Dix conseils pour déceler le vrai du faux sur les articles de pharmacologie (sociale)

Petite leçon de décryptage d’un article médical

Publié par Luc Perino, médecin généraliste, humeur du 18/03/2019

Les sciences de la santé étant les plus faciles à corrompre, voici dix points devant susciter la méfiance, lors de la lecture d’un article parlant d’un médicament dans la presse générale.

  1. S’il est dit que la maladie concernée est sous-diagnostiquée ou diagnostiquée trop tardivement, l’article est probablement lié à des conflits d’intérêts ou sous influence directe de l’industriel. Manipuler l’opinion par la nécessité d’un diagnostic précoce est très efficace, car conforme à l’intuition populaire.
  2. S’il est question de « fléau du siècle », il faut vérifier si le fléau correspond à la maladie citée. Dire que le cancer est un fléau n’a pas de pertinence pour parler de certains cancers (prostate, col de l’utérus, mélanosarcome) dont chacun a un faible poids dans la mortalité. En outre, la grande fréquence d’une maladie ne signifie pas que l’article qui en parle soit pertinent. Cela devrait plutôt indiquer l’échec de ceux qui en ont la charge.
  3. Lorsqu’il s’agit d’une étude en cours, on peut cesser la lecture dans l’attente de résultats concrets. Car les échecs des études médicamenteuses sont généralement passés sous silence, contrairement aux échecs de la fusée Ariane qui sont tous mentionnés.
  4. Lorsque l’article surexploite le mythe du progrès. Vanter des succès historiques n’est pas suffisant pour anticiper un succès futur. Particulièrement dans le domaine de la santé.
  5. Lorsque l’article se résume à un ou plusieurs témoignages de cas individuels, cela ne suffit pas à établir une vérité médicale. Que ce soit l’exploitation d’un seul incident pour dénigrer un vaccin, ou la satisfaction d’un seul patient pour clamer l’efficacité d’un médicament.
  6. Lorsque la « charité » domine. La compassion et l’altruisme sont communs à tous les primates. Il est raisonnable de penser que les médecins ne font pas exception. Celui qui clame trop ostensiblement sa compassion est suspect. Très souvent la flamboyance de l’altruisme est proportionnelle au coût des thérapeutiques qui le sous-tendent.
  7. L’argument de l’action. En écho au fléau et à la compassion, le fameux « nous devons absolument faire quelque-chose » est une démagogie qui élimine, a priori et sans preuve, la possible supériorité de l’abstention.
  8. Lorsque l’article comporte des attaques ad hominem, comme accuser les adversaires du médicament d’être des intégristes ou des ayatollahs. On peut être intègre sans être intégriste.
  9. Lorsque la démonstration moléculaire est théoriquement trop parfaite. Le réductionnisme ne fonctionne pas pour les pathologies multifactorielles. Il faut attendre les résultats sur la quantité-qualité de vie. Production de recherche et production de santé ne sont pas synonymes.
  10. Enfin il faut déchirer tout article vantant une pharmacologie préventive dans les domaines où il est évident que seule la prévention hygiéno-diététique est efficace. Ce sont hélas les plus nombreux.

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Does a prediabetic condition increase the risk of developing (type 2) diabetes ?

Development of type 2 diabetes mellitus in people with intermediate hyperglycaemia (‘prediabetes’)

A war on “prediabetes” has created millions of new patients and a tempting opportunity for pharma. But how real is the condition, and is it good medicine?

2018 Study Abstract

Review question
We wanted to find out whether raised blood sugar (‘prediabetes’) increases the risk of developing type 2 diabetes and how many of these people return to having normal blood sugar levels (normoglycaemia). We also investigated the difference in type 2 diabetes development in people with prediabetes compared to people with normoglycaemia.

Background
Type 2 diabetes is often diagnosed by blood sugar measurements like fasting blood glucose or glucose measurements after an oral glucose tolerance test (drinking 75 g of glucose on an empty stomach) or by measuring glycosylated haemoglobin A1c (HbA1c), a long-term marker of blood glucose levels. Type 2 diabetes can have bad effects on health in the long term (diabetic complications), like severe eye or kidney disease or diabetic feet, eventually resulting in foot ulcers.

Raised blood glucose levels (hyperglycaemia), which are above normal ranges but below the limit of diagnosing type 2 diabetes, indicate prediabetes, or intermediate hyperglycaemia. The way prediabetes is defined has important effects on public health because some physicians treat people with prediabetes with medications that can be harmful. For example, reducing the threshold for defining impaired fasting glucose (after an overnight fast) from 6.1 mmol/L or 110 mg/dL to 5.6 mmol/L or 100 mg/dL, as done by the American Diabetes Association (ADA), dramatically increased the number of people diagnosed with prediabetes worldwide.

