Category: Opinion column

ANNETTE LEXA , PhD in Toxicology

MARCH 8, 2016 

A priori, if we believe official messages communicated through the national cancer plan 2014-2019 (1) , we are witnessing real progress in the domain of anti-cancer therapies, and society (via patient associations) is ready to make it possible for everyone - in the name of the sacrosanct "equality of opportunity" - to have access to the best treatments, especially experimental ones. Otherwise, society and patient associations will even consider that this would be a "loss of opportunity".

Faced with the boom in oral chemotherapy, the 2014-2019 national cancer plan - which is silent on the origin of this boom - gives great importance (much more than to prevention) to improving "compliance (adherence to treatment) and management of adverse events" of new "innovative" anti-cancer therapies.

The term "compliance" (page 16 of the report) is scary and says a lot about the managerial necessity to make them accepted at all costs to the body and psyche of reticent patients by "securing" their care "pathway".

For the past 10-15 years, we have been witnessing an almost frenetic rush to bring new anti-cancer molecules to market. At the same time, the price of these new molecules is exploding. Patients are almost constrained to be enrolled in therapeutic trials.

What patients don't know is that there is no correlation between price, cost to market and efficacy in terms of survival rates. Moreover, these new molecules are not subject to rigorous clinical trials or to the search for proof of efficacy. Their efficacy - if it exists - is purely statistical and it is the standardization of treatments that prevails by type of cancer and not by type of patient. A careful reading of the scientific articles published on this subject in recent years even suggests that it is more important to put them on the market than to ensure their effectiveness and safety (3).

These drugs benefit from a fast-track marketing procedure. However, it has been proven that these drugs placed on the market prematurely have more serious adverse effects than those placed on the market more rigorously. Worse, once a molecule is placed on the market (such as bevacizumab), it is difficult to withdraw it from the market.

In the United States, of the 71 compounds approved by the FDA (Food and Drug Administration) between 2002 and 2014, the improvement in survival for all cancers combined is 2 months (5). For solid tumors, a review by the EMA (European Medicines Agency) shows an improvement of 1.5 months (3).

Currently, in Europe and in the USA, the regulatory agencies accept non-randomized trials, trials without controls, biased protocols, phase III trials when phase II was not convincing and they turn a blind eye to the quality of publications of these trials.
Worse, they accept as proof of "efficacy" new "innovative" molecules, "surrogate end points", measurements of biochemical sub-parameters, which are less costly to implement and which replace the only criterion that should prevail in oncology, survival, as a criterion of efficacy. It doesn't matter if you die in 10 days, the oncologist will look with satisfaction at your biomarkers rising.

The sky is getting a little darker when we learn (9) that a serious setback is announced in the new health law in the USA (21st Century Cures Act) whose stated objective is to make the best possible return on investment by reducing the time and number of patients in clinical trials, or even to abolish all clinical trials and replace them with "surrogate end points" (biochemical sub-parameters), in vitro and in silico studies. The USA is paving the way for a regression that is all the more serious since currently, in the USA, one third of drugs are approved after trials lasting less than 6 months and the average number of patients is 760. Underhanded negotiations around the future transatlantic treaty make this scenario increasingly likely as far as we are concerned.

In the USA, a number of oncology experts even believe that the moral red line between reasonable profits and profits has been crossed (3, 6). Partly because the poorest cannot afford to pay, as they no longer have medical insurance (a cancer treatment costs the insured about 20,000 to 30,000 dollars).

In France, costs are the same but we don't realize it because we are all covered by health insurance and optimal reimbursement.

In terms of "fight against cancer", it is also important to remember that 85% of the research is public and therefore financed by taxpayers and donations, the oligopolistic market (which relates to the oligopoly, a market characterized by a small number of sellers against a large number of buyers) of these pharmaceutical companies spending only 1.5% of its revenues on this research, between 5 to 13% on clinical trials and between 20 to 45% on marketing.

