On the subject of methodology, the COVID 19 pandemic has stimulated a lot of discussion about design of clinical trials,
from this came our idea to highlight essential methodological concepts.
ON METHODOLOGY FUNDAMENTALS
In order to become more familiar with methodological issues the Cochrane Neurological Sciences Field decided to interview two experts in Neurology and Clinical methodology, both from the world of Stroke, International Clinical Trials and Cochrane, on various topics.
The Methodology Fundamentals are aimed primarily at young people, but can also be particularly useful to health professionals who wish to reorganize their knowledge in the methodological field.
We hope that these brief and informative discussions will tempt readers to further investigate the issues proposed, to this end we will select and attach papers that help to highlight the topics at hand.
Who are the experts?
Stefano Ricci - Editor, Cochrane Stroke Group, Perugia, Italy, and
Peter Sandercock - Emeritus Professor of Medical Neurology, University of Edinburgh, UK.
What are the Methodological Questions?
1) When are observational studies enough?
2) Why RCTs are better than observational studies?
3) What kind of RCTs are needed today?
4) Why it is so difficult to plan and arrange large pragmatic trials?
5) What regulatory authorities should modify to allow for the realisation of these kind of trials?
6) How can we ensure that clinical research is done where the results will eventually be applied?
The answers to these questions are the result of discussions between the two experts:
Q1: When are observational studies enough?
Observational studies are extremely useful and indeed irreplaceable in various relevant settings
a) Evaluation of epidemiological characteristics of a disease (e.g. how common is the condition? what is its prognosis? What are the risk factors?).
b) Evaluation of the external validity of a trial result.
c) Planning a trial. Estimate the effects of a treatment from observational epidemiology.
To give an Example: an observational study shows that an increase of “Y” mmHg in Systolic Blood Pressure is associated with an X% increase in the risk of stroke. In a randomized trial we can use this information to evaluate if the administration of a drug “A” lowering the BP by “Y” mmHg reduce the risk of stroke compared to control. Is the reduction that we expect to find, confirmed from the results of the trial? And if it is not confirmed, what are the reasons for this difference?
d) Putting the results of a treatment trial in clinical context, including the so-called phase 4 studies (mostly to evaluate side effects).
The role of observational studies, in these specific fields of medicine, cannot be underestimated; however, they cannot substitute randomized control trials when the aim of the study is to evaluate the effect of a new treatment on a specific outcome. This is because in modern medicine the problem is not to pick up the large effect of a treatment (for which no RCT is indeed needed) but a relatively moderate difference, which however -in terms of absolute effect- would modify the outcome of hundreds of thousands of patients in the world. In fact, a 3 or 4% absolute difference in death and disability in acute stroke looks like a modest result, but if that treatment were largely applied then a huge number of patients would benefit from it.
If our aim is to test efficacy, we cannot rely on non-randomized observational studies of therapy because this kind of study is prone to many biases, including selection and attrition bias, which can completely distort the result. So, let’s give observational studies their merits, but not give them more room than they actually deserve.
For further reading:
- Collins R, MacMahon S. Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials. Lancet 2001; 357: 373
- MacMahon and Collins, Lancet February 10, 2001, page 455.
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Raccolta Speciale: Coronavirus (2019-nCoV): evidenze per la terapia intensiva
L'epidemia di Coronavirus del 2019 è stata dichiarata un'emergenza globale di sanità pubblica dall'Organizzazione Mondiale della Sanità (OMS) lo scorso 30 gennaio 2020.
L'OMS sta ora lavorando a stretto contatto con esperti globali, governi e partner vari per espandere rapidamente le conoscenze scientifiche su questo nuovo virus, per tracciarne la diffusione e la virulenza e fornire consulenza a paesi e individui sulle misure per proteggere la salute e prevenire la diffusione del contagio.
Cochrane ha pubblicato oggi una Raccolta Speciale di Revisioni Sistematiche: Coronavirus (2019-nCoV): prove rilevanti per la terapia intensiva.
Questa Raccolta Speciale della Cochrane Library mette insieme le più rilevanti revisioni Cochrane per la gestione delle persone ricoverate in ospedale con gravi infezioni respiratorie acute. Comprende le revisioni di tre gruppi Cochrane, parte della Rete Acute and Emergency Care, che informano il processo decisionale in materia di salute relativo alle attuali raccomandazioni dell'OMS per l'epidemia di Coronavirus del 2019.
La raccolta verrà riesaminata man mano che la situazione cambia per garantire una pertinenza costante. Verranno raccolte separatamente le revisioni sistematiche relative alla prevenzione e alle misure di controllo delle infezioni.
Leggi la Raccolta Speciale Cochrane completa: Coronavirus (2019-nCoV): evidence relevant to critical care
Per saperne di più: Rete Cochrane Acute and Emergency Care
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This site is a source of useful information for people around the world who are involved with or interested in the practice of evidence-based neurology. We function as a link between clinicians, trainees, consumers, carers, policy-makers and Cochrane in the area of neurology.
The Cochrane Neurological Sciences Field is an entity of Cochrane, an international not-for-profit organization made up of more than 36.000 people around the world who work to promote evidence-based approaches to medicine.
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The primary aims and activities of the Cochrane Neurological Sciences Field include the following:
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