Impact case study database

From 2016, DMU’s research-based methodology to objectively assess nonadherence to medications progressed from the laboratory to clinical application in hospitals in Iraq and Kenya. In doing so, it optimised treatment plans for patients with cardiovascular disease and improved clinical outcomes; led to changes in clinical practice to improve medication adherence; and raised the alarm for the circulation of poor-quality or counterfeit drugs within the Kenyan health system [C1-C4].

(1) OPTIMISING PATIENT TREATMENT PLANS AND IMPROVING CLINICAL OUTCOMES

The Al Sader Teaching Hospital and Misan Cardiac Centre in Iraq were the first in the world to implement DMU’s DBS microsampling test in a clinical environment, targeting patients with heart disease. Iraq is widely recognised as experiencing a high burden of cardiovascular disease relative to global averages. A 2018 article in International Journal of Public Health ( https://doi.org/10.1007/s00038-017-1012-3) demonstrated that the age-standardised, disability-adjusted life years rates in the Eastern Mediterranean Region are considerably higher than the global average, while Iraq has the second highest CVD death rate in this 22-country region.

In 2019 Tanna trained healthcare professionals in Kenya in collecting, storing, transporting and preparing DBS samples for analysis at DMU. She hosted workshops to facilitate knowledge transfer with partners from both hospitals in Kenya. Use of the DMU blood test in Kenya was seen, in part, as a way to identify whether non-adherence to CVD drugs might be attributed to the sale of poor quality, unregistered or counterfeit medications to patients [C4]. According to the WHO (https://apps.who.int/iris/bitstream/handle/10665/326708/9789241513425\-eng.pdf?ua=1\), 42% of all fake medicines reported to them between 2013 and 2017 were from Africa.

Analysis of close to 600 patient DBS samples from both countries provided the first clear evidence to clinicians in Iraq and Kenya of the extent of medication nonadherence among patients with heart disease [C1–C4]. The findings on blood drug levels for each individual patient revealed that 285 patients (148 in Iraq and 137 in Kenya) were nonadherent to one or more of their prescribed cardiovascular drugs. Through discussions with patients to establish possible reasons for nonadherence, clinicians were able to make informed decisions about changes to medication and to develop more personalised patient treatment plans, for example decreasing the complexity of prescribed dosing regimens [C2, C4].

This is a significant improvement on previous practice where the approach was simply to increase the dose or add another medicine to the prescription for patients with poor symptom control [C2, C4]. At KNH, where the highest percentage (51%; n = 122) of heart disease patients were found to be nonadherent to prescribed drugs, the lead clinical pharmacist said subsequent changes to treatment plans had ‘decreased the risks of cardiovascular events’ for patients, ‘impacting positively on patient’s social economic standing due to adherence to medication’ [C4]. He said ‘medical doctors greatly benefitted’ from DMU’s research as it provided them with the evidence base to change the healthcare plans of these patients. This resulted in ‘decreased emergency hospital visits due to spiking blood pressure’ and a ‘better quality of life for the patient’ [C4]. Clinicians reported positive changes in patient behaviour in terms of taking their medications as prescribed, resulting in enhanced compliance [C2, C4]. The lead cardiologist at Misan Cardiac Centre in Iraq said: ‘As the data were specific for each patient and for each medication in the collected Iraqi sample, I reacted to each case of non-adherence individually and started checking the treatment plan with consideration of patient perspective’ [C2].

(2) CHANGING CLINICAL PRACTICE TO IMPROVE LONG-TERM MEDICATION ADHERENCE

The research findings led KNH to change its clinical practice by formally embedding pharmacists, nurses and hospital-based social workers within the clinical teams [C4]. Pharmacists now play a pivotal role in carrying out regular medication therapy management and in educating patients on the importance of adhering to prescribed drug therapy [C4]. Nurses educate patients on the need to frequently monitor blood pressure and social workers are now used to provide counselling and direct patients as to where they should go to obtain their medication [C4]. There have been fundamental changes to KNH patient treatment plans, including reductions to patients’ pill burden and a decrease in polypharmacy, which boosts adherence and reduces costs [C4]. The packaging of medicine has also been improved to enable the elderly to take their medicine correctly without confusion [C4].

At Misan Cardiac Centre, the role of clinical pharmacists in the medical team has been strengthened; they now communicate with patients on the importance of adhering to prescribed drug therapy [C2]. The Centre recognised the wider applicability of the DMU test in the assessment of medication adherence for other chronic diseases in Iraq such as diabetes [C2].

