Make Evidence-Based Medicine Great Again!

Cristina Roure
 

“Make Evidence-Based Medicine Great Again!” is the provocative title of a conference that Dr. Domenico Pagano delivered at the 56th Congress of the American Society for Cardio-thoracic Surgery, calling for the need to restore professionalism, integrity, and trust in data and evidence in medicine. The conference is long, it lasts 55 minutes, but Pagano makes a brilliant presentation on the increasing manipulation that has led us to the swamp in which evidence-based medicine (EBM) currently inhabits.

“Clinical trials are possible thanks to the generosity and altruism of patients who trust that their participation will lead to an advance in science that will benefit other patients in the future; we should not betray that trust.”

The subject is old and some of you must have read the excellent book Malignant, by Vinay Prasad,(1) or Better Doctors, Better Patients, Better Decisions, by Gerd Gigerenzer and JA Muir Gray,(2) and how well they explain the contamination and perversions of the knowledge management chain in medicine and, in the case of Prasad, in oncology in particular. Both are excellent and recommendable, but I often think that the scientific community, in general, calls them a certain nihilism, accepts the situation as something inevitable, and chooses to adapt and live comfortably in the swamp without anything changing.

"The knowledge generated today is the legacy we leave to future generations of doctors and patients. It's our responsibility to ensure that we come up with the best answers we can: relevant, rigorous, and free of bias."

We might think that if the necessary skills in critical evaluation of the evidence are acquired, the problem will be solved, but critical evaluation implies a careful reading of the methods and results. I assure you that, leaving aside the most obvious, it's difficult to detect the innumerable and subtle biases that permeate the medical literature we consume. Given the difficulty of going into such technical aspects, most choose to ignore them and go directly to read the conclusions of the authors or the discussion. Do not think that this is negligence or carelessness: only 19% of doctors say they use EBM techniques in clinical practice. (3) Gordon Guyatt himself, one of the fathers of EBM, acknowledges that the perspective has changed and that to be fully competent in the evaluation of the evidence requires an earnest postgraduate training that few prioritize and that, if they acquire it, is difficult to maintain and apply.(4) More realistic approaches are needed, based on in secondary sources of evidence such as reliable clinical practice guidelines. I recommend an interesting podcast in which Gordon Guyatt talks with Victor Montori about the misleading presentation of clinical trial results.

We should remember that evidence is never enough to guide person-centered practice and that patients' values and preferences are always crucial. The right choice is not universal. The clinician must know the applicability of the results to each patient, as well as the magnitude of the benefits, harms, and burdens associated with each of the alternatives, and discuss them with the patients.

"Clinicians can't acquire the 68 core competencies in EBM that are needed to carry out a good critical evaluation of primary sources, but they must acquire some basic competencies on the applicability of clinical practice guidelines to shared decision-making in each patient."

In the video below, Montori explains how to incorporate EBM into patient care.

Beyond clinical practice guidelines, other tools can be valuable in decision-making. The Clinical Benefit Magnitude Scale of the European Society for Medical Oncology (ESMO-MCBS) is a tool developed to quantify the clinical benefit of anticancer drugs whose objective is to identify treatments with a relevant clinical benefit for patients and distinguish them from those that offer a marginal benefit.

The scale assumes the validity of the methodology and implementation of clinical trials, but, after six years of experience, the ESMO is now considering how to prevent clinical trials with methodological biases or poorly implemented, which overestimate the real benefit, from conducting to erroneous conclusions about the value of the clinical benefit that the drug provides and thus pervert the objective of the tool.(5) Seven sources of bias have been identified, unaddressed in the current version of the ESMO-MCBS scale, with suggested fixes for future versions. The article details the seven sources of bias, but for non-specialists in oncology, all of them are demonstrated with clear examples in the book Malignant, by Vinay Prasad.

Clinical trials are the bricks with which EBM is built. If the "construction material" is defective, it's impossible for the "buildings" to be robust and for decisions to be the best for patients and society. More initiatives such as ESMO's are required to "select the raw material" with which they build the instruments that they put at the service of clinicians and patients. Only in this way will we be able to recover the spirit of the EBM and, in the words of Domenico Pagano, "make it great again".

Bibliography

1. Vinayak K Prasad. Malignant: How Bad Policy and Bad Evidence Harm People with Cancer. Johns Hopkins University Press, Baltimore 2020. ISBN: 9781421437637.
2. Gigerenzer & JA Muir Gray. Better Doctors, Better Patients, Better Decisions. Envisioning Health Care 2020. Gerd The MIT Press 2011. ISBN: 9780262016032.
3. Lafuente-Lafuente C, Leitao C, Kilani I, et al. Knowledge and use of evidence-based medicine in daily practice by health professionals: a cross-sectional survey. BMJ Open 2019;9:e025224. 
4. Tikkinen KAO, Guyatt GH. BMJ Evidence-Based Medicine Epub ahead of print: [2 de juliol 2021]. doi:10.1136/ bmjebm-2020-111542. 
5. Gyawali B, de Vries EGE, Dafni U, Amaral T, Barriuso J, Bogaerts J, Calles A, Curigliano G, Gómez-Roca C, Kiesewetter B, Oosting S, Passaro A, Pentheroudakis G, Piccart M, Roitberg F, Tabernero J, Tarazona N, Trapani D, Wester R, Zarkavelis G, Zielinski C, Zygoura P, Cherny NI. Biases in study design, implementation, and data analysis that distort the appraisal of clinical benefit and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) scoring. ESMO Open. 2021 Jun;6(3):100117. doi: 10.1016/j.esmoop.2021.100117. Epub 2021 Apr 20. PMID: 33887690; PMCID: PMC8086024.