Real-world evidence is driving health technology assessments (HTA) in the UK, with 93 per cent of products reviewed by the National Institute for Clinical Excellence (NICE) in 2016 subject to ‘re-reviews’ within three years, according to consultants SVM Pharma in a briefing paper.
That means companies must collect additional real-world data on patient outcomes and submit it to the HTA authority if they are to retain its recommendation a product is reimbursed.
“Many positive submissions require a follow-up review two to four years later,” according to SVM. New clinical trials may be useful in some instances, but the cost and timescale often make them unattractive. “Real world evidence offers an exceptional alternative; after all what could be more supportive than real clinical outcomes, generated from within the patient population?” SVM says.
Regulators and HTA bodies are coming under increasing pressure to accelerate access to novel treatments that address unmet medical needs.
In response, the European Medicines Agency and national drugs regulators have put in place a number of schemes in which, once a product has shown safety and efficacy in phase II, it can get conditional approval, or access is granted for compassionate use, or it is approved for treating a patient sub-population.
This then allows companies to generate evidence using a drug or technology in a real world setting.
The HTA world is taking the same approach, recommending reimbursement on condition that companies then collect real world evidence to answer the most important question for health care systems, which is not that a product met its primary endpoint in a clinical study, but that it is effective in real patient populations, in specific healthcare settings.
Patients take centre stage
Mirella Marlow, Programme Director at NICE, says that not only are patients consulted by HTA agencies when devising guidance on new technologies, several products have been recommended on condition that specific outcomes data is collected and shared.
“For example, when NICE made a recommendation on the MiniMed insulin pump which contains sensors that monitor glucose levels, parents explained how concerns over their child’s diabetes were impacting on the rest of the family,” Marlow told Healthy Measures.
The need to regularly check children’s glucose levels around the clock, meant some parents had not slept through the night since their child was diagnosed with type 1 diabetes. This has a knock-on effect on all family members – including siblings who do not have diabetes.
“This is not something you pick up from reading a trial or reviewing the literature,” says Marlow.
Lay experts are sometimes more cautious than clinicians, particularly if existing diagnostics or treatments are good, but on other occasions will tolerate greater uncertainty and risk where the need is greatest. “We have very good experience of working with lay members of our committees: they can offer quite surprising insights; they are very thoughtful,” Marlow said.
For patients and carers, the attraction of the insulin pump with glucose sensors was the constant monitoring it promised. However, for NICE, the evidence on how the device might improve outcomes was not as complete as it would like. A compromise was reached: the device would be recommended for use, on the condition that more evidence is generated and shared by the manufacturer.
“The recommendation comes with specific requirements for further research,” Marlow says. For example, more data is being gathered on clinical effectiveness of the integrated sensor in younger children and pregnant women, and more health economic evidence is being generated.
Like many of the newer generation of diagnostics and devices, much of the data will be automatically generated by the technology in the real world. Rather than designing and implementing a controlled clinical trial, the manufacturer is allowed to market the device and collect outcomes data ‘in the wild’.
“The data reflects pragmatic real-life scenarios rather than in narrowly-selected clinical trial populations,” explains Marlow. “It answers real-life questions about how products perform over a long period or in patients living with several chronic conditions.”
This approach gives patients and payers access to technologies they value while additional data on long-term patient outcomes is collected or – for some devices such as cardiac pacemakers – how often batteries need to be replaced.
The information generated by connected devices is easily downloadable and, provided data protection standards are met, can be quickly shared with regulators and authorities without adding much cost to the industry. As transparency about outcomes becomes the norm, companies may also be incentivised by payment arrangements that adjust prices when patient outcomes are improved by a product.
Registries also play an important role in this new data-driven environment but HTA bodies want to ensure that data is of high quality, meets common standards, and is independently verified.
Marlow is working on a project in the EU-funded European network for health technology assessment (EUnetHTA), which aims to standardise HTA across Europe. “One of the new work packages aims to bring together a universal set of standards that HTA bodies and companies can use,” she says. “This builds on the PARENT (cross-border patient registries) initiative and would give everybody more confidence in the data collected by registries.”
HTA bodies, along with regulatory authorities, are just one of the forces moving healthcare inexorably towards a data-driven future. The key to making it all work will be linking patient outcomes data with other sources of information, according to Marlow.
“Data from registries and data collected directly from devices can be connected to hospital statistics and primary care data sets to give a much clearer picture of how patients fare,” she says. “As more sources of data become available it is increasingly important to be patient-focused.”
Know what payers value
In December NICE announced a collaboration with the US Food & Drug Administration to help developers of devices and diagnostics to generate the evidence needed to persuade payer and providers to approve reimbursement.
“In their efforts to get a product to market, companies can get caught out,” says Leeza Osipenko, who leads the NICE Scientific Advice programme, under which companies can get advice on how to set up trials to generate the evidence NICE requires in making its assessments. “They focus on safety data in order to secure the green light from regulators but, in order to get a product to market, they face new demands for data on clinical effectiveness and cost-effectiveness,” Osipenko said.
NICE will collaborate with the FDA Payer Communication Taskforce, which allows companies to get inputs from payers on how to design development programmes to produce the data needed both to obtain regulatory approval and to persuade the payers of the value of their product.
Similarly, in the EMA’s adaptive pathways scheme, companies can get joint advice from EMA and HTA agencies on how to design drug trials that will meet the evidence requirements of both. The scheme went live in April 2016 following a five year pilot.
During the pilot there was a high level of alignment between the EMA’s requirements and the national HTA bodies. Of the 31 parallel advice procedures, a single trial design was agreed that satisfied both EMA and HTAs in 70 per cent of cases.