Public preferences for delayed or immediate antibiotic prescriptions in UK primary care: A choice experiment.

BACKGROUND: Delayed (or "backup") antibiotic prescription, where the patient is given a prescription but advised to delay initiating antibiotics, has been shown to be effective in reducing antibiotic use in primary care. However, this strategy is not widely used in the United Kingdom. This study aimed to identify factors influencing preferences among the UK public for delayed prescription, and understand their relative importance, to help increase appropriate use of this prescribing option. METHODS AND FINDINGS: We conducted an online choice experiment in 2 UK general population samples: adults and parents of children under 18 years. Respondents were presented with 12 scenarios in which they, or their child, might need antibiotics for a respiratory tract infection (RTI) and asked to choose either an immediate or a delayed prescription. Scenarios were described by 7 attributes. Data were collected between November 2018 and February 2019. Respondent preferences were modelled using mixed-effects logistic regression. The survey was completed by 802 adults and 801 parents (75% of those who opened the survey). The samples reflected the UK population in age, sex, ethnicity, and country of residence. The most important determinant of respondent choice was symptom severity, especially for cough-related symptoms. In the adult sample, the probability of choosing delayed prescription was 0.53 (95% confidence interval (CI) 0.50 to 0.56, p < 0.001) for a chesty cough and runny nose compared to 0.30 (0.28 to 0.33, p < 0.001) for a chesty cough with fever, 0.47 (0.44 to 0.50, p < 0.001) for sore throat with swollen glands, and 0.37 (0.34 to 0.39, p < 0.001) for sore throat, swollen glands, and fever. Respondents were less likely to choose delayed prescription with increasing duration of illness (odds ratio (OR) 0.94 (0.92 to 0.96, p < 0.001)). Probabilities of choosing delayed prescription were similar for parents considering treatment for a child (44% of choices versus 42% for adults, p = 0.04). However, parents differed from the adult sample in showing a more marked reduction in choice of the delayed prescription with increasing duration of illness (OR 0.83 (0.80 to 0.87) versus 0.94 (0.92 to 0.96) for adults, p for heterogeneity p < 0.001) and a smaller effect of disruption of usual activities (OR 0.96 (0.95 to 0.97) versus 0.93 (0.92 to 0.94) for adults, p for heterogeneity p < 0.001). Females were more likely to choose a delayed prescription than males for minor symptoms, particularly minor cough (probability 0.62 (0.58 to 0.66, p < 0.001) for females and 0.45 (0.41 to 0.48, p < 0.001) for males). Older people, those with a good understanding of antibiotics, and those who had not used antibiotics recently showed similar patterns of preferences. Study limitations include its hypothetical nature, which may not reflect real-life behaviour; the absence of a "no prescription" option; and the possibility that study respondents may not represent the views of population groups who are typically underrepresented in online surveys. CONCLUSIONS: This study found that delayed prescription appears to be an acceptable approach to reducing antibiotic consumption. Certain groups appear to be more amenable to delayed prescription, suggesting particular opportunities for increased use of this strategy. Prescribing choices for sore throat may need additional explanation to ensure patient acceptance, and parents in particular may benefit from reassurance about the usual duration of these illnesses.

Why do hospital prescribers continue antibiotics when it is safe to stop? Results of a choice experiment survey.