After this little clarification, we have a very different reading of the latest 2014-2019 cancer plan: the explosion of patient recruitment in early phase clinical trials of "innovative" drugs (do they really have a choice?), the public financial participation in this forced march, which is duly praised, leaves a strange bitter taste: is it the health of patients or the market that takes precedence? Not only are patients being lied to, but it is seriously damaging to both patients and research. For their safety alone, patients and physicians must demand greater rigour. Balanced health care budgets are also at stake.

Finally, it is questionable whether health agencies are serving the interests of patients or laboratories: in light of the appointment of Professor Agnès Buzyn as head of the Haute Autorité de Santé, it is reasonable to wonder (7, 8). Health agencies should regain their primary vocation, which is to ensure the protection of the public, and they should provide clear and transparent information to the public.

REFERENCES 

1. Plan Cancer 2014-2019 , LE RAPPORT AU PRÉSIDENT DE LA RÉPUBLIQUE , Février 2016

2. Au nom de tous les seins, documentaire France 5

3. Light D.W., Lexchin J., Editorials, Why do cancer drugs get such an easy ride? Rushed approvals result in a poor deal for both patients and cancer research , BMJ 2015;350:h2068

4. Prasad V et coll., The Strength of Association Between Surrogate End Points and Survival in Oncology: A Systematic Review of Trial-Level Meta-analyses. JAMA Intern Med. 2015 Aug;175(8):1389-98

5.Fojo T, Mailankody S, Lo A. Unintended consequences of expensive cancer therapeutics

- the pursuit of marginal indications and a me-too mentality that stifles innovation and

creativity, JAMA Otolaryngol Head Neck Surg 2014;140:1225-36.

6. Hagop Kantarjian et coll., High Cancer Drug Prices in the United States: Reasons and Proposed Solutions J Oncol Pract 2014 Jul 6;10(4):e208-11.

7. Les petits arrangements de la nouvelle présidente de la Haute autorité de santé (7 mars 2016) https://www.mediapart.fr/journal/france/070316/les-petits-arrangements-de-la-nouvelle-presidente-de-la-haute-autorite-de-sante

8. Le professeur Agnès Buzyn nommée Directeur de la HAS. La victoire de big onco (8 mars 2016) http://docteurdu16.blogspot.fr/2016/03/le-professeur-agnes-buzyn-nommee.html 9. Avorn J and Kesselheim A.S., The 21st Century Cures Act — Will It Take Us Back in Time? N Engl J Med 2015; 372:2473-2475

Cécile Bour, MD, May 14, 2020

In the era of EBM (proof-based medicine), the headlines of last few weeks during the Covid 19 pandemic have highlighted the drifts that undermine this approach of a modern medicine.

We should not only blame the recent context; over the last decade and perhaps more, there are three main problems in modern medicine that Jeanne Lenzer, an investigative medical journalist, and Shannon Brownlee, Vice President of the Lown Institute, « a nonpartisan think tank advocating bold ideas for a just and caring system for health in the United States », have denounced in "Issues" column of their site.

These three drifts seriously weaken evidence-based medicine and jeopardize the benefits owed to patients, and they are currently exacerbated in this period of crisis.

Three main drifts of today's medicine

• The main drugstore in the city where I practice has the motto "primum non nocere" above the counters. But, according to Lenzer and Brownlee, doctors are insufficiently trained to discern good science from poor studies, and prefer to use molecules they know and whose effect appears biologically plausible. Fear and haste have sounded the death knell for the Hippocratic maxim, a pillar of medicine. Beliefs and unproven faith in medications used for other medical conditions have been considered, without concern for their real usefulness against an emerging and unknown virus, or their possible harmfulness.
• The second pitfall identified by the authors is the prominent role of the media today. On the one hand,  convictions and opinions of non-physicians are following in the footsteps of politicians, to whom the floor is widely and generously given. On the other hand, many of media that echo this are ignorant and incompetent in scientific method or in search for evidence, and also have a commercial interest in hype around these well-known and popular, but null, town criers.

We can only agree with this observation, having ourselves been confronted with a very unpleasant episode of attacks from a TV host, who mediated his experience of prostate cancer at will to convince people who asked him nothing, to undergo prostate screening test, in spite of all the non-recommendations of such screening [1].
The naive crowds that "follow" these characters, fan clubs generally very well supported on social networks, do not facilitate the expression of cautious doctors or independent collectives like ours, which are inevitably a killjoy in the general hope. The word of the Cassandras is hardly a media-friendly one...