(3) IDENTIFYING HIGH RISK OF SUBSTANDARD OR COUNTERFEIT MEDICINES IN THE KENYAN HEALTH SYSTEM

DMU’s research findings raised a critical healthcare issue: further evidence of the high risk of poor-quality or counterfeit drugs circulating within the Kenyan healthcare system and unknowingly being made available to patients [C3, C4]. This came to light because DMU’s research findings revealed that 117 (49%) of the KNH patients, who appeared non-compliant based on the DMU analysis, had in fact taken their medication. However, the drugs could not be detected in their DBS samples. This was seen as an alarming finding and confirmed suspicions raised by clinicians over the poor quality of particular drugs that were being supplied [C4].

The consultant clinical pathologist at AKUH concluded: ‘The absence of detectable levels of these drugs in patients who reported that they were compliant is concerning given that one of the possible explanations could be substandard medication’ [C3]. The clinical pharmacist at KNH wrote [C4]: ‘The DMU results have now highlighted the possible existence of such poor-quality medications in circulation within the health care system in Kenya and confirms suspicions raised by some clinicians on the poor quality of particular drugs supplied. Clinicians have previously noted that different brands of drugs elicit different responses.’

The DMU results revealed that different brands of prescribed cardiovascular medicines gave different results with respect to blood drug levels. As of the end of the impact period, suspected brands were under investigation; the research findings have informed the choice and brand of cardiovascular medication stocked in the KNH pharmacy department [C4]. KNH’s clinical pharmacist reported in December 2020 that the matter had been taken up by the national regulatory body. He wrote:

The matter of poor quality, unregistered drugs in circulation is now being reviewed by the Pharmacy and Poisons Board within the Ministry of Health in Kenya that oversees medicines safety. This is with a view to adopting further policies to address bad practices and the sale of poor-quality, unregistered or counterfeits medication. This will be monitored by the pharmacovigilance authority that follows up on complaints due to medicines and submits their reports to the regulator. [C4]

The collection and analysis of high-quality linked data, led by Harris at DMU [C1], made it possible, for the first time, to compare the care that maternity units provide to women in Britain. The evaluation, the largest of its kind, identified priorities for improvement in care, where unexplained variation in outcomes for women and babies exist, identified areas of good practice and detected gaps in policy and guidelines. Harris led on a strategy to engage the midwifery community in the findings and drive quality improvement with published articles in Midwives, the RCM’s magazine (48,000 members), and Midwifery Matters, and presenting at conferences. Evaluation findings are freely accessible to healthcare professionals, policymakers and members of the public via the NMPA website (www.nmpa.org.uk\). For the first time, units in England, Scotland and Wales are comparing their risk-adjusted findings with those of others and against the national mean to take action accordingly.

(1) BETTER CARE OUTCOMES FOR WOMEN AND BABIES

The research identified a significant percentage of NHS Trusts/​Boards as potential outliers for one of three measures (>3 SD above the mean): PPH (18%), Apgar score (13%), third- or fourth-degree perineal tear (14%) [R4]. A quarter of all Trusts/​Boards (38 out of 155) said they had reviewed their local data following the 2017 clinical evaluation [R4] and conducted case note reviews and internal audits [C2]. Fourteen services carried out staff training and 21 undertook formal investigations into cases or systems, demonstrating the powerful impact that the research has had on quality assurance processes to drive improvements in care [C2].

Fifty-one services volunteered as case studies to present the work they had done in response to the findings in R4 and the effect this has had on clinical measures. There is clear evidence from testimonials that changes in practice as a result of the research have improved care for women and babies. Northampton General Hospital reports that, following implementation of an action plan, the percentage of women experiencing a PPH of 1500ml or more was reduced by more than one-sixth, or 0.7 percentage points, from 4.1% to 3.4% by September 2018 [C3]. Stockport NHS Foundation Trust implemented the Stockport Perineal Care bundle and reported a reduction in the incidence of severe perineal tears [C4]. Yeovil District Hospital NHS Foundation Trust reported a significant improvement in PPH rates following their response to the clinical evaluation findings, which included improvements in calculating blood loss accurately, documentation and multidisciplinary training [C4].

Data collected as part of the second organisational survey [R3, C5] found that NMPA data had been used to make improvements in the organisation of care within Trusts/​Boards (59% of respondents) in collaboration with Local Maternity Systems/​networks (32%). Services also used the data to inform women about their services (15% of respondents), to guide local audit (50%) and to make improvements to data (44%) [C5].

(2) IMPROVED MATERNITY DATA CAPTURE AND QUALITY

Many services contacted Harris and other members of the research team to request additional support on how to improve the quality of their data, as a direct response to concerns around missing data that were identified through the research [R4]. This led to alterations in data fields in local Maternity Information Systems as well as the flow of data through the local system before reaching national initiatives like the NMPA. Data capture improved from 92% in the 2017 clinical report to 97% for the 2019 Clinical Report with a similar improvement in data capture of individual items [R4: 11, R6: xi].