BACKGROUND: Deciding whether to discontinue antibiotics at early review is a cornerstone of hospital antimicrobial stewardship practice worldwide. In England, this approach is described in government guidance ('Start Smart then Focus'). However, < 10% of hospital antibiotic prescriptions are discontinued at review, despite evidence that 20-30% could be discontinued safely. We aimed to quantify the relative importance of factors influencing prescriber decision-making at review. METHODS: We conducted an online choice experiment, a survey method to elicit preferences. Acute/general hospital prescribers in England were asked if they would continue or discontinue antibiotic treatment in 15 hypothetical scenarios. Scenarios were described according to six attributes, including patients' presenting symptoms and whether discontinuation would conflict with local prescribing guidelines. Respondents' choices were analysed using conditional logistic regression. RESULTS: One hundred respondents completed the survey. Respondents were more likely to continue antibiotics when discontinuation would 'strongly conflict' with local guidelines (average marginal effect (AME) on the probability of continuing + 0.194 (p < 0.001)), when presenting symptoms more clearly indicated antibiotics (AME of urinary tract infection symptoms + 0.173 (p < 0.001) versus unclear symptoms) and when patients had severe frailty/comorbidities (AME = + 0.101 (p < 0.001)). Respondents were less likely to continue antibiotics when under no external pressure to continue (AME = - 0.101 (p < 0.001)). Decisions were also influenced by the risks to patient health of continuing/discontinuing antibiotic treatment. CONCLUSIONS: Guidelines that conflict with antibiotic discontinuation (e.g. pre-specify fixed durations) may discourage safe discontinuation at review. In contrast, guidelines conditional on patient factors/treatment response could help hospital prescribers discontinue antibiotics if diagnostic information suggesting they are no longer needed is available.

Correction to: Will the reformed Cancer Drugs Fund address the most common types of uncertainty? An analysis of NICE cancer drug appraisals.

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Will the reformed Cancer Drugs Fund address the most common types of uncertainty? An analysis of NICE cancer drug appraisals.

BACKGROUND: One of the functions of the reformed Cancer Drugs Fund in England is as a managed access fund, providing conditional funding for cancer drugs where there is uncertainty in the economic case, and where that uncertainty can be addressed by data collection during two years' use in the NHS. Our study characterises likely sources of such uncertainty, through a review of recent NICE Technology Appraisals. METHODS: Discussions of uncertainty in NICE Appraisal Committees were extracted from published Single Technology Appraisals of cancer drugs, 2014-2016, and categorised inductively. The location of the comments within the structured Appraisal document was used as a proxy for the degree of concern shown by the Committee. RESULTS: Twenty-nine appraisals were analysed, of which 23 (79%) were recommended for funding. Six main sources of uncertainty were identified. Immaturity of survival data, and issues relating to comparators, were common sources of uncertainty regardless of degree of concern. Uncertainties relating to quality of life, and the patient population in the trial, were discussed frequently but rarely occurred in the more uncertain appraisals. Concerns with trial design, and cost uncertainty, were less common, but a high proportion contributed to the most uncertain appraisals. Funding decisions were not driven by uncertainty in the evidence base, but by the expected cost per QALY relative to acceptance thresholds, and the resultant level of uncertainty in the decision. CONCLUSIONS: The reformed CDF is an improvement on its predecessor. However the main types of uncertainty seen in recent cancer appraisals will not readily be resolved solely by 2 years' RWD collection in the reformed CDF; where there are no ongoing trials to provide longer-term data, randomised trials rather than RWD may be needed to fully resolve questions of relative efficacy. Other types of uncertainty, and concerns with generalisability, may be more amenable to the RWD approach, and it is these that we expect to be the focus of data collection arrangements in the reformed CDF.

Cancer drug funding decisions in Scotland: impact of new end-of-life, orphan and ultra-orphan processes.

BACKGROUND: The Scottish Medicines Consortium evaluates new drugs for use in the National Health Service in Scotland. Reforms in 2014 to their evaluation process aimed to increase patient access to new drugs for end-of-life or rare conditions; the changes include additional steps in the process to gain further information from patients and clinicians, and for revised commercial agreements. This study examines the extent of any impact of the reforms on funding decisions. METHOD: Data on the Scottish Medicines Consortium's funding decisions during 24 months post-reform were extracted from published Advice, for descriptive statistics and thematic analysis. Comparison data were extracted for the 24 months pre-reform. Data on decisions for England by the National Institute for Clinical and Health Excellence for the same drugs were extracted from published Technology Appraisals. RESULTS: The new process was used by 90% (53/59) of cancer submissions. It is triggered if the initial advice is not to recommend, and this risk-of-rejection level is higher than in the pre-period. Thirty-eight cancer drugs obtained some level of funding through the new process, but there was no significant difference in the distribution of decision types compared to the pre-reform period. Thematic analysis of patient and clinician input showed no clear relationship between issues raised and funding decision. Differences between SMC's and NICE's definitions of End-of-Life did not fully explain differences in funding decisions. CONCLUSIONS: The Scottish Medicines Consortium's reforms have allowed funding of up to 38 cancer drugs that might previously have been rejected. However, the contribution of specific elements of the reforms to the final decision is unclear. The process could be improved by increased transparency in how the non-quantitative inputs influence decisions. Some disparities in funding decisions between England and Scotland are likely to remain despite recent process convergence.

