Map of the Handbook of Meta-Research

This chapter introduces each contribution contained within the Handbook of Meta-Research. The chapters in the handbook are organised into four sections which represent many of the key focus areas of past and current meta-research. These four sections include: Public value of research; Policy and governance of research; Knowledge dynamics; and Research cultures and careers. The chapter ends by stating the main objective of this Handbook, which is to facilitate discussions within the meta-research space towards a more inclusive and interdisciplinary production of knowledge that we can use to simultaneously produce valuable, high-quality research as well as enrich the understanding of the environment in which we work

Meta-research as discipline, field, or spectrum

This chapter examines the current state of meta-research. Specifically, we explore meta-research’s dynamic nature as a unique characteristic of an area of study that requires researchers to examine the practices, processes and norms within which their own work is situated. In addition, the interdisciplinary nature of meta-research presents epistemological tensions around notions of research quality, that also are an important area of study and of constant examination and debate for meta-researchers. This chapter examines the potential consequences of this diversity on the recognition of meta-research as a field or discipline. The chapter concludes with an acknowledgement that the field benefits from keeping disciplinary borders fluid as a way of encouraging and valuing interdisciplinary perspectives and experiences of meta research

Towards characterising negative impact:Introducing Grimpact

This paper categorises the nature of what we have labelled as the potential for ‘GrImpact’, in the evaluation of the wider influence of research, beyond academia. As the impact agenda broadly defined grows to include more formally criteria that consider the value of research beyond academia, so too does the pressure to ensure that these assessments of public value are conducted with the public’s best interests in mind. In many cases, any negative impact from research cannot be foreseen at the time of the evaluation, making it vital that any kinds of rewards for impact stimulate only positive public benefits (aka “the right type” of impact). Using a series of case studies of identified “negative impact” this paper explores the concept of Grimpact, as well as creates typologies of its characteristics and precursors

Reaching “an audience that you would never dream of speaking to”: influential public health researchers’ views on the role of news media in influencing policy and public understanding.

While governments and academic institutions urge researchers to engage with news media, traditional academic values of public disengagement have inhibited many from giving high priority to media activity. In this interview-based study, we report on the views about news media engagement and strategies used by 36 peer-voted leading Australian public health researchers in six fields. We consider their views about the role and importance of media in influencing policy; their reflections on effective or ineffective media communicators; and strategies used by these researchers about how to best retain their credibility and influence while engaging with the news media. A willingness and capacity to engage with the mass media was seen as an essential attribute of influential public health researchers.NHMR

Reaching “an audience that you would never dream of speaking to”: influential public health researchers’ views on the role of news media in influencing policy and public understanding.

While governments and academic institutions urge researchers to engage with news media, traditional academic values of public disengagement have inhibited many from giving high priority to media activity. In this interview-based study, we report on the views about news media engagement and strategies used by 36 peer-voted leading Australian public health researchers in six fields. We consider their views about the role and importance of media in influencing policy; their reflections on effective or ineffective media communicators; and strategies used by these researchers about how to best retain their credibility and influence while engaging with the news media. A willingness and capacity to engage with the mass media was seen as an essential attribute of influential public health researchers.NHMR

Challenges in assessing the characteristics of influential public health research.

The development of frameworks to effectively measure both the scientific and social impact of research is a topic of international debate. This paper examines how Australian public health researchers in six fields (alcohol, drugs, injury, obesity, skin cancer and tobacco) classified the scientific and social impact of what they judged to be their five most influential papers. We compared classifications of researchers rated as most influential by their peers with those not as highly ranked. Highly ranked researchers more often indicated social impact characteristics (Χ2 = 8.13; P = 0.004) than their less influential colleagues. Traditional measures of scientific impact (publication in high impact journals and high citations) were nominated by all researchers regardless of peer-nominated research influence status. There was strong consensus on who were the most influential researchers in five of the six research fields examined. This would appear to provide a sound platform on which to base more qualitative, interview or portfolio-based investigations into the complexities of wider conceptions of research and researcher influence

Identifying Trustworthy Experts: How Do Policymakers Find and Assess Public Health Researchers Worth Consulting or Collaborating With?

This paper reports data from semi-structured interviews on how 26 Australian civil servants, ministers and ministerial advisors find and evaluate researchers with whom they wish to consult or collaborate. Policymakers valued researchers who had credibility across the three attributes seen as contributing to trustworthiness: competence (an exemplary academic reputation complemented by pragmatism, understanding of government processes, and effective collaboration and communication skills); integrity (independence, “authenticity”, and faithful reporting of research); and benevolence (commitment to the policy reform agenda). The emphases given to these assessment criteria appeared to be shaped in part by policymakers' roles and the type and phase of policy development in which they were engaged. Policymakers are encouraged to reassess their methods for engaging researchers and to maximise information flow and support in these relationships. Researchers who wish to influence policy are advised to develop relationships across the policy community, but also to engage in other complementary strategies for promoting research-informed policy, including the strategic use of mass media

Antidepressant treatment with sertraline for adults with depressive symptoms in primary care : the PANDA research programme including RCT