●The third calamity denounced by Lenzer and Brownlee concerns poor quality studies that do not include what is called a "control arm", i.e. inclusion in the study of a comparison group that has not been given the drug being tested. The control arm is the cornerstone of a strong randomized controlled trial. It aims to formally establish the true efficacy of a product, highlighting possible biases in the tested protocol. For example, a drug may appear to be effective in reducing the risk of a given disease when the population to which it was administered is already naturally less at risk, because they are younger, healthier or have easy access to medical care. A control arm with a wide range of subjects can show ineffectiveness of the test drug in certain groups of  population and thus point to errors in reasoning or biases that would go unnoticed. In hastily constructed studies, on the other hand, potential harms may be underestimated. 

But even outside of critical health periods, such as in the field of cancer for example, proclamation of "miracle" drugs has been legion in recent years, with questionable studies, selling hope of so-called "revolutionary" chemotherapies. On this subject read the post of Annette Lexa, our toxicologist.

We add to this last point on the poor quality of medical researchn a particular type of study that is currently spreading, it is the "non-inferiority" test, all the more fraudulent and perfidious that nobody understands a drop.

Doshi and all. 2] studied informed consent forms from non-inferiority studies on antibiotics. Their observations are generalizable, however, because there are many applications of this type of study, in diabetes, cardiology, infectiology and cancerology. Doshi et al. found that often neither the methodological experts nor the members of personal protection committees were able to define the true objective of the study from the information forms given. For the methodologists, only 1 out of 50 trials, according to them, correctly restituted the objective of the study; for the patients, 7 out of 50 studies succeeded in doing it. These results raise the question of whether consent is truly an informed one, and thus whether the trial is even ethical.

But what are we talking about?

Non-inferiority trials

We have given a summary explanation about the MyPEBS study for personalised breast cancer screening which concerns the theme of our site, a study that we have analyzed in depth here: https://cancer-rose.fr/my-pebs/.

In the non-inferiority trial it is a question of comparing two elements (two medical devices or two procedures, or two drugs) to check whether the device or procedure or treatment being tested would not be worse than what is already in use, accepting a certain loss of effectiveness within a certain tolerated margin, known as the non-inferiority threshold.

It is not a question of verifying whether the system, procedure or drug tested would be superior to former one. This is often how the press reports it and how doctors and public understand it, but it is not the case!

For example, for breast cancer screening, intended purpose is normally to reduce severe forms of cancer. In the MyPEBS non-inferiority study, if the new personalized screening tested does not appear to favor a rate above 25% (arbitrarily set threshold) for additional severe cancers, the trial will be declared a success. You have read correctly. There is no control group there either to test what would happen without screening, which would be legitimate though since recent studies on this screening no longer manage to demonstrate a positive benefit/risk balance.

It is true that in non-inferiority trials in cancerology the control arm is rarely considered, this being judged to be unethical given seriousness of disease, and patient cannot be deprived of any care. But here, in the MyPEBS study, healthy and non-complaining women are being tested, we should remember.

What must therefore be understood, in short, is that it is possible, with non-inferiority trials, that a new health procedure can be accepted as effective, even if its therapeutic or beneficial effect is slightly inferior to current standard. In a non-inferiority trial, the new procedure or drug is not supposed to make the participant healthier than she would have been outside the trial, since superiority of the procedure or drug is not sought.

The only assumptions are :

- In the best configuration, participants randomized into the study's test group could fare as well as if they had not participated in the trial,
-or then potentially worse within an arbitrarily accepted margin, in the wrong scenario.

And everyone is happy. The public because they are not well informed and believe that what was tested on them is 'superior', the journalists who did not grasp the subtleties of the methodology and write laudatory articles, and above all the designers of the study. Why is such an approach necessary? Because with this set-up, the study is subtly biased towards the result desired by the promoter, which is to obtain or safeguard a market share much more than to answer a scientific question whose stake is the well-being of the patient. For MyPEBS, the aim is to establish breast cancer screening, since women will only have a choice between two options: old screening or personalized screening, but screening in all cases.

