When we move cancer drugs from the second or third to the first line of treatment: what lessons can we learn from KEYNOTE-177 and JAVELIN-100
If the current standard of care is to give a new cancer drug as the second or third treatment option for a patient and there is interest in moving the drug to the front-line setting, how should we design and evaluate the study? Two recent examples can help us make sense of this question. The recent KEYNOTE-177 Study1 evaluated pembrolizumab in microsatellite-instability-high (MSI-high) advanced colorectal cancer found that front-line use of pembrolizumab is associated with an improved progression-free survival (PFS), median 16.5 months versus 8.2 months, compared with standard chemotherapy. Similarly, JAVELIN-1002 found th...
Source: Evidence-Based Medicine - May 24, 2022 Category: Internal Medicine Authors: Kim, M. S., Prasad, V. Tags: EBM opinion and debate Source Type: research
Getting the COVID-19 vaccine as a transplant patient
Getting the vaccine appointment ‘Yes! I am fully vaccinated’, I said to myself. The thrill, the excitement, coupled with too many other emotions to describe came swelling over me. I was also all alone, waiting in a room with others who had recently received their first or second dose of a COVID-19 mRNA vaccine. I could sense a feeling of cautious joy in the room as I looked around at others also sitting with their masks on. At 39 years of age, I guessed that I was the youngest person in the room. I felt ‘chosen’ and privileged to be among the first to be vaccinated. Several weeks before, when my doc...
Source: Evidence-Based Medicine - May 24, 2022 Category: Internal Medicine Authors: Mittelman, M. Tags: COVID-19 Patient voices Source Type: research
'Diagnostic downshift: clinical and system consequences of extrapolating secondary care testing tactics to primary care
Numerous drivers push specialist diagnostic approaches down to primary care (‘diagnostic downshift’), intuitively welcomed by clinicians and patients. However, primary care’s different population and processes result in under-recognised, unintended consequences. Testing performs poorer in primary care, with indication creep due to earlier, more undifferentiated presentation and reduced accuracy due to spectrum bias and the ‘false-positive paradox’. In low-prevalence settings, tests without near-100% specificity have their useful yield eclipsed by greater incidental or false-positive findings. ...
Source: Evidence-Based Medicine - May 24, 2022 Category: Internal Medicine Authors: Sajid, I. M., Frost, K., Paul, A. K. Tags: EBM analysis Source Type: research
NICE rapid guidelines: exploring political influence on guidelines
The National Institute for Health and Care Excellence (NICE) has been presented as politically independent, asserting it is free from industry influence and conflicts of interest so that its decisions may be led by evidence and science. We consider the ways in which soft political factors operate in guideline development processes at NICE such that guidelines are not truly led by science. We suggest that while NICE procedures explicitly incorporate scientific principles and mechanisms, including independent committees and quality assurance, these fail to operate as scientific practices because, for example, decisions may o...
Source: Evidence-Based Medicine - May 24, 2022 Category: Internal Medicine Authors: McPherson, S., Speed, E. Tags: EBM analysis Source Type: research
Publication by association: how the COVID-19 pandemic has shown relationships between authors and editorial board members in the field of infectious diseases
During the COVID-19 pandemic, the rush to scientific and political judgements on the merits of hydroxychloroquine was fuelled by dubious papers which may have been published because the authors were not independent from the practices of the journals in which they appeared. This example leads us to consider a new type of illegitimate publishing entity, ‘self-promotion journals’ which could be deployed to serve the instrumentalisation of productivity-based metrics, with a ripple effect on decisions about promotion, tenure and grant funding, but also on the quality of manuscripts that are disseminated to the medic...
Source: Evidence-Based Medicine - May 24, 2022 Category: Internal Medicine Authors: Locher, C., Moher, D., Cristea, I. A., Naudet, F. Tags: General Medicine, COVID-19 EBM analysis Source Type: research
Developing future leaders in evidence-based medicine: the inaugural David Sackett Fellowship
David L Sackett, widely described as the ‘father of evidence-based medicine (EBM)’1 was a transformative figure in 20th century health research and education. His career spanned three distinct phases: as a clinician, as a clinical trialist and as a clinical epidemiologist, most of it at McMaster University in Hamilton, Ontario, Canada, where he was the founder (in 1967, at the age of 32) of the Department of Clinical Epidemiology and Biostatistics. That department remained his professional home until 1994 when he moved to the University of Oxford for 5 years to found the Centre for Evidence-Based Medicine (CEBM...
Source: Evidence-Based Medicine - May 24, 2022 Category: Internal Medicine Authors: Gill, P. J., ONeil, B., Richards, G. C. Tags: Editorials Source Type: research
Evaluating the performance of high-sensitivity troponin-T in the emergency department during the COVID-19 pandemic
To reduce emergency department (ED) chest pain observation and admission rates, a multidisciplinary task force designed and implemented a triage protocol using quantitative symptom scoring (HEART score) and biomarkers for myocardial damage. High-sensitivity troponin-T (hs-TnT) has been shown to be an effective tool in diagnosing patients with suspected acute coronary syndrome (ACS) in the ED.1 2 The protocol risk stratified patients by HEART score and hs-TnT into low risk (HEART score 0–3 and normal hs-TnT in two separate measurements in 2-hour intervals), intermediate risk (HEART score 4–6 and hs-TnT <100 n...
