Express authorization of medicines, a double-edged sword

Cristina Roure

The approval of Aducanumab by accelerated route, by the Food and Drug Administration (FDA), for the treatment of Alzheimer's has been carried out against the unanimous opinion of its Advisory Committee on this matter, which has raised enormous dust. It is the first drug that attacks a supposed cause of the disease instead of its symptoms and has generated great expectations in a therapeutic area in which the gap is notable.

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.

Initiatives to define a patient-centred research agenda

Glòria Galvez
 

By Society of Hospital Medicine

Despite the strong impact that the results of clinical research have on the health and quality of life of patients, the contributions they make remain anecdotal and do not go beyond participating as passive subjects in clinical trials. This, together with the practice of opportunistic strategies such as calling patients at the last moment to give their impressions of their participation, makes it necessary to move towards a new model of biomedical research in which, in addition to carrying out pharmacological studies, it seeks to respond to unresolved questions that would undoubtedly improve the patient experience.

Health expectations influence the result

Andrés Fontalba
 

In search of the perfect woman, Pygmalion fell in love with his Galatea statue. Such was his wish, according to Ovid's account in The Metamorphoses, that the statue became human. When the Pygmalion effect occurs, the expectations we have influence our behaviour and our way of acting is precisely what causes the expected result. Our own beliefs also influence other people and thus we seek that our expectations become true with behaviours that tend to confirm them. This effect is also known as "self-fulfilling prophecy" and it means that we will do everything possible to make what we believe will happen finally come true.

Nutrition and health: confusion is served

Cristina Roure

Red and processed meat, so reviled for years in all healthy eating guides, is back to happy days. Recently, the United States Department of Agriculture abolished the initiative promoted by Michelle Obama that proposed the inclusion of fresh fruits and vegetables in school cafeterias. The reason was to defend the freedom of the individual and the educational centres to offer a more nutritious meal following the preferences of the American population.

Bad science, new chapters

Jordi Varela
Editor

In July of last year I commented on a work by Paul Glasziou and Iain Chalmers that concluded that taking into account methodological shortcomings, unpublished studies and poorly explained ones, the waste of biomedical research could be of the order of 85%. According to these authors, only 15% of what is investigated reaches the clinic in conditions of quality and appropriate communication. A little over a year later, other sources insist that biomedical research, in general terms, does not show signs of recovery and, to make it understandable, I will follow the same scheme that I used in the post I have quoted.

Lessons from the opioid crisis, a case of overtreatment with devastating consequences

Cristina Roure
 

If you are regulars of American series such as House, The Affair or This is us, you will be familiar with the classic protagonist who, after an episode of acute pain, ends up becoming addicted to prescription opioids such as Vicodin®, OxyContin® or Percocet®. Do not think that this is a writer’s exaggeration.

In 2015, life expectancy in the United States changed the trend and began to decline for the first time since the First World War. Among the causes, the epidemic of deaths from opioid overdoses, which multiplied by six between 1999 and 2017 (1), surpassing deaths associated with AIDS at its worst or those related to the Vietnam War. The epidemic was declared a national emergency by the United States Department of Health in 2017 and, despite the campaign deployed to combat it (2), 130 people still die in that country every day from opium overdose. If you are interested in the subject and want to delve into it, read the supplement that Nature dedicated to it in September last year.

Centralisation of complex surgery: clear, obscure and proposals

@varelalaf

A large group of European and North American surgeons have published in Annals of Surgery a review of the difficulties of centralising complex surgery around the world. The complex issue has multiple actors, starting with governments and respective funding models and continuing by the hospitals, the doctors involved and their corresponding scientific societies. It is surprising, however, that patients rarely appear in such discussions.

Precision medicine, hope or hype?

Cristina Roure

Fifteen years after the human genome has been deciphered, after 3 billion dollars and after 13 years of intense network research, the cost of sequencing the entire genome has been reduced a thousand times and more than 20 million people already get concrete results. In a few weeks, from a simple saliva sample, these people will receive comprehensive information about their genetic material for less than $100 thanks to companies such as 23andMe or Ancestry. In the United States, through an alliance between Genomind and the Albertsons pharmacy office chain, patients treated with psychoactive drugs can receive advice from their pharmacist so that their doctor prescribes a pharmaceutical-genetic test and perform it in the same pharmacy office. It’s spectacular that a series of emerging diagnostic technologies target healthy people to predict or detect diseases early: immune footprint to predict various types of cancer and infectious diseases, biomarkers for Alzheimer's disease, or exhaled breath tests for early detection of lung cancer.