Background Despite a growing number of prescriptions for antidepressants (over 70 million in 2018), there is uncertainty about when people with depression might benefit from antidepressant medication and concern that antidepressants are prescribed unnecessarily. Objectives The main objective of the PANDA (What are the indications for Prescribing ANtiDepressAnts that will lead to a clinical benefit?) research programme was to provide more guidance about when antidepressants are likely to benefit people with depression. We aimed to estimate the minimal clinically important difference for commonly used self-administered scales for depression and anxiety, and to understand more about how patients respond to such assessments. We carried out an observational study of patients with depressive symptoms and a placebo-controlled randomised controlled trial of sertraline versus placebo to estimate the treatment effect in UK primary care. The hypothesis was that the severity and duration of symptoms were related to treatment response. Design The programme consisted of three phases. The first phase relied on the secondary analysis of existing data extracted from published trials. The second phase was the PANDA cohort study of patients with depressive symptoms who presented to primary care and were followed up 2, 4 and 6 weeks after a baseline assessment. Both quantitative and qualitative methods were used in the analysis. The third phase was a multicentre randomised placebo-controlled double-blind trial of sertraline versus placebo in patients presenting to primary care with depressive symptoms. Setting UK primary care in Bristol, London, Liverpool and York. Participants Patients aged 18–74 years who were experiencing depressive symptoms in primary care. Eligibility for the PANDA randomised controlled trial included that there was uncertainty about the benefits about treatment with an antidepressant. Interventions In the PANDA randomised controlled trial, patients were individually randomised to 100 mg daily of sertraline or an identical placebo. The PANDA cohort study was an observational study. Main outcome measures Depressive symptoms measured using the Patient Health Questionnaire were the primary outcome for the randomised controlled trial. Other outcomes included anxiety symptoms using the Generalised Anxiety Disorder-7; depressive symptoms using the Beck Depression Inventory, version 2; health-related quality of life; self-reported improvement; and cost-effectiveness. Results The secondary analysis of existing randomised controlled trials [GENetic and clinical Predictors Of treatment response in Depression (GenPod), TREAting Depression with physical activity (TREAD) and Clinical effectiveness and cost-effectiveness of cognitive Behavioural Therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care (CoBalT)] found evidence that the minimal clinically important difference increased as the initial severity of depressive symptoms rose. Our estimates of minimal clinically important difference were a 17% and 18% reduction in Beck Depression Inventory scores for GenPod and TREAD, respectively. In CoBalT, a 32% reduction corresponded to the minimal clinically important difference but the participants in this study had depression that had not responded to antidepressants. In the PANDA study cohort, and from our analyses in existing data, we found that the minimal clinically important difference varies considerably with the initial severity of depressive and anxiety symptoms. Expressing the minimal clinically important difference as a percentage reduction reduces this variation at higher scores, but at low scores the percentage reduction increased substantially. The results from the qualitative studies pointed out many limitations of the Patient Health Questionnaire-9 items in assessing change and recovery from depression. In the PANDA randomised controlled trial, there was no evidence that sertraline resulted in a reduction in depressive symptoms within 6 weeks of randomisation, but there was some evidence of a reduction by 12 weeks. However, sertraline led to a reduction in anxiety symptoms, an improvement of mental health-related quality of life and an increased likelihood of reporting improvement. The mean Patient Health Questionnaire-9 items score at 6 weeks was 7.98 (standard deviation 5.63) in the sertraline group and 8.76 (standard deviation 5.86) in the placebo group (5% relative reduction, 95% confidence interval –7% to 15%; p = 0.41). Of the secondary outcomes, there was strong evidence that sertraline reduced anxiety symptoms (Generalised Anxiety Disorder-7 score reduced by 17% (95% confidence interval 9% to 25%; p = 0.00005). Sertraline had a high probability (> 90%) of being cost-effective at 12 weeks. The PANDA randomised controlled trial found no evidence that treatment response or cost-effectiveness was related to severity or duration of depressive symptoms. The minimal clinically important difference estimates suggested that sertraline’s effect on anxiety, but not on depression, was likely to be clinically important. Limitations The results from the randomised controlled trial and the estimates of minimal clinically important difference were not sufficiently precise to provide specific clinical guidance for individuals. We had low power in testing whether or not initial severity and duration of depressive symptoms are related to treatment response. Conclusions The results of the trial support the use of sertraline and probably other selective serotonin reuptake inhibitors because of their action in reducing anxiety symptoms and the likelihood of longer-term benefit on depressive symptoms. Sertraline could be prescribed for anxiety symptoms that commonly occur with depression and many patients will experience a clinical benefit. The Patient Health Questionnaire-9 items and similar self-administered scales should not be used on their own to assess clinical outcome, but should be supplemented with further clinical assessment. Future work We need to examine the longer-term effects of antidepressant treatment. We need more precise estimates of the treatment effects and minimal clinically important difference at different severities to provide more specific guidance for individuals. However, the methods we have developed provide an approach towards providing such detailed guidance. Trial registration Current Controlled Trials ISRCTN84544741 and EudraCT number 2013-003440-22. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 10. See the NIHR Journals Library website for further project information

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains

Background: Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Methods: Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. Results: 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). Conclusions: In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread