Thomas Round

The opportunities and challenges of pragmatic point-of-care randomised trials using routinely collected electronic records: Evaluations of two exemplar trials

BACKGROUND Pragmatic trials compare the effects of different decisions in usual clinical practice. OBJECTIVES To develop and evaluate methods to implement simple pragmatic trials using routinely collected electronic health records (EHRs) and recruiting patients at the point of care; to identify the barriers and facilitators for general practitioners (GPs) and patients and the experiences of trial participants. DESIGN Two exemplar randomised trials (Retropro and eLung) with qualitative evaluations. SETTING Four hundred and fifty-nine English and Scottish general practices contributing EHRs to a research database, of which 17 participated in the trials. PARTICIPANTS Retropro aimed to recruit 300 patients with hypercholesterolaemia and high cardiovascular risk and eLung aimed to recruit 150 patients with a chronic obstructive pulmonary disease exacerbation. INTERVENTIONS Retropro randomised between simvastatin and atorvastatin and eLung between immediate antibiotics and deferred or non-use. eLung recruited during an unscheduled consultation using EHR flagging. MAIN OUTCOME MEASURE Successful trial completion with implementation of information technology (IT) system for flagging and data processing and documentation of operational and scientific experiences. DATA SOURCES EHR research database. RESULTS The governance approval process took over 3 years. A total of 58.8% of the practices (n = 270) expressed interest in participating. The number of interested practices dropped substantially with each stage of the governance process. In Retropro, 6.5% of the practices (n = 30) were eventually approved and 3.7% (n = 17) recruited patients; in eLung, these numbers were 6.8% (n = 31) and 1.3% (n = 6) respectively. Retropro successfully completed recruitment (301 patients) whereas eLung recruited 31 patients. Retropro recruited 20.6% of all statin starters in recruiting practices and 1.1% in the EHR database; the comparable numbers for eLung were 32.3% and 0.9% respectively. The IT system allowed for complex eligibility criteria with central on and off control of recruitment and flagging at a practice. Good Clinical Practice guidelines, governance and consent procedures were found to have substantially affected the intended simple nature of the trials. One qualitative study of 13 clinicians found that clinicians were generally positive about the principle of computerised trial recruitment (flagging during consultation). However, trials which did not include patients with acute illness were favoured. The second qualitative process evaluation interviewed 27 GPs about their actual experiences, including declining, recruiting and non-recruiting GPs. Opportunistic patient recruitment during a routine GP consultation was found to be the most controversial element. The actual experiences of recruiting patients during unscheduled consultation were generally more positive than the hypothetical views of GPs. Several of the recruiting GPs reported the process took 5 minutes and was straightforward and feasible on most occasions. Almost all GPs expressed their strong support for the use of EHRs for trials. Ten eLung participants were interviewed, all of whom considered it acceptable to be recruited during a consultation and to use EHRs for trials. CONCLUSIONS EHR point-of-care trials are feasible, although the recruitment of clinicians is a major challenge owing to the complexity of trial approvals. These trials will provide substantial evidence on clinical effectiveness only if trial interventions and participating clinicians and patients are typical of usual clinical care and trials are simple to initiate and conduct. Recommendations for research include the development of evidence and implementation of risk proportionality in trial governance and conduct. TRIAL REGISTRATION Current Controlled Trials ISRCTN33113202 and ISRCTN72035428. FUNDING This project was funded by the NIHR Health Technology Assessment programme and the Wellcome Trust and will be published in full in Health Technology Assessment; Vol. 18, No. 43. See the NIHR Journals Library website for further project information.

Use of the English urgent referral pathway for suspected cancer and mortality in patients with cancer: cohort study