Medicine, values and communication

Salvador Casado

Modern medicine has achieved a spectacular development in the last century in parallel with the rest of society. Spurred on by science and technology it has managed to overcome ambitious goals and shines proudly on the basis of its achievements. Unfortunately, there is a long shadow that contains burdens and threats. Inequalities in health, overdiagnosis and overtreatment, iatrogeny, the progressive dependence of citizens on health systems are increasingly present realities.

Illustration by Paula Alvear, from the poems Arconte Enfurecido

On the other hand, private health systems and the enormous conglomerates of pharmaceutical and technological industries based on profit seek interests that are increasingly distant from the common good. In the face of these interests, public health systems are slowly collapsing due to under-funding, cutbacks and the chronic overloading of their professionals. Everyone agrees on the complexity of managing alternatives but no one dares to implement them. Meanwhile, the public health systems are melting like butter as services are outsourced, professionals working conditions get worse or units are reconverted and closed (Public Health and others).

Escape the biomedical bubble

Cristina Roure

One of the most recurrent citation in clinical management is the Porterian concept of health value, which must be established based on the interest of the patient and not the rest of agents, read professionals, managers, researchers, administration, biomedical industry, etc. According to this concept, the ultimate purpose of research and innovation in health should be to provide maximum benefit to patients and society. However, as I commented in my last blog post, I often prioritized research and the real needs of patients, but society goes in different ways.

For a research based on value. The failed model of antibiotics

Cristina Roure

As we have commented on some occasion in this blog, neither the price nor the volume of investment in R&D of the medicines corresponds to the value they provide. Antibiotics, along with vaccines, have saved millions of lives, have allowed to address challenges such as transplants and complex surgeries with guarantees of success and, if this were not enough, they also add enormous value to the productivity of the agricultural sector.

It’s estimated that the waste in biomedical research reaches 85%

In 2014, following concerns over the poor quality of biomedical research, The Lancet published a series of 5 articles analysing the scope of the problem and proposing solutions and as a result of this Reward Alliance was born, a platform that aims to defend the value of the research, from which I have extracted the scandalous figure of 85% and, according to Paul Glasziou and Iain Chalmers, two of the leaders of the movement, the volume of money squandered by biomedical research could reach 170 billion dollars annually, an amount higher than Hungary's gross domestic product. The two authors, who already predicted this figure in 2009, argue that this amount comes from an accumulation of up to three times 50%.

Cancer research: little science, big data or big science

Apparently, the duration and costs of clinical trials of new oncological drugs could be reduced if surrogate measures, such as tumour reduction or time to progression, were to be used instead of survival, but a meta-analysis of 146 clinical trials of colorectal cancer and 191 of lung cancer found that only 10-16% of survival was explained by these variables; obviously a poor correlation. On the other hand, there is the question of the methodology used. A review of 43 studies found that, in 81% of the cases, promising results from phase II (without a control group) failed to transfer to phase III (double-blind randomized trial). The latter is another finding unfavourable to the rush with which many oncological drugs are introduced in the market. Perhaps it’s for this reason that, in an observation of 94 articles on the subject, Abola and Prasad have discovered that in half of them, the editors had resorted to adjectives of the type: miraculous, revolutionary, innovative, wonderful, transformative, etc...

The laws of medicine

Siddhartha Mukherjee, oncologist, researcher and professor at the University of Columbia, is the author of a small essay, The Laws of Medicine: field notes from an uncertain science (2015), which I found interesting enough to recommend to clinicians who desire to think a little more about what they do. "In the medical school," says the author, "they taught me a lot of facts, but they did not prepare me to navigate the immense spaces between these facts. Right now I could write a thesis on the physiology of sight, but I feel lost when I try to understand the conniving network that makes a man, who was prescribed home oxygen, give a false address to the service providers, embarrassed (I later learned), because he lived on the street."

Treatments, tested

The other day, Xavier Bonfill and Iain Chalmers presented the Catalan edition of the book Testing Treatments. Better Research for Better Healthcare. This caught my attention and after 12 years of delay, I was motivated to read the work. It’s necessary to clarify that in 2006, the year of its first edition; I was a hospital CEO and had neither the head nor the time for this. Maybe one day we will have to talk about what the executives read. Be that as it may, this text is considered one of those that have laid the foundations of modern clinical management, which concentrates its focus on effectiveness, a goal as coveted as it is difficult (1).