To caricature, the patient or population will be worse or not less well, but the good news is that the study is a success..

Two interesting articles to help the practitioner in the critical analysis of the studies that published

Vinay Prasad, in an editorial in the JGIM[3] (Journal of General Internal Medicine) where he actually quotes the results of Doshi et al, refers to the publication of Aberegg, Hersh and Samore who analyzed 183 non-inferiority comparisons of 163 clinical trials published in the five major impact medical journals.

Aberegg and colleagues found that only 70% of the non-inferiority studies explicitly stated why new therapy would have an advantage, and in 11% of cases no advantage could be inferred. This suggests to these authors that many of these studies should not have been conducted.

What should the practitioner beware of and what trials of non-inferiority can he trust? According to V.Prasad, it is necessary to :

• Consider whether new therapy is less expensive, more convenient, less invasive or less toxic than old one. If answer is no, stop looking, he says! There must be a positive compensation for the patient for loss of effectiveness of the new procedure or new drug being tested. If not, there is no point in learning about the "novelty".
• Ask yourself how much loss of effectiveness of the new procedure or new treatment you would be willing to accept in order to adhere to it. 5% loss of effect, or 10%? More or less?
• Be concerned about the margin of inferiority accepted. E.g. for MyPEBS the non-inferiority threshold is very generous. This means that if, at the end of the new screening, 25% additional serious cancers are found, the study is "successful". This margin would have to be justified, and this justification would have to appear at least in the study protocol, which is not the case.
• Finally, consider whether the new intervention was in fact 'inferior', not 'non-inferior'.

The French independent journal Prescrire[4] examined  problems of these particular trials in 2006. Their advice is similar to that mentioned above. For the journal, one must be critical of the threshold of non-inferiority that is chosen a priori, arbitrarily by trial designers. For the patient, this threshold is equivalent to the loss that is consented to in relation to the reference treatment or device.  It is therefore necessary to be sure that the result is not in fact a true inferiority.

For Prescrire, in short, these tests are intended to simply exclude the possibility that a treatment or process is massively worse than what already exists. When the treatment or procedure is slightly less effective, and within a certain accepted margin, the new treatment or procedure is only of interest to the patient if it brings other benefits in compensation. And this is where the stick can hurt, as in this study we regularly criticize, and not just us.

To conclude:

The urgency and willingness to obtain results quickly justifies dispensing with well-conducted controlled studies and exposes us, because of flawed and poorly executed studies, to biased medical judgments and erroneous conclusions.

Improper, sometimes excessive, communication by lay people or ignorant media aggravates media coverage of drugs or procedures that we do not know what they actually induce, whether they do more harm than good.

These problems pre-existed before the context of the Covid19 pandemic which only brought them to light.

Research in science is important, yet it must meet quality standards, be done by scientists who are concerned about respecting proven methodologies and meeting standards, and this in a serene media environment.

This is currently not the case, as damage and physical inconveniences to health of populations are aggravated by misinformation and pollution of scientific debate by quarrels of opinion.

If we want to make good science that is useful to people, we must develop a critical spirit, constantly verify results of studies promoted as revolutionary by media, see by which methods conclusions have been reached.

We have come full circle; if we want to make good medicine we will always return to what is proclaimed at the front of the drugstore, the basic principle that must underpin our medical practice: "primum non nocere" .

References

[1] https://cancer-rose.fr/2020/02/06/ah-mais-quelle-aubaine-ce-cancer/

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710221/

[3] EDITORIAL
Non-Inferiority Trials in Medicine: Practice Changing or a Self-Fulfilling Prophecy?

Vinay Prasad, MD, MPH

Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA; Department of Preventive Medicine and Public Health, Oregon Health and Science University, Portland, OR, USA; Center for Health Care Ethics, Oregon Health and Science University, Portland, OR, USA.