Study characteristics
We searched for observational studies (studies where no intervention takes place but people are observed over prolonged periods of time) that investigated how many people with prediabetes at the beginning of the study developed type 2 diabetes. We also evaluated studies comparing people with prediabetes to people with normoglycaemia. Prediabetes was defined by different blood glucose measurements.

We found 103 studies, monitoring people over 1 to 24 years. More than 250,000 participants began the studies. In 41 studies the participants were of Australian, European or North American origin, in 7 studies participants were primarily of Latin American origin and in 50 studies participants were of Asian or Middle Eastern origin. Three studies had American Indians as participants, and one study each invited people from Mauritius and Nauru. Six studies included children, adolescents or both as participants.

This evidence is up to date as of 26 February 2018.

Key results
Generally, the development of new type 2 diabetes (diabetes incidence) in people with prediabetes increased over time. However, many participants also reverted from prediabetes back to normal blood glucose levels. Compared to people with normoglycaemia, those with prediabetes (any definition) showed an increased risk of developing type 2 diabetes, but results showed wide differences and depended on how prediabetes was measured. There were no clear differences with regard to several regions in the world or different populations. Because people with prediabetes may develop diabetes but may also change back to normoglycaemia almost any time, doctors should be careful about treating prediabetes because we are not sure whether this will result in more benefit than harm, especially when done on a global scale affecting many people worldwide.

Certainty of the evidence
The certainty of the evidence for overall prognosis was moderate because results varied widely. The certainty of evidence for studies comparing prediabetic with normoglycaemic people was low because the results were not precise and varied widely. In our included observational studies the researchers often did not investigate well enough whether factors like physical inactivity, age or increased body weight also influenced the development of type 2 diabetes, thus making the relationship between prediabetes and the development of type 2 diabetes less clear.

Authors’ conclusions:
Overall prognosis of people with IH worsened over time. T2DM cumulative incidence generally increased over the course of follow-up but varied with IH definition. Regression from IH to normoglycaemia decreased over time but was observed even after 11 years of follow-up. The risk of developing T2DM when comparing IH with normoglycaemia at baseline varied by IH definition. Taking into consideration the uncertainty of the available evidence, as well as the fluctuating stages of normoglycaemia, IH and T2DM, which may transition from one stage to another in both directions even after years of follow-up, practitioners should be careful about the potential implications of any active intervention for people ‘diagnosed’ with IH.

To be prediabetic : a (very) questionable condition

A third of Americans are considered prediabetic – but many may be better off without treatment

A war on “prediabetes” has created millions of new patients and a tempting opportunity for pharma. But how real is the condition, and is it good medicine?

“Practitioners should be careful about the potential implications of any active intervention for people ‘diagnosed’ with intermediate hyperglycaemia (‘prediabetes’)” cochrane.

Prescribed Drug Spending in Canada, 2018

Canada’s love affair with prescription meds…

Drug spending is increasing more than the other major areas of health spending — with a large proportion of drug spending going toward high-cost drugs for a small number of individuals.

Key findings

  • In 2018, $14.4 billion (42.7%) of prescribed drug spending will be financed by the public sector.
  • About 1 in 4 Canadians received a benefit from a public drug program in 2017. Individuals living in low-income and rural/remote neighbourhoods were more likely to receive a benefit.
  • Canadians with drug costs of $10,000 or more represented 2% of beneficiaries but accounted for more than one-third of public drug spending in 2017.

More Information

In 2017 : $40 Billion

Take an in-depth look at prescribed drug spending in Canada and learn more about how different drug classes contribute to current trends in total public drug spending.

In 2013 : $29.3 Billion

Prescribed Drug Spending in Canada 2012 cover image
Canada’s love affair with prescription meds…

Millions of Canadians buy prescription drugs; we spent a record $30 billion in 2013. But the annual rate of growth that year —2.3%— was one of the lowest in more than two decades. This is due in part to an increase in the use of less-expensive generic drugs as well as government policies that help keep prices low. ”

Key findings
  • More than 40% of prescribed drug spending was paid for by the public sector, totalling more than $12 billion. In the public sector, payers include provincial and federal drug programs and social security funds (such as workers’ compensation boards).
  • Generic drugs account for almost three-quarters of use but less than half of spending in public drug programs.
  • The number of Canadians who are taking more than $10,000 worth of prescription drugs every year is on the rise, because public drug programs are spending more on high-cost drugs.
  • In 2012, high-cost beneficiaries accounted for about 25% of public drug spending, compared with only 15% in 2007.
  • Almost half of these people were taking a high-cost drug used to treat conditions such as rheumatoid arthritis, Crohn’s disease and macular degeneration.
Sources

Pharma industry marketing linked to increased prescribing and elevated mortality

Association of Pharmaceutical Industry Marketing of Opioid Products With Mortality From Opioid-Related Overdoses

The new study concluded that drug companies’ marketing of opioids to physicians was “associated with increased opioid prescribing and, subsequently, with elevated mortality from overdoses.”

Read Opioid crisis shows partnering with industry can be bad for public health, theconversation, March 6, 2019.

2019 Study Key Points

Question
To what extent is pharmaceutical industry marketing of opioids to physicians associated with subsequent mortality from prescription opioid overdoses?

Findings
In this population-based, cross-sectional study, $39.7 million in opioid marketing was targeted to 67 507 physicians across 2208 US counties between August 1, 2013, and December 31, 2015. Increased county-level opioid marketing was associated with elevated overdose mortality 1 year later, an association mediated by opioid prescribing rates; per capita, the number of marketing interactions with physicians demonstrated a stronger association with mortality than the dollar value of marketing.

Meaning
The potential role of pharmaceutical industry marketing in contributing to opioid prescribing and mortality from overdoses merits ongoing examination.

Abstract

Importance
Prescription opioids are involved in 40% of all deaths from opioid overdose in the United States and are commonly the first opioids encountered by individuals with opioid use disorder. It is unclear whether the pharmaceutical industry marketing of opioids to physicians is associated with mortality from overdoses.

Objective
To identify the association between direct-to-physician marketing of opioid products by pharmaceutical companies and mortality from prescription opioid overdoses across US counties.

Design, Setting, and Participants
This population-based, county-level analysis of industry marketing information used data from the Centers for Medicare & Medicaid Services Open Payments database linked with data from the Centers for Disease Control and Prevention on opioid prescribing and mortality from overdoses. All US counties were included, with data on overdoses from August 1, 2014, to December 31, 2016, linked to marketing data from August 1, 2013, to December 31, 2015, using a 1-year lag. Statistical analyses were conducted between February 1 and June 1, 2018.

Main Outcomes and Measures
County-level mortality from prescription opioid overdoses, total cost of marketing of opioid products to physicians, number of marketing interactions, opioid prescribing rates, and sociodemographic factors.

Results
Between August 1, 2013, and December 31, 2015, there were 434 754 payments totaling $39.7 million in nonresearch-based opioid marketing distributed to 67 507 physicians across 2208 US counties. After adjustment for county-level sociodemographic factors, mortality from opioid overdoses increased with each 1-SD increase in marketing value in dollars per capita (adjusted relative risk, 1.09; 95% CI, 1.05-1.12), number of payments to physicians per capita (adjusted relative risk, 1.18; 95% CI, 1.14-1.21, and number of physicians receiving marketing per capita (adjusted relative risk, 1.12; 95% CI, 1.08-1.16). Opioid prescribing rates also increased with marketing and partially mediated the association between marketing and mortality.

Conclusions and Relevance
In this study, across US counties, marketing of opioid products to physicians was associated with increased opioid prescribing and, subsequently, with elevated mortality from overdoses. Amid a national opioid overdose crisis, reexamining the influence of the pharmaceutical industry may be warranted.

Les liens entre les industries agroalimentaire et pharmaceutique

Interview de Vandana Shiva, Brut, Février 2019

Selon Vandana Shiva, des multinationales s’enrichissent en vendant des médicaments pour soigner des maladies qu’elles ont elles-mêmes provoquées.

L’écologiste Vandana Shiva dénonce le “cartel du poison”, Brut, Février 2019.

Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology

Doctor payments drove scripts for cancer drugs from Pfizer, Novartis and more: study

New study showed that physicians who received payments over three consecutive years and tied to a specific drug boosted their prescriptions of that product.

Abstract

Background
Financial relationships between physicians and the pharmaceutical industry are common, but factors that may determine whether such relationships result in physician practice changes are unknown.

Materials and Methods
We evaluated physician use of orally administered cancer drugs for four cancers: prostate (abiraterone, enzalutamide), renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (afatinib, erlotinib), and chronic myeloid leukemia (CML; dasatinib, imatinib, nilotinib). Separate physician cohorts were defined for each cancer type by prescribing history. The primary exposure was the number of calendar years during 2013–2015 in which a physician received payments from the manufacturer of one of the studied drugs; the outcome was relative prescribing of that drug in 2015, compared with the other drugs for that cancer. We evaluated whether practice setting at a National Cancer Institute (NCI)‐designated Comprehensive Cancer Center, receipt of payments for purposes other than education or research (compensation payments), maximum annual dollar value received, and institutional conflict‐of‐interest policies were associated with the strength of the payment‐prescribing association. We used modified Poisson regression to control confounding by other physician characteristics.