(3) INCREASING AWARENESS OF UNEXPLAINED GEOGRAPHICAL VARIATION IN MATERNITY CARE OUTCOMES AND EMPOWERING INTEREST GROUPS TO PUSH FOR FURTHER IMPROVEMENTS

NMPA advisory groups include third-sector groups and members of the public; advice and support are provided by the Women and Families Involvement Group. The NMPA findings have been published in user-friendly reports on its website, which are designed to inform women’s choices over where and how to have their baby. The website has seen 10,100 new users and more than 99,000 unique page views[C6]. The average time spent on the site is five minutes, with an average of six pages viewed, indicating high levels of engagement with the data. Users are predominantly based in Great Britain (78%) but there is significant interest from the USA (6%), China (5%) and other countries (11%), illustrating the data is relevant to the international maternity community. This is supported by the research literature; for example, Souter et al (2020, https://doi.org/10.1097/01.AOG.0000663696.09421.af) have benchmarked outcome measures in a US birth cohort against those published by the NMPA. The website has seen significant spikes in visitors coinciding with the publication of key reports (and accompanying media coverage [C5]), with 200% increases in weekly traffic [C6].

Both the 2017 and 2019 clinical reports received significant media coverage in the UK [C5]. Upon publication of the 2017 findings, the BBC reported on calls from the RCOG to investigate unexplained variation, quoting its president as saying: ‘We urge all maternity units to examine their own results and those of their neighbours both to identify role models and to drive quality improvement locally’ [C5,p4]. A Guardian article [C5,p2] highlighted a finding that fewer than one in six women who give birth every year sees the same person throughout her pregnancy and aftercare, despite promises that this should happen. It quoted a senior policy adviser at parenting charity NCT as saying that the research ‘reveals a number of problems including staffing shortages that puts safe care at risk, and postnatal care that often leaves mothers struggling alone’.

The clinical findings published in 2019 [R6] reported that the proportion of pregnant women overweight or obese had risen to more than half for the first time (50.4%), and increasing risk of miscarriage and stillbirths, was covered widely [C5]. The Daily Telegraph quoted the director of the National Obesity Forum as saying the figures were ‘hugely depressing’ and calling on the UK Government to do more to ensure the risks of a high BMI were taught to girls in schools [C5,p5]. The 2019 Clinical Report was widely reported across local news media to highlight regions in which there were concerns around care outcomes. For example, Wigan Today reported that women who give birth in Wigan were more likely than average to suffer serious blood loss; it also gave the Wrightington, Wigan and Leigh NHS Foundation Trust the opportunity to clarify that the Trust had bettered the national average for 10 of the 13 NMPA clinical outcome measures [C5,p5].

(4) INTEGRATION OF CLINICAL MEASURES INTO DATA STRATEGIES AND CHANGES TO MATERNITY REGULATORY AND POLICY PROCESSES

Harris and the project team have worked closely with national dataset teams, regulators, clinicians and service providers to share learning related to data collection and quality. NHS England has acknowledged that the study programme acts as ‘an important benchmark for local areas, helping identify where improvements can be made, including ensuring the right staffing levels for the women and babies they care for’ [C5]. Crucially, three of the 16 clinical measures in R4 (PPH of 1500ml or more, low Apgar score and third/fourth-degree perineal tear rates) were adopted as quality improvement metrics by NHS Digital’s Maternity Dashboard, a dataset that helps maternity teams improve their clinical outcomes, and which was set up in 2016 in response to NHS England’s ‘Better Births’ five-year vision [C7]. Study findings have also influenced the development of new metrics for Version 2 of NHS Digital’s Maternity Services Dataset (MSDS), a patient-level dataset that captures information about activity carried out by maternity services in England [C8]. Another HQIP-funded programme is the Confidential Enquiry into Maternal Deaths in the UK. A November 2019 report from this enquiry endorsed the following NMPA recommendation, which was published in [R5]: ‘data gathering on maternal critical illness should be re-examined and strengthened by new definitions in order to capture lessons about good care and near miss events’ [C9]. The research team shared its ‘outlier’ findings with the Care Quality Commission (CQC). As a result, CQC uses NMPA metrics in its regulatory process [C10]. This ensures maternity services are held accountable for their findings and called to respond as appropriate, with action or justification for results that are unexpected.

Studies at DMU highlighting the generation of potentially harmful toxins through the exposure of PUFA-rich cooking oils to high-temperature frying have informed the food industry’s development of alternative oils that do not readily oxidise to ingestible toxic aldehydes under thermal stress, and an increased public awareness and understanding of this health risk.

(1) PROVIDING THE EVIDENCE BASE FOR THE FOOD INDUSTRY’S DEVELOPMENT AND MARKETING OF ALTERNATIVE COOKING OILS

The UK’s Department for International Development funds the Supporting Indian Trade and Investment for Africa (SITA) project, an Indo-Africa trade partnership that aims to build the export capabilities of industries in five East African countries. As part of its efforts to support the development of the sunflower oil sector, SITA commissioned the East African virgin sunflower oil study that led to the publication of R3. The results benefited sunflower oil processors, industry associations and regulatory authorities in Tanzania and Uganda, who found themselves ‘in a better position to improve services to their stakeholders’ through the verification of the quality of their products’ [C1]. According to SITA, several sunflower oil producers from these countries, i.e. millers from farming regions, said the research findings support ‘export readiness for EU markets’. It commented: ‘Export preparedness and exposure to international markets is vital to ensure sustainability of the sector’ [C1].

Thrive Algae Oil ® is a MUFA-rich culinary oil produced from algae – the first of its kind on the market – that was originally developed and manufactured by American company Solazyme. It is available in US-based retailers such as Whole Foods, Walmart and Amazon. The product was acquired by large Dutch food and biochemical company Corbion in 2018, who made a strategic decision to extend the sale of Thrive Algae Oil to the business-to-business environment. Grootveld’s Nature Scientific Reports paper [R2] ‘formed the basis for marketing material for Thrive Algae Oil’s push into the B2B space’, as confirmed by the former Head of R&D for Solazyme and consultant for Corbion, who also stated that ‘Professor Grootveld’s seminal paper on toxic aldehydesi in frying oils was a pivotal contributor to our decision to engineer an oil high in MUFA (≥94%) and low in PUFA to minimize the generation of toxic aldehydes during frying events’ [C2].

Similarly, the research in BMC Research Notes [R5] reported the favourable peroxidative resistivity of naturally-fermented cod liver oil products marketed by US company Green Pastures Products. The company’s General Manager of Production and Quality Assurance stated:

The finding of this project reveals the unique properties of our products and provides the scientific evidence of the benefits of fermented cod liver oil. The results have been used to improve our production processing, including extending the fermenting period to increase the yield and adjusting the storage condition to help save cost … A professionally-prepared Health and Medicine Research Outreach article … and podcast based on these findings, which was sent to dozens of our wholesalers, facilitated the dissemination of beneficial product information to thousands of customers. We anticipate at least a 5% increase in sales will be achieved after the results are broadcasted to our wholesalers and retail customers in this quarter [C3].

(2) INCREASING PUBLIC AWARENESS AND UNDERSTANDING OF HEALTH RISKS ATTACHED TO FOODS FRIED IN PUFA-RICH COOKING OILS

Since June 2014, Grootveld has proactively engaged with the media, food organisations and high-profile chefs to increase public awareness and understanding of the potential health risks of frying foods in PUFA-rich cooking oils. In 2015, Grootveld ran a series of experiments for the popular BBC documentary series Trust Me I’m A Doctor, which were designed to determine which oils are best to cook with. The analyses found that the PUFA-rich oils, like corn oil and sunflower oil, generated very high levels of aldehydes in contrast to the oils and fats rich in saturated fats or MUFAs (like butter and olive oil). Grootveld identified two previously unknown aldehydes that had not been seen in other oil-heating studies. Based on the study’s conclusions, later published in R1 and R2, the programme’s presenter, Dr Michael Mosley, communicated three main recommendations to an estimated 3,000,000 viewers in the 29 July 2015 episode [C4]:

• To reduce aldehyde production when cooking by choosing an oil or fat high in monounsaturated or saturated lipids and low in polyunsaturates, with olive oil representing a good compromise.

• Minimise the amount of oil use when cooking.

• Keep oils tightly sealed in a cool, dry cupboard to prevent oxidation during storage.

During the programme, Mosley conveyed this message to viewers [C4]: ‘Some of the oils we’ve been told are good for us (most notably sunflower oil and vegetable oil), actually turned out to be potentially dangerous when used for cooking.’ He also emphasised that saturated fats like lard and butter, which are ‘usually demonised’, were least likely to produce high concentrations of toxins when fried at high temperatures, although they should be used ‘sparingly’. The findings broadcast in the documentary were widely covered in traditional and online media [C5]. This included articles authored by Mosley in the BBC’s online news magazine [C4] and the Daily Mail [C4]. As an indication of the impact of the media coverage on public understanding, the Mail article, which was shared 9,000 times on social media, received 1,130 comments from readers, of which nearly 70% responded positively [C5]. A large percentage (64%) confirmed that they would maintain their cooking practice by continuing with monosaturated and saturated frying oils [C4]. Another, albeit smaller group, said that they would modify their domestic frying/​cooking strategies to exclude polyunsaturated cooking oils as much as possible and replace them with monounsaturated oils (e.g. olive oil), a move that was in line with the article’s key message [C5]. The experiments performed for the documentary were cited in a ‘Fact Check’ article [C6] in The Conversation, which concluded that olive oil is one of the better options for frying foods.