J Gen Intern Med 33(1):3–5
DOI: 10.1007/s11606-017-4191-y
© Society of General Internal Medicine 2017

[4] La Revue Prescrire avril 2006/Tome 26 N°271, page 249

Summary by Cécile Bour, MD

September 18, 2020

BMJ: first published as 10.1136/bmj.m3592 on 17 September 2020.
Quote this as: BMJ 2020;370:m3592
Published: 17 September 2020
https://www.bmj.com/content/370/bmj.m3592

Hazel Thornton is a health science researcher at the University of Leicester.

She received her PhD in Science from the University of Leicester for her contributions to medicine and patient care. The award recognizes her work in advocating for patients and changing perceptions within the medical research and health care community.

The BMJ publishes her letter on the subject of patients' informed consent, which is often flouted, even though this is a right and a major ethical issue.

Hazel Thornton refers to a publication by Helen Haskell [1] [2], founder of Mothers Against Medical Errors, which reports the severe criticisms of the "Cumberlege Report" [3] on the British health care system, judged "disjointed, siloed, unresponsive, and defensive”.

The report points to the failure regarding the informed consent of healthy patients, whose non respect is a violation of human rights according to the Declaration of Helsinki [4].

What is of great concern is “the testimony from hundreds of patients reporting lack of informed consent.”

While health care professionals are supposed to work “in partnership with patients to make good clinical decisions," which is at “the heart of good medical practice".

Informed consent and screening

Hazel Thornton writes in her letter to the BMJ:

Asymptomatic people, too, are the target of health professionals in preventive medicine. Medical interventions used in screening are not without potential for harm, so properly informed consent must be sought. Not to do so is an abuse of human rights. Flouting the four basic principles of medical ethics—autonomy, beneficence, non-maleficence, and justice—must not go unchallenged. Incredibly, in the 21st century, blatant disregard for the right to proper consent is still occurring. Two examples clearly illustrate this.

The first is an experiment to determine the effects of manipulating invitation information provided to around 6000 asymptomatic women in the province of Messina, Sicily, “to increase uptake” into their breast cancer screening programme.[5] The second is the UK NHS breast screening programme AgeX trial, which was started in June 2009 and announced as “likely to be the largest randomised controlled trial ever undertaken in the world,” recruiting millions of women. Efforts to challenge this trial, with its flawed consent process, have met with “siloed, unresponsive and defensive” attitudes.[6] [7]

H.Haskell says, "How to change it is still an unsolved problem. There have been inquiries, reports, and recommendations over the years, but the fundamental issues around power, justice, and compassion are still with us. " What can be done to end these blatant abuses of the right to properly informed consent and tackle the lack of engagement ? 

Cancer Rose Reflections

Indeed, we have to draw a parallel with the European MyPEBS clinical trial on personalized breast cancer screening.

We have already reported its multiple shortcomings, which we denounced in a joint letter from 4 groups defending independence and integrity in health, a letter relayed among others in the BMJ.

Participants in this MyPEBS study are provided with a so-called consent brochure. The problem is that it does not comply with the law, which requires that this consent be based on fair, clear, complete and unbiased information.

We have summarized our concerns about the brochure for the MyPEPS study here (see point 3 ): https://cancer-rose.fr/my-pebs/2019/06/13/argument-english/

Over-treatment is not mentioned, with over-diagnosis indicated at its lowest range.

In conclusion, we have the same questions as Hazel Thornton:

After the French scientific and citizen consultation, which demands fair and complete information [8], how many laws, declarations, reports and investigations should we hope for in order to obtain the fundamental right to information and informed consent for the patient, and a firm and solid commitment from health authorities and governments to guarantee this right to the patient?

Références

References

[1] https://pubmed.ncbi.nlm.nih.gov/32763955/

[2] https://patientsafetymovement.org/advocacy/patients-and-families/patient-advocates/helen-haskell/Founder of Mothers Against Medical Error

[3] Haskell H. Cumberlege review exposes stubborn and dangerous flaws in healthcare. BMJ 2020;370:m3099.
doi: 10.1136/bmj.m3099 pmid: 32763955

[4] World Medical Association. Declaration of Helsinki. https://www.wma.net/fr/policies-post/declaration-dhelsinki-de-lamm-principes-ethiques-applicables-a-la-recherche-medicale-impliquant-des-etres-humains/