Results
Physicians who received payments for a drug in all 3 years had increased prescribing of that drug (compared with 0 years), for renal cell (relative risk [RR] 1.81, 95% confidence interval [CI] 1.58–2.07), CML (RR 1.22, 95% CI 1.08–1.39), and lung (RR 1.69, 95% CI 1.58–1.82), but not prostate (RR 0.97, 95% CI 0.93–1.02). Physicians who received compensation payments or >$100 annually had increased prescribing compared with those who did not, but NCI setting and institutional conflict‐of‐interest policies were not consistently associated with the direction of prescribing change.

Conclusion
The association between industry payments and cancer drug prescribing was greatest among physicians who received payments consistently (within each calendar year). Receipt of payments for compensation purposes, such as for consulting or travel, and higher dollar value of payments were also associated with increased prescribing.

Implications for Practice
Financial payments from pharmaceutical companies are common among oncologists. It is known from prior work that oncologists tend to prescribe more of the drugs made by companies that have given them money. By combining records of industry gifts with prescribing records, this study identifies the consistency of payments over time, the dollar value of payments, and payments for compensation as factors that may strengthen the association between receiving payments and increased prescribing of that company’s drug.

Press release.

Big pharma partnering with influencers to sell drugs, medical devices

The latest Instagram influencer frontier? Medical promotions

Abstracts

“By enlisting influencers to market their health care products amid a stream of Facetuned photos, pharmaceutical and biotechnology companies co-opt narratives that give social media users a sense of how healthy they can be, if only they had this product.”

“Social media enables its users to connect over shared interests, locations, and even illnesses. Using this formula, health care companies locate potential influencers who can use these commonalities to reach and build trust with an audience.”

“One wonders why a company would assume the risk of misinformed patients, as they are responsible for what their paid endorsers say. The reason is simple: One in three consumers in the US consult social media for health-related matters. “

Read The latest Instagram influencer frontier? Medical promotions, on vox, Feb 15, 2019.

La façon de penser de l’industrie pharmaceutique

Considérons enfin les phases de vie

Publié par Luc Perino, médecin généraliste, humeur du 01/01/2019

La cigale Magicicada septemdecim est ainsi nommée car elle a une phase larvaire de dix-sept ans suivie d’une phase adulte (imago) de seulement six semaines. Il nous est difficile d’imaginer qu’un état larvaire constitue l’essentiel d’une durée de vie.

La notion de « phase de vie » est capitale dans la compréhension du vivant. La phase adulte de cette cigale ne sert qu’à la reproduction. En termes d’évolution, il est superflu de vivre après avoir produit une progéniture capable d’atteindra elle-même l’âge de la reproduction.

Les médecins n’ont pas été formés à réfléchir en ces termes de phase de vie. L’idée de soigner les nourrissons et les enfants est relativement récente, la mortalité infantile a longtemps été vécue comme une fatalité. Aujourd’hui, la médecine consacre l’essentiel de son budget à la prolongation de la vie adulte et l’essentiel de sa communication à en promouvoir le programme.

La santé publique pourrait pourtant profiter d’une médecine mieux formée aux phases de vie. Cette individualisation du soin serait assurément plus pertinente de celle dont les marchands de santé ont récemment fait un slogan. Identifier l’ADN tumoral chez un adulte est un leurre d’individualisation et un piètre progrès conceptuel en cancérologie.

L’immense majorité des essais cliniques en pharmacologie est réalisée sur des adultes. Les résultats en sont généralement extrapolés aux enfants et aux vieillards par de simples règles de trois, basées sur le poids ou la fonction rénale. Médicaments parfois utilisés chez la femme enceinte, alors que la physiologie et l’immunologie d’une grossesse, d’un embryon ou d’un fœtus sont peu comparables à celles d’un adulte.

Les ressources métaboliques d’un enfant sont allouées à la croissance, celles d’un adolescent à la maturation sociale et sexuelle, celles des adultes à d’incessants compromis entre reproduction, soins parentaux et gestion de la complexité socio-culturelle ; celles des séniors sont allouées exclusivement aux processus de réparation. Tous ces individus ont des physiologies aussi différentes que le sont celles de la larve et de l’imago de notre cigale.

Plus trivialement, une hypercholestérolémie ou une hypertension n’ont pas la même nocivité à 20 ans et à 70 ans. Une cellule cancéreuse n’a pas le même destin à 10, 40 ou 70 ans. Une douleur articulaire n’a pas la même valeur sémiologique à 5 ans qu’à 20 ou 80 ans. Un déficit cognitif passager n’est pas le même motif d’alerte à 15 ans qu’à 75 ans. Aucune chimie ne convient aux embryons, aucun psychotrope ne convient aux enfants, la morphine ne convient pas aux adultes, la prévention immunitaire n’est pas adaptée aux vieillards.

Depuis un demi-siècle, nos universités médicales se font méthodiquement enfermer dans la façon de penser de l’industrie pharmaceutique. Revenir à plus de biologie fondamentale et mieux enseigner les phases de vie permettrait de se libérer de ce carcan cognitif.

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