Findings from the studies carried out for the BBC documentary, coupled with similar conclusions drawn in an article by Grootveld and colleagues in the American Oil Chemists’ Society magazine INFORM [C7], have had a sustained influence since June 2014. For example, The Telegraph covered the findings in two articles in November 2015, Women’s Health magazine (UK) published a related feature in 2016 and The Times ran similar articles in 2017, 2018 and 2019 [C5]. The Telegraph articles led to the New Zealand Heart Foundation reiterating this key message: ‘Avoid deep frying foods but if you must do so, avoid oils that are rich in polyunsaturated fats because these are unstable at high temperatures’ [C5]. The Australian Oilseeds Federation said Grootveld’s studies ‘vindicated the longstanding recommendations of the Australian oilseed industry that oils high in polyunsaturated fats, such as traditional sunflower and corn oil, should not be used for deep frying’ [C5].

Grootveld’s findings on thermal stressing of different fats during deep-frying informed a report compiled for the Healthier Catering Commitment (HCC) group. HCC is a London scheme and award, running across 22 boroughs in London and backed by the Greater London Authority, that supports fast-food businesses to make their food ‘healthier’. The Greenwich representative on the HCC, writing in 2018, said Grootveld’s input had been ‘very useful to our area of work’ and confirmed that some of the HCC criteria took into account frying method and the fat/oil used to fry foods [C8]. The Head of Nutrition for Jamie Oliver Group consulted Grootveld in 2017 ‘to make sure that the public health message that comes across [in Jamie Oliver’s books and TV shows] ties in with research such as yours [Grootveld’s] and that we aren’t recommending anything wildly inaccurate’. She said that as a result of Grootveld’s findings she would be asking the food development team ‘to check the temperature of the frying oil and the frying time for the recipes where this is relevant’ [C8]. Grootveld was acknowledged in the popular 2016 cook book River Cottage A to Z: Our Favourite Ingredients, and How to Cook Them for his research-based advice on cooking fats and oils. Co-author Hugh Fearnley-Whittingstall [C8] wrote: ‘His [Grootveld’s] research and guidance have been crucial in allowing us to navigate this complex and confusing subject and present the most up-to-date information, in layperson’s terms, to readers.’ Noting that Grootveld’s work continues to inform his recipe writing, including ‘invaluable input’ for his upcoming book Eat Better Forever, due to be published December 2020, Fearnley-Whittingstall said the research ‘has been very instrumental in increasing my own knowledge in this area, and by extension the knowledge of my readers’.

The BTG have translated bench-top research into the development of novel DNA barcoding methods for the authentication of herbal medicines into safer, more efficient industrial quality control protocols and new global standards. Having recognised that DNA testing of medicinal plants could reduce dangerous contamination, benefit consumers and increase product quality and therefore confidence in the industry, they worked with the industry leader to establish commercially viable quality assurance methods. Concurrently they worked with global regulators to implement new standards and legislative changes that required the wider herbal medicines industry to change its approach and strengthen quality control procedures.

(1) INDUSTRY UPTAKE OF DNA-BASED QUALITY ASSURANCE METHODS

Schwabe Pharmaceuticals, part of the Dr Wilmar Schwabe Group, is the world-leading manufacturer of traditional herbal medicines (annual turnover: EUR900,000,000). Schwabe recognised that DNA-based tests offered an opportunity to further consolidate their market-leading position and respond to EU requirements for DNA-based testing to obtain market approval for herbal medicine products [C1]. The BTG secured EU FP7 funding to partner with Schwabe [G1] and led the development of DNA-based tests to authenticate some of Schwabe’s key commercial medicinal plants. By February 2016, BTG and Schwabe had sufficient evidence to conclude that the preferred method was the optimised, highly sensitive quantitative PCR developed at DMU. This technical approach required a high initial industrial infrastructure outlay, but Schwabe felt this was offset by the technology’s sensitivity, speed and capability of assessing the purity of the sample, as well as the fact that BTG methods could be developed to the company’s own specification [C1].

BTG researchers developed DNA-based tests to identify Rhodiola rosea, used in herbal medicine to reduce fatigue and stress, and differentiate it from other Rhodiola species. This addressed a significant challenge that Schwabe had been trying to resolve with a problematic supply chain issue. The company had identified an unacceptable variation in Rhodiola rosea found in the raw materials supplied to European buyers and this had resulted in significant variations in constituents present in its Rhodiola products [C2]. Schwabe therefore required a scientific method to standardise purchasing, particularly because Rhodiola rosea herb is the active ingredient of Vitano®, one of its best-selling products. In their study of R. rosea, the BTG team obtained DNA sequences for four DNA barcode regions and 10 potential contaminant species. They identified the most appropriate region from the DNA sequences on which to base the design of PCR primers, allowing them to distinguish between medicinal plants and the contaminant or non-target plants. Schwabe were able to adopt the quality control protocol developed by BTG for the authentication of R. rosea [C3].