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Alsaad, A. A., Wang, E., Lee, H., Lampert, M., Krause, P., Tommaso, C., Mishkel, G., Erwin, J., Boyle, C., Donlan, S., Smiley, J., Halasyamani, M. Tags: COVID-19 Letters Source Type: research
Low carbohydrate diets should NOT be recommended for patients with familiar hypercholesterolaemia
Diamond et al1 have questioned the efficacy of low-saturated fat, low-cholesterol diet to reduce LDL cholesterol in individuals with familiar hypercholesterolaemia (FH) and suggested that these patients be introduced to low carbohydrate diets (LCD). There are several problems with their suggestions, the main one is addressed in this letter. Evidence from animal and human studies showed that LCD, which usually are also high in protein (LCHP) and/or fat, exacerbate atherosclerosis independently of ‘significant alterations in traditional atherogenic serum lipids, serum inflammatory markers and histological indicators of...
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Pawlak, R. Tags: Letters Source Type: research
Correlation between the use of statins and COVID-19: what do we know?
The COVID-19 global pandemic caused by the new Coronavirus SARS-CoV-2 represents a challenge for the health of humanity, with few precedents. The new Coronavirus SARS-CoV-2 (COVID-19) is the cause of severe acute respiratory syndrome (SARS), a severe form of viral pneumonia.1 The virus spread rapidly from China to the rest of the world in a very short time and with considerable intensity and severity creating a ‘global emergency’. Studies have shown that angiotensin-converting enzyme 2 (ACE-2) is the entry receptor of SARS-CoV-2 into host cells. Type II pneumocytes represent 83% of the cells expressing ACE-2 in...
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Vitiello, A., La Porta, R., Ferrara, F. Tags: COVID-19 Letters Source Type: research
Dichotomies: often desired, sometimes dubious and always requiring due diligence
I recently discussed1 some common difficulties with employing continuous outcomes and how established conversion methods might help. Space limits precluded some worthwhile considerations, and I highlight a few here. Although continuous outcomes carry certain inferential considerations,1 this is not an insurmountable ‘problem’ per se. An estimated proportion of people who will achieve some degree of effect may seem easier to understand. However, one must respect: (1) what such estimation entails when the underlying data are continuous, and (2) that continuous data are not just irrelevant or inapplicable; they ma...
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Mayer, M. Tags: Letters Source Type: research
Adherence in leading medical journals to the CONSORT 2010 statement for reporting of binary outcomes in randomised controlled trials: cross-sectional analysis
Clinicians and lay people tend to overestimate the effectiveness of a treatment when only the relative effect is presented, particularly if the relative effect is large, but the absolute effect is small. In recognition of this problem, item 17b of The Consolidated Standards of Reporting Trials (CONSORT) 2010 statement stipulates authors present both absolute and relative effects for binary outcomes in randomised controlled trials (RCTs). Adherence to item 17b and the effect of differing levels of CONSORT endorsement by journals on adherence is not well known. We assessed the extent to which item 17b is adhered to in 258 RC...
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Nunan, D., Watts, I., Kaji, F. A., Hansjee, S., Heneghan, C. Tags: Research methods and reporting Source Type: research
Framework for the synthesis of non-randomised studies and randomised controlled trials: a guidance on conducting a systematic review and meta-analysis for healthcare decision making
Conclusion: Our framework augments existing guidance on assessing the quality of NRS and their compatibility with RCTs for evidence synthesis, while also highlighting potential challenges in implementing it. This manuscript received endorsement from the International Society for Pharmacoepidemiology. (Source: Evidence-Based Medicine)
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Sarri, G., Patorno, E., Yuan, H., Guo, J., Bennett, D., Wen, X., Zullo, A. R., Largent, J., Panaccio, M., Gokhale, M., Moga, D. C., Ali, M. S., Debray, T. P. A. Tags: Open access, General Medicine Evidence synthesis Source Type: research
Association of study design features and treatment effects in trials of chronic medical conditions: a meta-epidemiological study
Conclusion
The meta-epidemiological study did not demonstrate a clear pattern of association between risk of bias indicators and treatment effects in RCTs in chronic medical conditions. The unpredictability of the direction of bias emphasises the need to make every attempt to adhere to blinding, allocation concealment and reduce attrition bias.
Trial registration number
Not applicable. (Source: Evidence-Based Medicine)
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Wang, Z., Alahdab, F., Farah, M., Seisa, M., Firwana, M., Rajjoub, R., Saadi, S., Jawaid, T., Nayfeh, T., Murad, M. H. Tags: Original research Source Type: research
Effect of spin in the abstract of a randomised controlled trial on physiotherapists perception of treatment benefit: a randomised controlled trial
Conclusions
Removal of spin in the abstract of RCT reporting statistically non-significant results have medium effect in improving physiotherapists’ accuracy of interpretation of study results. Spin contributes to clinicians’ positive perception about the benefit of experimental intervention tested in the trial despite the evidence showing no superiority of experimental intervention.
Trial registration number
CTRI/2020/02/023557. (Source: Evidence-Based Medicine)
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Khanpara, H., Prakash, V. Tags: Original research Source Type: research
Short and long-term psychosocial consequences of participating in a colorectal cancer screening programme: a matched longitudinal study
Conclusions
The study showed that there are both short-term and long-term psychosocial consequences associated with receiving a no abnormalities result or being diagnosed with polyps. The consequences were worst for individuals diagnosed with medium-risk and high-risk polyps. (Source: Evidence-Based Medicine)
Source: Evidence-Based Medicine - March 23, 2022 Category: Internal Medicine Authors: Malmqvist, J., Siersma, V. D., Hestbech, M. S., Bang, C. W., Nicolaisdottir, D. R., Brodersen, J. Tags: Open access Original research Source Type: research