Objective To assess the overall effect of the English urgent referral pathway on cancer survival. Setting 8049 general practices in England. Design Cohort study. Linked information from the national Cancer Waiting Times database, NHS Exeter database, and National Cancer Register was used to estimate mortality in patients in relation to the propensity of their general practice to use the urgent referral pathway. Participants 215 284 patients with cancer, diagnosed or first treated in England in 2009 and followed up to 2013. Outcome measure Hazard ratios for death from any cause, as estimated from a Cox proportional hazards regression. Results During four years of follow-up, 91 620 deaths occurred, of which 51 606 (56%) occurred within the first year after diagnosis. Two measures of the propensity to use urgent referral, the standardised referral ratio and the detection rate, were associated with reduced mortality. The hazard ratio for the combination of high referral ratio and high detection rate was 0.96 (95% confidence interval 0.94 to 0.99), applying to 16% (n=34 758) of the study population. Patients with cancer who were registered with general practices with the lowest use of urgent referral had an excess mortality (hazard ratio 1.07 (95% confidence interval 1.05 to 1.08); 37% (n=79 416) of the study population). The comparator group for these two hazard ratios was the remaining 47% (n=101 110) of the study population. This result in mortality was consistent for different types of cancer (apart from breast cancer) and with other stratifications of the dataset, and was not sensitive to adjustment for potential confounders and other details of the statistical model. Conclusions Use of the urgent referral pathway could be efficacious. General practices that consistently have a low propensity to use urgent referrals could consider increasing the use of this pathway to improve the survival of their patients with cancer.

Carbon in airway macrophages from children with asthma

Background Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. Methods AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (μm2) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. Results AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=−0.40, p<0.05, and rs=−0.44, p<0.01). PGE2 10−6 M, but not PGD2 10−6 M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10−6 M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). Conclusions Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.

Improving outcomes for people with COPD by developing networks of general practices: evaluation of a quality improvement project in east London.

Background:Structured care for people with chronic obstructive pulmonary disease (COPD) can improve outcomes. Delivering care in a deprived ethnically diverse area can prove challenging.Aims:Evaluation of a system change to enhance COPD care delivery in a primary care setting between 2010 and 2013 using observational data.Methods:All 36 practices in one inner London primary care trust were grouped geographically into eight networks of 4–5 practices, each supported by a network manager, clerical staff and an educational budget. A multidisciplinary group, including a respiratory specialist and the community respiratory team, developed a ‘care package’ for COPD management, with financial incentives based on network achievements of clinical targets and supported case management and education. Monthly electronic dashboards enabled networks to track and improve performance.Results:The size of network COPD registers increased by 10% in the first year. Between 2010 and 2013 completed care plans increased from 53 to 86.5%, pulmonary rehabilitation referrals rose from 45 to 70% and rates of flu immunisation from 81 to 83%, exceeding London and England figures. Hospital admissions decreased in Tower Hamlets from a historic high base.Conclusions:Investment of financial, organisational and educational resource into general practice networks was associated with clinically important improvements in COPD care in socially deprived, ethnically diverse communities. Key behaviour change included the following: collaborative working between practices driven by high-quality information to support performance review; shared financial incentives; and engagement between primary and secondary care clinicians.

Primary care delays in diagnosing cancer: what is causing them and what can we do about them?

Thomas Round, Liz Steed, Judith Shankleman, Liam Bourke and Liliana Risi Primary Care and Public Health Sciences, King’s College London, Capital House, London SE1 3QD, UK Centre for Primary Care and Public Health, Queen Mary University London, London, E1 2AB, UK Public Health Tower Hamlets, Mulberry Place, London E14 1BY, UK NHS Tower Hamlets Clinical Commissioning Group, Mile End Hospital, London E1 4DG, UK Corresponding author: Thomas Round. Email: thomas.round@kcl.ac.uk

Expectations for Antibiotics Increase Their Prescribing: Causal Evidence About Localized Impact.

Objective: Clinically irrelevant but psychologically important factors such as patients’ expectations for antibiotics encourage overprescribing. We aimed to (a) provide missing causal evidence of this effect, (b) identify whether the expectations distort the perceived probability of a bacterial infection either in a pre- or postdecisional distortions pathway, and (c) detect possible moderators of this effect. Method: Family physicians expressed their willingness to prescribe antibiotics (Experiment 1, n1 = 305) or their decision to prescribe (Experiment 2, n2 = 131) and assessed the probability of a bacterial infection in hypothetical patients with infections either with low or high expectations for antibiotics. Response order of prescribing/probability was manipulated in Experiment 1. Results: Overall, the expectations for antibiotics increased intention to prescribe (Experiment 1, F(1, 301) = 25.32, p < .001, &eegr;p2 = .08, regardless of the response order; Experiment 2, odds ratio [OR] = 2.31, and OR = 0.75, Vignettes 1 and 2, respectively). Expectations for antibiotics did not change the perceived probability of a bacterial infection (Experiment 1, F(1, 301) = 1.86, p = .173, &eegr;p2 = .01, regardless of the response order; Experiment 2, d = −0.03, and d = +0.25, Vignettes 1 and 2, respectively). Physicians’ experience was positively associated with prescribing, but it did not moderate the expectations effect on prescribing. Conclusions: Patients’ and their parents’ expectations increase antibiotics prescribing, but their effect is localized—it does not leak into the perceived probability of a bacterial infection. Interventions reducing the overprescribing of antibiotics should target also psychological factors.