In another project, BTG developed a DNA-based method to differentiate between two closely related Pelargonium species [C4]. Marketed by Schwabe under its Kaloba range, this medicinal product is used to relieve the symptoms of upper respiratory tract infections (pelargonium is listed under self-care treatments for acute coughs in NICE Guideline 120). The new method enabled Schwabe to protect their claim to the most potent species, protecting their competitive advantage and allowing them to meet EU pharmaceutical approval procedures [C1].

The Rhodiola assay was later published as a case study in the 2017 Planta Medica paper co-authored with the Schwabe team [R6], exemplifying a universal DNA barcoding authentication strategy for use across the industry. Schwabe notes: ‘As a company with the most expertise in phytochemical and pharmacological studies, we weren’t experts in developing or using DNA-based test systems to discriminate medicinal plant at DNA level. Therefore, for our company this collaboration project with the BTG at DMU was a very excellent and profitable experience’ [C1:pp.2]. The BTG helped to embed this new technology into company processes by training two research scientists and three technical staff, who were seconded by Schwabe to DMU. The company concludes that this ‘has given Schwabe as a company a decisive advantage in preparing or adjusting to the ever-increasing quality requirements and analytical methods that are increasingly required by the authorities like the German Federal Institute for Drugs and Medical Devices (BfArM) during approval procedures and that are slowly being introduced as a quality standard in e.g. the British and Chinese Pharmacopoeias’ [C1:pp.2].

(2) REGULATORY UPTAKE OF DNA-BASED STANDARDS TO INCREASE PRODUCT QUALITY AND REDUCE DANGEROUS CONTAMINATION

Slater and Howard recognised that DNA testing for medicinal plants would only be taken up across the herbal medicines industry if regulations stipulated it. Herbal medicines in the UK are regulated by the Medicines and Healthcare Products Regulatory Agency (MHRA), and the standards applied to specific products are written into ‘monographs’ within the British Pharmacopoeia (BP). Following discussions between BTG and the MHRA, Howard was appointed, in January 2014, to a new post within the BP in order to develop and embed an in-house DNA testing capability. This led to the founding of the BP Herbals Laboratory at the National Institute for Biological Standards and Controls (NIBSC) as an MHRA centre; with several new posts created to service the facility [C5, minutes 8^th June 2016:pp1]. The BP Laboratory has been shaped by BTG research. Howard was closely involved in crystallising the core concepts of DNA testing and transferred these to the new laboratory, while Slater was recruited to the BP Commission Panel of Experts DNA Identification Techniques Steering Committee, and subsequently appointed Chairman of the Expert DNA Panel [C5, minutes 8^th June 2016: pp2].

In 2015 BP published the world’s first pharmacopoeia barcode [C6]. This was for Holy Basil, and the decision was underpinned by DMU’s research on this genus [R4]. This gave the global industry access to a validated, DNA-based method to unambiguously identify plant material for the first time. To provide a ‘positive control’ for this method, a novel reference material was brought to market, with the BTG performing the fundamental Second Laboratory validation of the material and protocol [C7]. Over the impact period, the barcode sequences of eight key medicinal plants were published in the BP, each individually endorsed by the Expert Panel for DNA. The use of this technology increased the stringency of all benchmarks in the BP for herbal drugs by verifying the material used in their production. Identifying adulterated and mixed samples within the reference samples gave insight into how these materials appear in all analyses, allowing standards to be set that would rule them out.

The Chairman of the British Herbal Medicines Association provides an overview of the significance of these changes to industry standards:

The issues of adulteration and contamination are complex and may be caused intentionally or through misidentification. Recent research carried out by the BHMA suggests that this may affect up to 40% of material available on the UK marketplace. This issue is harmful to the industry as it can reduce the potency of the medicines administered, could cause ill health and reduce consumer confidence. For these reasons there is an urgent need for novel and accessible quality control measures, such as those published by the Biomolecular Technology Group of De Montfort University. The impact of these publications, and guest speaker appearances by several [BTG] members at BHMA seminars, has been to enable our members to understand the potential of these methods to answer their supply chain questions [C8].

The BP has a wide international reach as it is used as a reference standard in more than 100 countries [C9] and forms an inherent part of established medicines legislation in Commonwealth countries. For example, Australia and Canada have adopted the BP as their national standard, and therefore its DNA testing requirements. Through informing the BP, the research presented in this case study has influenced how the quality of herbal products should be assessed and enhanced in many countries around the world.

DMU research has had a direct impact on approaches to DNA barcoding in the United States. The US Pharmacopoeia (USP) is in the process of developing its own DNA tests. They invited Howard to be a keynote speaker at their 2018 workshop on DNA authentication and their strategy for developing DNA tests is based on the 2009 DMU paper [R1, C10]. USP state that DMU’s 2017; pp.1 paper [R6] in particular has had ‘a major influence’ on their work, noting that ‘these comprehensive guidelines are very important for researchers and industry’ [C10: pp.1]. They write: ‘Publications from the group informed and influenced the direction of our work regarding the suitable methods and the validation requirements for compendial standards’. This included, in 2018, the use of the methods described in R1 to investigate species–species identification of the American ginseng, Asian ginseng and Tienchi ginseng [C10]. The USP says this could ‘contribute to the introduction, for the first time, of the genomic methods for botanical identification to complement the current compendial identification methods’ [C10: pp.1].

DMU research [R6] has also informed USP policy towards developing new stricter quality standards that will be mandatory for herbal medicine manufacturers. It writes:

We are also referring to the group’s guidance regarding quality control decision points to update the USP General Chapter <563> Identification of the Articles of Botanical Origin to incorporate guidance regarding out-of-specification investigations. If specifications of a botanical monograph cite the analytical methods and acceptance criteria in a General Chapter, the requirements become mandatory for manufacturers who claim compliance with the monograph [C10: pp.1].

Ethnographic research co-led by Northcott has provided a detailed picture of the experiences of care for people living with dementia during an acute hospital admission, and a set of recommendations for how care can be improved for this vulnerable patient group. Through targeted media engagement, the study findings have stimulated high-profile public debate in the UK, influencing parliamentary deliberations and contributing to policy responses designed to optimise care for older people. The research has shaped new online and face-to-face dementia care training and informed a dementia-specific film programme to support social inclusion.

(1) Influencing public debates and policy responses to improve health outcomes for people living with dementia

In April 2018, Northcott and Featherstone shared their findings exclusively with The Observer and BBC Five Live to maximise their impact. The Observer article [C1] was viewed 48,718 times online and reached up to 160,000 people in print. It highlighted the key research conclusions: the organisation of wards is unsuitable for both people with dementia and staff, many of whom lack the required skills and training, and the use of containment techniques is frequently the trigger of resistance or cause of patient anxiety. The story was directly shared on social media 232 times and generated 348 comments, featuring the perspectives of carers and health professionals. The article prompted a formal statement from the Department of Health and Social Care (DHSC) [C1] and quoted the president of the British Geriatrics Society: ‘These findings are a huge concern. Sometimes the use of containment techniques is not justified’ [C1].

The study formed the basis of a 45-minute radio piece on BBC Five Live Investigates titled ‘Dementia Care’ [C2a], in which the research was featured for the entirety of the programme. Its audience reach was up to 5,000,000; it featured interviews with a carer, a person living with dementia, a nurse and a representative from Dementia UK. It prompted another statement from DHSC and a statement from the Royal College of Nursing, who cited the research as evidence for the need to increase hospital staffing levels, saying that unsafe staffing levels were contributing to a culture of dehumanisation [C2a]. The Five Live team made an accompanying two-minute film for the BBC News website about the research. It was the most viewed news item on the BBC News website for the relevant 24-hour period [C2b].

The Five Live piece led to an invitation from care charity The Edith Ellen Foundation to discuss the findings at a panel event on dementia and healthcare at the House of Lords in June 2018 [C3]. This led to an invitation to present the evidence at the All-Party Parliamentary Group on Dementia inquiry on Dementia and Disability in November 2018 [C3]. The research was cited directly by the Royal College of Nursing (RCN) in its formal recommendations on education and training in a NICE review of quality standards and indicators in dementia care in November 2018 [C4, p112].

In Wales, the media coverage of the research in April 2018 resulted in it being cited in the Senedd the following month, in a question put by Welsh Assembly Member Lynne Neagle to the Cabinet Secretary for Health and Social Services. She cited the studies to support her call for the provision of ‘person-centred care to people with dementia’; the Cabinet Secretary said the Welsh Government would address this [C5 paragraph 168]. The findings were presented and discussed at a meeting of the Welsh Assembly Cross-Party Group on Dementia in October 2018, at the invitation of Neagle (Group chair) [C6]. This led to the launch of the Group’s inquiry into hospital care, which was due to report in spring 2020 until delayed by the Covid-19 pandemic [C6].