Overcoming challenges in the economic evaluation of interventions to optimise antibiotic use.

Bacteria are becoming increasingly resistant to antibiotics, reducing our ability to treat infections and threatening to undermine modern health care. Optimising antibiotic use is a key element in tackling the problem. Traditional economic evaluation methods do not capture many of the benefits from improved antibiotic use and the potential impact on resistance. Not capturing these benefits is a major obstacle to optimising antibiotic use, as it fails to incentivise the development and use of interventions to optimise the use of antibiotics and preserve their effectiveness (stewardship interventions). Estimates of the benefits of improving antibiotic use involve considerable uncertainty as they depend on the evolution of resistance and associated health outcomes and costs. Here we discuss how economic evaluation methods might be adapted, in the face of such uncertainties. We propose a threshold-based approach that estimates the minimum resistance-related costs that would need to be averted by an intervention to make it cost-effective. If it is probable that without the intervention costs will exceed the threshold then the intervention should be deemed cost-effective.

Implementing antibiotic stewardship in high-prescribing English general practices: a mixed-methods study.

BACKGROUND: Trials have identified antimicrobial stewardship (AMS) strategies that effectively reduce antibiotic use in primary care. However, many are not commonly used in England. The authors co-developed an implementation intervention to improve use of three AMS strategies: enhanced communication strategies, delayed prescriptions, and point-of-care C-reactive protein tests (POC-CRPTs). AIM: To investigate the use of the intervention in high-prescribing practices and its effect on antibiotic prescribing. DESIGN AND SETTING: Nine high-prescribing practices had access to the intervention for 12 months from November 2019. This was primarily delivered remotely via a website with practices required to identify an 'antibiotic champion'. METHOD: Routinely collected prescribing data were compared between the intervention and the control practices. Intervention use was assessed through monitoring. Surveys and interviews were conducted with professionals to capture experiences of using the intervention. RESULTS: There was no evidence that the intervention affected prescribing. Engagement with intervention materials differed substantially between practices and depended on individual champions' preconceptions of strategies and the opportunity to conduct implementation tasks. Champions in five practices initiated changes to encourage use of at least one AMS strategy, mostly POC-CRPTs; one practice chose all three. POC-CRPTs was used more when allocated to one person. CONCLUSION: Clinicians need detailed information on exactly how to adopt AMS strategies. Remote, one-sided provision of AMS strategies is unlikely to change prescribing; initial clinician engagement and understanding needs to be monitored to avoid misunderstanding and suboptimal use.

We need to talk about values: a proposed framework for the articulation of normative reasoning in health technology assessment.

It is acknowledged that health technology assessment (HTA) is an inherently value-based activity that makes use of normative reasoning alongside empirical evidence. But the language used to conceptualise and articulate HTA's normative aspects is demonstrably unnuanced, imprecise, and inconsistently employed, undermining transparency and preventing proper scrutiny of the rationales on which decisions are based. This paper - developed through a cross-disciplinary collaboration of 24 researchers with expertise in healthcare priority-setting - seeks to address this problem by offering a clear definition of key terms and distinguishing between the types of normative commitment invoked during HTA, thus providing a novel conceptual framework for the articulation of reasoning. Through application to a hypothetical case, it is illustrated how this framework can operate as a practical tool through which HTA practitioners and policymakers can enhance the transparency and coherence of their decision-making, while enabling others to hold them more easily to account. The framework is offered as a starting point for further discussion amongst those with a desire to enhance the legitimacy and fairness of HTA by facilitating practical public reasoning, in which decisions are made on behalf of the public, in public view, through a chain of reasoning that withstands ethical scrutiny.

What Aspects of Illness Influence Public Preferences for Healthcare Priority Setting? A Discrete Choice Experiment in the UK.

BACKGROUND: Decisions on funding new healthcare technologies assume that all health improvements are valued equally. However, public reaction to health technology assessment (HTA) decisions suggests there are health attributes that matter deeply to them but are not currently accounted for in the assessment process. We aimed to determine the relative importance of attributes of illness that influence the value placed on alleviating that illness. METHOD: We conducted a discrete choice experiment survey that presented general public respondents with 15 funding decisions between hypothetical health conditions. The conditions were defined by five attributes that characterise serious illnesses, plus the health gain from treatment. Respondent preferences were modelled using conditional logistic regression and latent class analysis. RESULTS: 905 members of the UK public completed the survey in November 2017. Respondents generally preferred to provide treatments for conditions with 'better' characteristics. The exception was treatment availability, where respondents preferred to provide treatments for conditions where there is no current treatment, and were prepared to accept lower overall health gain to do so. A subgroup of respondents preferred to prioritise 'worse' health states. CONCLUSION: This study suggests a preference among the UK public for treating an unmet need; however, it does not suggest a preference for prioritising other distressing aspects of health conditions, such as limited life expectancy, or where patients are reliant on care. Our results are not consistent with the features currently prioritised in UK HTA processes, and the preference heterogeneity we identify presents a major challenge for developing broadly acceptable policy.

Impact of the COVID-19 Pandemic on Community Antibiotic Prescribing and Stewardship: A Qualitative Interview Study with General Practitioners in England.

The COVID-19 pandemic has had a profound impact on the delivery of primary care services. We aimed to identify general practitioners' (GPs') perceptions and experiences of how the COVID-19 pandemic influenced antibiotic prescribing and antimicrobial stewardship (AMS) in general practice in England. Twenty-four semi-structured interviews were conducted with 18 GPs at two time-points: autumn 2020 (14 interviews) and spring 2021 (10 interviews). Interviews were audio-recorded, transcribed and analysed thematically, taking a longitudinal approach. Participants reported a lower threshold for antibiotic prescribing (and fewer consultations) for respiratory infections and COVID-19 symptoms early in the pandemic, then returning to more usual (pre-pandemic) prescribing. They perceived the pandemic as having had less impact on antibiotic prescribing for urinary and skin infections. Participants perceived the changing ways of working and consulting (e.g., proportions of remote and in-person consultations) in addition to changing patient presentations and GP workloads as influencing the fluctuations in antibiotic prescribing. This was compounded by decreased engagement with, and priority of, AMS due to COVID-19-related urgent priorities. Re-engagement with AMS is needed, e.g., through reviving antibiotic prescribing feedback and targets/incentives. The pandemic disrupted, and required adaptations in, the usual ways of working and AMS. It is now important to identify opportunities, e.g., for re-organising ways of managing infections and AMS in the future.

Preferences for Medical Consultations from Online Providers: Evidence from a Discrete Choice Experiment in the United Kingdom.

BACKGROUND: In the UK, consultations for prescription medicines are available via private providers such as online pharmacies. However, these providers may have lower thresholds for prescribing certain drugs. This is a particular concern for antibiotics, given the increasing burden of antimicrobial resistance. Public preferences for consultations with online providers are unknown, hence the impact of increased availability of online consultations on antibiotic use and population health is unclear. OBJECTIVE: To conduct a discrete choice experiment survey to understand UK public preferences for seeking online consultations, and the factors that influence these preferences, in the context of having symptoms for which antibiotics may be appropriate. METHODS: In a survey conducted between July and August 2018, general population respondents completed 16 questions in which they chose a primary care consultation via either their local medical centre or an online provider. Consultations were described in terms of five attributes, including cost and similarity to traditional 'face-to-face' appointments. Choices were modelled using regression analysis. RESULTS: Respondents (n = 734) placed a high value on having a consultation via their local medical centre rather than an online provider, and a low value on consultations by phone or video. However, respondents characterised as 'busy young professionals' showed a lower strength of preference for traditional consultations, with a higher concern for convenience. CONCLUSION: Before COVID-19, the UK public had limited appetite for consultations with online providers, or for consultations that were not face-to-face. Nevertheless, prescriptions from online providers should be monitored going forward, particularly for antibiotics, and in key patient groups.

Delayed Antibiotic Prescription by General Practitioners in the UK: A Stated-Choice Study.

Delayed antibiotic prescription in primary care has been shown to reduce antibiotic consumption, without increasing risk of complications, yet is not widely used in the UK. We sought to quantify the relative importance of factors affecting the decision to give a delayed prescription, using a stated-choice survey among UK general practitioners. Respondents were asked whether they would provide a delayed or immediate prescription in fifteen hypothetical consultations, described by eight attributes. They were also asked if they would prefer not to prescribe antibiotics. The most important determinants of choice between immediate and delayed prescription were symptoms, duration of illness, and the presence of multiple comorbidities. Respondents were more likely to choose a delayed prescription if the patient preferred not to have antibiotics, but consultation length had little effect. When given the option, respondents chose not to prescribe antibiotics in 51% of cases, with delayed prescription chosen in 21%. Clinical features remained important. Patient preference did not affect the decision to give no antibiotics. We suggest that broader dissemination of the clinical evidence supporting use of delayed prescription for specific presentations may help increase appropriate use. Establishing patient preferences regarding antibiotics may help to overcome concerns about patient acceptance. Increasing consultation length appears unlikely to affect the use of delayed prescription.

Awareness of Appropriate Antibiotic Use in Primary Care for Influenza-Like Illness: Evidence of Improvement from UK Population-Based Surveys.

Influenza-like illnesses (ILI) account for a significant portion of inappropriate antibiotic use. Patient expectations for antibiotics for ILI are likely to play a substantial role in 'unnecessary' antibiotic consumption. This study aimed to investigate trends in awareness of appropriate antibiotic use and antimicrobial resistance (AMR). Three sequential online surveys of independent representative samples of adults in the United Kingdom investigated expectations for, and consumption of, antibiotics for ILI (May/June 2015 (n = 2064); Oct/Nov 2016 (n = 4000); Mar 2017 (n = 4000)). Respondents were asked whether they thought antibiotics were effective for ILI and about their antibiotic use. Proportions and 95% confidence intervals (CI) were calculated for each question and interactions with respondent characteristics were tested using logistic regression. Over the three surveys, the proportion of respondents who believed antibiotics would "definitely/probably" help an ILI fell from 37% (95% CI 35-39%) to 28% (95% CI 26-29%). Those who would "definitely/probably" visit a doctor in this situation fell from 48% (95% CI 46-50%) to 36% (95% CI 34-37%), while those who would request antibiotics during a consultation fell from 39% (95% CI 37-41%) to 30% (95% CI 29-32%). The percentage of respondents who found the information we provided about AMR "new/surprising" fell from 34% (95% CI 32-36%) to 28% (95% CI 26-31%). Awareness improved more among black, Asian and minority ethnic (BAME) than white people, with little other evidence of differences in improvements between subgroups. Whilst a degree of selection bias is unavoidable in online survey samples, the results suggest that awareness of AMR and appropriate antibiotic use has recently significantly improved in the United Kingdom, according to a wide range of indicators.

Mind the gap? The platform trial as a working environment.

BACKGROUND: Trials have become bigger and more complicated due to the complexity introduced by biomarker stratification, and the advent of multi-arm multi-stage trials, and umbrella and basket platform designs. The trials unit at University College London has been at the forefront of this work, with ground-breaking trials such as STAMPEDE and FOCUS4. The trial management and data management teams on these trials have summarised the operational challenges, to enable the broader clinical trials community to learn from their experiences. In a small-scale qualitative study, we examined the personal experience of individual researchers working on these trials. COMMENTARY: We found reports of high workloads, with potentially significant stress for individuals and with an impact on their career choices. We conclude that there was an initial underestimation of the work required and of the inherent, largely unanticipated, challenges. We discuss the importance of fully understanding these trials' resource requirements, both for those writing grant applications and critically, for those with responsibility for deciding on funding. The working environment was characterised by three features: complexity, scale and heightened expectations. These features are highly attractive for professional development and engender high levels of loyalty and commitment. We observed a trade-off between these intrinsic rewards and the continuous demands of overlapping tasks, balancing a mix of routine and high-profile work, and the changing nature of pivotal roles. Such demands present challenges for colleague relationships, by enhancing the potential for competition and by disrupting the natural opportunities to pause, review and celebrate team achievements. In addition, molecular stratification in effect brings the patient into the trial office, as a specific individual, despite anonymisation, who is owed test results and a treatment decision. We discuss these observations with a view to interconnecting the need for compassion for patients with caring for the researchers engaged in the research ecosystem who are aiming to produce much hoped-for advances in medical science. CONCLUSIONS: There is a need for increased awareness of the challenge these studies place on those throughout the team delivering the study. Such considerations must influence leaders and funders, both in their initial budget considerations and throughout delivery.

Cancer as the "perfect storm"? A qualitative study of public attitudes to health conditions.

AIMS: Our aim is to identify important attributes of major diseases that shape how they are perceived by the public. METHODS AND RESULTS: Four focus groups among members of the public were recruited, in March and October 2016, and used semistructured discussion to explore important attributes of cancer, heart disease, stroke, dementia, mental illness, and infectious disease. Common themes were identified by using inductive thematic analysis.Five themes were identified: fear, impact on family and friends, hope, detection, and prevention. Fear of cancer includes not only fear of death but also of aggressive treatments. Loss of dignity is feared in dementia, while infectious disease raises fear of uncontrollable "plague"; in contrast, people with mental illness may themselves be seen as a potential threat. The impact of cancer and its treatment on family and friends was described as intense and all-consuming, even for those not involved directly in caring; with dementia and stroke, the family impact is taking on care, including funding, over the long term with little expectation of improvement. Hope is a major theme in cancer and stroke recovery, linked with the need to take action, often expressed in aggressive language of "fighting," but seen as futile in dementia. Detection difficulties for "silent" cancers mean that real treatment opportunities are missed; cardiovascular and infection risk, however, are seen as easy to identify and act on, whereas mental illness and dementia are seen as poorly diagnosed and with limited treatment options. Prevention awareness is high for cardiovascular disease and infection, lower for cancer, and limited for dementia and mental health. CONCLUSION: Although themes overlap across diseases, the specific concerns are different and each condition has a unique profile. Quantifying the relative importance of these themes could allow their incorporation in decision-making, not only when they occur as a named disease but also in any relevant condition.

Does the Public Prefer Health Gain for Cancer Patients? A Systematic Review of Public Views on Cancer and its Characteristics.

BACKGROUND: Policies such as the Cancer Drugs Fund in England assumed a societal preference to fund cancer care relative to other conditions, even if that resulted in lower health gain for the population overall. OBJECTIVE: The aim of this study was to investigate the evidence for such a preference among the UK public. METHODS: The MEDLINE, PubMed and Econlit electronic databases were searched for studies relating to preferences for prioritising cancer treatment, as well as studies relating to preferences for the characteristics of cancer (severity of disease, end-of-life). The searches were run in November 2015 and updated in March 2017. Empirical preference studies, studies of public views, and studies in English were included. RESULTS: We identified 24 studies relating to cancer preferences. Two directly addressed health trade-offs in the UK-one showed a preference for health gain in cancer, while the other found no such preference but provided results consistent with population health maximisation. Other studies mostly showed support for cancer but did not require a direct health trade-off. Severity and end-of-life searches identified 12 and 6 papers, respectively, which were additional to existing reviews. There is consistent evidence that people give priority to severe illness, while results for end-of-life are mixed. CONCLUSION: We did not find consistent support for a preference for health gains to cancer patients in the context of health maximisation. The evidence base is small and the results are highly sensitive to study design. There remains a contradiction between these findings and the popular view of cancer, and further work is required to determine the features of cancer which contribute to that view.