Journalist Nick Ross, in the presentation of the first edition of the book, wrote: "This book is good for health; it shines light on the mysteries of how decisions about life and death are made. It goes to show how these criteria are generally lacking and it challenges doctors from around the world to change their ways.” On the other hand, Ben Goldacre, in the prologue of the second edition (2011), provides a really interesting quote: "The true purpose of the scientific method is to make sure that nature doesn’t mislead us into thinking that we know something that we don’t really know".

Vinay Prasad: Why is 40% of clinical practice wrong?

On May 18, Vinay Prasad offered a conference in Barcelona as part of the 5th "Right Care" Conference of the Clinical Management Section of the Catalan Society of Health Management (SCGS), where we had the opportunity to invite him to explain why he had created (with Adam Cifu and other collaborators) the list of 146 clinical practices that would have to be reversed and what are the criteria they had been used.

What is medical reversal?

According to Prasad, a medical reversal is the need to stop a clinical activity because a well-done study, usually a clinical trial with finalist indicators, shows that in fact, the desired results are not achieved, or that the adverse effects do not compensate the benefits. The speaker gave some very diverse examples, such as the Swan Ganz catheterization to monitor the hemodynamic balance of patients in shock, the hormonal treatment for post-menopausal women in order to reduce coronary or cerebral vascular risk and the placement of coronary stents in patients with stable angina to reduce the risk of infarction, increase survival or even to delay the effort angina. In all three examples, consistent clinical trials have shown that these were clinical activities that, in practice, did not meet the set objectives, and in addition had side effects, which were not unimportant.

Experience versus evidence, regarding Ian Harris

Professor Ian Harris, author of the book, "Surgery, the ultimate placebo", is a traumatologist who directs a research unit focused on the results of surgical practice in Sydney. Harris says in the book's introduction: "Lack of evidence allows surgeons to practice techniques for the simple reason that they have always been done, because they learned them from their mentors, because they are convinced that it works or simply because it does everybody. It's easier to have no problems if you behave like most colleagues, my argument, says the author, is that trusting tradition and perceptions often leads, in terms of clinical effectiveness, to unconvincing results."

The fallibility of scientists

Nature has echoed the professional debate about the intrinsic quality of scientists’ work, in a dynamics of self-criticism comparable to what is taking place, in similar terms, in the clinical world. Scientists are also fallible, says the article writer and therefore, should enhance the mechanisms of self-criticism, rather than enrol in self-deception.

John Ioannidis, Meta-Research Innovation Center at Stanford, says scientists should work harder to understand the biases of their human fallibility if they want to overcome the crisis of confidence generated by the poor reproducibility of research results. And to illustrate his words, Ioannidis offers three examples: a) from a selection of one hundred psychology studies, only the results of just over a third of the work could be replicated, b) a group of Amgen researchers only succeeded in reproducing 6 of the results of 53 reference studies in the field of oncology and haematology, and c) the Ioannidis team itself was able to replicate completely only 2 of the 18 gene expression studies based on microarrays (DNA chips).

Value Based Medicine (VBM)

Evidence-based medicine (EBM), after 25 years, has generated substantial advances in research methodology and has made it possible to distinguish more clearly between good and bad treatments, to identify biases of any order and even evidence of conflicts of interest between research and industry. However, a group of English authors (The importance of values in EBM, Kelly MP 2016) believes that, despite the uncontested advances, EBM has put too much focus on the technical aspects and has forgotten that values ​​have a lot of influence at all stages of the evidence-building processes.

What do we mean when we talk about values?

Science strives to understand the world as it is, but conversely, values ​​are what humans reflect upon. Seen this way, the conflict is served and, therefore EBM should learn to navigate better between these two waters according to the authors of the article quoted below, "Values may act as heuristics – shortcuts in our thinking of which we are barely aware – which get us to quick answers to complicated problems. They form the lens through which we perceive and act on our world. Values are often tricky to pin down because they are such a pervasive part of things we take for granted. A necessary first step towards achieving this is to make our values as explicit as we can, so that we can reflect on them individually and deliberate on them collectively".