The Role of Physicians’ First Impressions in the Diagnosis of Possible Cancers without Alarm Symptoms

Background. First impressions are thought to exert a disproportionate influence on subsequent judgments; however, their role in medical diagnosis has not been systematically studied. We aimed to elicit and measure the association between first impressions and subsequent diagnoses in common presentations with subtle indications of cancer. Methods. Ninety UK family physicians conducted interactive simulated consultations online, while on the phone with a researcher. They saw 6 patient cases, 3 of which could be cancers. Each cancer case included 2 consultations, whereby each patient consulted again with nonimproving and some new symptoms. After reading an introduction (patient description and presenting problem), physicians could request more information, which the researcher displayed online. In 2 of the possible cancers, physicians thought aloud. Two raters coded independently the physicians’ first utterances (after reading the introduction but before requesting more information) as either acknowledging the possibility of cancer or not. We measured the association of these first impressions with the final diagnoses and management decisions. Results. The raters coded 297 verbalizations with high interrater agreement (Kappa = 0.89). When the possibility of cancer was initially verbalized, the odds of subsequently diagnosing it were on average 5 times higher (odds ratio 4.90 [95% CI 2.72 to 8.84], P < 0.001), while the odds of appropriate referral doubled (OR 1.98 [1.10 to 3.57], P = 0.002). The number of cancer-related questions physicians asked mediated the relationship between first impressions and subsequent diagnosis, explaining 29% of the total effect. Conclusion. We measured a strong association between family physicians’ first diagnostic impressions and subsequent diagnoses and decisions. We suggest that interventions to influence and support the diagnostic process should target its early stage of hypothesis generation.

Prevalence and alternative explanations influence cancer diagnosis: An experimental study with physicians

Objective: Cancer causes death to millions of people worldwide. Early detection of cancer in primary care may enhance patients’ chances of survival. However, physicians often miss early cancers, which tend to present with undifferentiated symptoms. Within a theoretical framework of the hypothesis generation (HyGene) model, together with psychological literature, we studied how 2 factors—cancer prevalence and an alternative explanation for the patient’s symptoms—impede early cancer detection, as well as prompt patient management. Method: Three hundred family physicians diagnosed and managed 2 patient cases, where cancer was a possible diagnosis (one colorectal cancer, the other lung cancer). We employed a 2 (cancer prevalence: low vs. high) × 2 (alternative explanation: present vs. absent) between-subjects design. Cancer prevalence was manipulated by changing either patient age or sex; the alternative explanation for the symptoms was manipulated by adding or removing a relevant clinical history. Each patient consulted twice. Results: In a series of random-intercept logistic models, both higher prevalence (OR = 1.92, 95% confidence interval [CI 1.27, 2.92]) and absence of an alternative explanation (OR = 1.70, 95% CI [1.11, 2.59]) increased the likelihood of a cancer diagnosis, which, in turn, increased the likelihood of prompt referral (OR = 22.84, 95% CI [16.14, 32.32]). Conclusions: These findings confirm the probabilistic nature of the diagnosis generation process and validate the application of the HyGene model to early cancer detection. Increasing the salience of cancer—such as listing cancer as a diagnostic possibility—during the initial hypothesis generation phase may improve early cancer detection.

Attitudes to participating in a birth cohort study, views from a multiethnic population: a qualitative study using focus groups

Recruitment to birth cohort studies is a challenge. Few studies have addressed the attitudes of women about taking part in birth cohort studies particularly those from ethnic minority groups.

Calling time on the 10-minute consultation

I read with interest the recent BJGP editorial on ‘Calling time on the 10-minute consultation’.1 As a recently qualified GP working in one of the most deprived and ethnically diverse areas of the UK the concept of a one size fits all 10-minute consultation seems woefully outdated. As an individual practitioner I of …