As part of the rollout of the 2018-2022 Dementia Action Plan for Wales, the Welsh Government and Public Health Cymru related the study findings to Improvement Cymru (improvement service for NHS Wales). From November 2019 Improvement Cymru presented the research to health boards in Wales to guide best practice and improve recognition of dementia within acute hospital wards [C8]. The BBC and Observer coverage also led directly to a request for research data by the team authoring the All Wales Safeguarding Procedures (measures protecting vulnerable adults), which were published in April 2020. This data contributed to the sections that provided guidance on professional abuse and protecting the well-being of patients.

(2) Changing clinical practice through specialist online and face-to-face staff training

As a direct result of the research, Public Health Wales and NHS Cymru invited Northcott and Featherstone, in 2019, to design and deliver a training programme for the leaders of all seven NHS Health Boards in Wales. This was accompanied by training for nursing and ward staff from three NHS Trusts in collaboration with Dementia UK [C8]. The aim of the programme was to raise awareness of the needs of people living with dementia at an organisational level, and to provide the tools for these organisations to develop their own low- or no-cost strategies to improve care. Initial training took place at Cardiff and the Vale University Health Board in November 2019. Nine further sessions were scheduled to take place from March 2020 onwards were postponed due to Covid-19. The research also featured as an ‘NIHR Signal’ in the BMJ in 2019 – Signal briefings are aimed at healthcare decision makers [C7a, b].

Northcott and Featherstone produced training films based on the research, in collaboration with professional film-makers, Dementia UK and Open University. They included testimonials from research participants, carers, nurses and people living with dementia themselves. Shortened versions (under a minute each) were also produced for dissemination via Facebook and Twitter during annual events like Dementia Awareness Week [C3]. These films, together with the project website www.storiesofdementia.com and the media engagement, were recognised by the NIHR as best practice for engaging non-academic audiences in health research [C3]. Parts of these films have been used (and continue to be used) by acute hospitals within Aneurin Bevan University Health Board as part of their ongoing CPD provision for nursing and ward staff [C8]. The Board’s R&D Director wrote that the research has ‘supported nursing leadership around dementia care within our acute hospital care settings [which serve a population of 600,000] and promoted the research culture and capacity within our organisation’ [C8].

The same resources were used for training days organised by Dementia UK and attended by its Admiral Nurses. Beginning in October 2017, these sessions enabled Admiral Nurses to design ‘hacks’ or mini-interventions to implement practice improvements in hospital and community settings [C9]. Dementia UK wrote that the research was ‘particularly influential in helping us to refine the Admiral Nurse “offer” in supporting the acute sector to deliver person-centred care … the numbers of acute care partnerships we have are increasing exponentially as a result’ [C9]. The NIHR funded the development (with the Open University) of a CPD-approved FutureLearn online course: Dementia care in hospital: Caring for people living with dementia in acute hospital wards, the launch of which has been postponed to 2021 due to Covid-19.

(3) Enabling social inclusion through the design of dementia-friendly film screenings and a new play on the experiences of under-represented communities

The studies highlighted the invisibility and precariousness typically experienced by people living with dementia. Northcott and Featherstone created the ‘Tinted Lens’ film initiative, as part of the public engagement strand of the research programme, to support the integration of an often-excluded audience. Working alongside charities and arts organisations (including Carers UK, Dementia UK, British Film Institute (BFI), Film Hub Wales (FHW) and Chapter Arts), they co-designed the toolkit: Dementia Friendly Screenings: A Guide for Cinemas. They co-organised film screenings during Dementia Awareness Week in 2017 and 2018, in collaboration with Chapter Arts and funded by the BFI and FHW. They were attended by 600 people living with dementia and their families. The 2017 event led to monthly dementia-friendly screenings that were attended by 20–100 members of the public and covered by The Guardian [C10a] and the BBC [C10b]; cinema-goers had an opportunity to chat with each other and staff and the auditorium was adapted to be as calming and comfortable as possible. FHW reports that the Tinted Lens initiative helped them ‘gain momentum and crucial awareness’ and demonstrate that the model worked and could be replicated on a wider scale. Its Strategic Hub Manager wrote: ‘Dementia friendly cinema is now a staple in many cinema calendars, with cinemas confident in offering this to their customers as part of their core programmes’ [C11].

A play exploring the experiences of dementia care among vulnerable or under-represented communities (e.g. the D/deaf community, BAME groups) drew directly on the ethnographic approach of Northcott and Featherstone’s studies [C12]. Next of Kin was written by Cardiff University Research Fellow Sofia Vougioukalou and directed by Julia Thomas from National Theatre Wales. The play was shown online in December 2020, as part of the 2020 Festival of Social Science, by Y Lab, a Cardiff University and Nesta collaboration. Produced in partnership with Alzheimer’s Society Cymru and Reality Theatre, an accompanying webinar ‘shared insights from a diverse group of people with the aim of creating shared learning, an impactful understanding of diversity in adult dementia care and a more equal care system’ [C12].