also suffers from inherent uncertainty because of the late characterisation of clinical, regulatory and commercial risks. The RWD approach can obviate these risks and deliver a commercially viable outcome.
To support the financial case, Kinapse has developed a proprietary data-driven model to investigate the economic benefits of this new paradigm.
The main features of our model are:
• Assessment and evaluation of individual trials based on real world data
• Utilisation of standard costs, cycle times, attrition rates and sales curves generated from public sources, or sponsor data
• Incorporation of customisations (e.g. clinical trial cycle times, costs, patient numbers, etc.)
• Rendering alternative RWD scenarios
• Application of changes to clinical trial times, costs, patient numbers etc. Along with;
• of cash flow profiles and programme valuations.
Indicative modelling has substantiated the benefits of RWD accruing from:
•Earlier product commercialisation, with resultant earlier sales and longer patent exclusivity period
• Leaner phase IIIa pivotal trial to fund parallel real world methodologies; and
• Reduced overall development, marketing and sales expenditure.
Getting started
Building on our financial model, we have developed a pilot approach to initiate a RWD programme. The components of this pilot are:
• Programme profiling to identify suitable studies for RWD
• High-level programme design such that it enables stakeholder discussion
• Stakeholder management to secure internal and external stakeholder agreement of the programme design; and
• Programme execution in a ‘learning lab’ approach, whereby lessons from the pilot inform subsequent trial design.
Our analysis suggests RWD approaches are best applied to programmes that:
• Are regionally focused (simplifying regulatory/HTA organisation co-ordination)
• Have modest clinical/operational risk
• Bear limited commercial risk; and
• Allow contingencies should reverting to a traditional model be required.
Conclusion
The adoption of RWD on a large scale requires strategic and operational challenges to be addressed. At Kinapse, we believe the potential benefits of this strategy are substantial, and we continue to develop our RWD model in conjunction with industry stakeholders. We welcome ongoing dialogue with all stakeholders to bring about this model for drug development.
Shanaka Thilak, Consultant, Andy Black, Co-founder and Global Head of Client Services. Stuart Pavelin, Vice-President and Lead, Asset Value Consulting practice. Website for more info/contact: www.kinapse.com
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