5] Italian study on the manipulation of women, we talk about it here :https://cancer-rose.fr/en/2020/12/17/manipulation-of-information/

[6] Bewley S, Blennerhassett M, Payne M. Cost of extending the NHS breast screening age range in England. BMJ 2019;365:l1293.
doi: 10.1136/bmj.l1293 pmid: 30971394

[7]We were talking about this trial

here : https://cancer-rose.fr/en/2020/12/29/cost-of-extending-the-nhs-breast-screening-age-range-in-england/ and here: https://cancer-rose.fr/en/2020/11/30/the-largest-clinical-trial-in-great-britain-on-breast-cancer-screening-was-halted/

[8] https://cancer-rose.fr/en/2020/12/30/citizen-and-scientific-consultation-on-breast-cancer-screening-in-france-steering-committee-report/

See at the end of the article the summary of the citizens' requests in red, first point being related to the quality of information

By Cancer Rose

1 December 2020

The fact that eating habits have an influence on the risk of developing cancer, and that the incidence of cancer among vegetarians in particular is lower than among people having a meat diet, has already been the subject of scientific studies [1].

A more recent publication [2] than the above-mentioned one, analyzing 86 cross-sectional studies and 10 prospective cohort studies, reports a significant protective effect of a vegetarian diet on the incidence and mortality of ischemic heart disease (-25%), and on overall cancer incidence (-8%). The vegetarian diet was found to significantly reduce the overall risk (-15%) of developing cancer.

But a post by the physician essayist and novelist, Dr. Luc Perino, whose articles [3] we often relay, testifies to another aspect of the behavior of vegetarians and vegans that could have an effect on the reduced incidence of cancer among this group of people, namely the lower participation in screening.

Non-carcinogenic diet and participation in screening / opinion column by Luc Perino

We publish here, with the kind permission of Dr. Perino, the post that you can read, among many others, on the author's blog [4]:

There is no longer need to conduct studies in order to prove that lower meat consumption reduces the incidence of cardiovascular disease. The subject is no longer under debate since half a century. Decreased meat consumption and physical exercise have contributed to the new gains in life expectancy observed in recent decades. 

We also know that low-meat diets reduce the risk of colon cancer. In recent years, the large number of vegetarians has made it possible to carry out studies of greater statistical value on the effects of such diets on health. The question of cancers has obviously been addressed and it appears that in addition to colon cancer, the vegetarian diet also reduces cancers as unexpected like breast and prostate cancer. Generally speaking, all cancer risks are reduced to a greater or lesser extent.

Confounding factors such as tobacco have obviously been taken into account, and some studies went so far as to consider other confounding factors such as personality traits and other elements of a reasonable vegetarian lifestyle (excluding fanatical vegans). For example, vegetarian women take fewer hormone treatments during menopause and further reduce their risk of breast cancer.

The funny thing, if I dare to phrase it this way, is that vegetarians participate much less in organized cancer screening programs. Some will conclude that they are carriers of unknown cancers that will develop sooner or later. This hasty conclusion, somewhat tainted by pro-screening ideology, is contradicted by lower overall cancer mortality among vegetarians of all ages who are followed for a long time.

This is explained by the fact that many of the cancers detected are either false positives or cancers that would never have had a clinical manifestation before death from another cause.

Vegetarians therefore have fewer clinical cancers, fewer detected cancers and fewer virtual or sub-clinical cancers. The health benefit of this triple protection is even greater than that already observed in the reduction of mortality. Indeed, the anxiety associated with all screening and the biographical stigma associated with a cancer diagnosis aggravates morbidity and mortality. We know that all cancers, whether clinical, screened or virtual, have the same psychological and biographical repercussions.

We will not go so far as to encourage vegetarians in their diagnostic recklessness, as this could shock the academy. Nevertheless, we must congratulate them for their sanitary perspicacity and their serenity in the face of pathological destiny, without forgetting to praise their climatic altruism.

Study on participation in screening

In the bibliography of this post, cited by the author, we find a study published in the BMJ in 2017 on health behaviors according to population groups following specific diets [5].

31,260 participants were studied from four diet groups (18,155 meat eaters, 5,012 fish eaters, 7,179 vegetarians, 914 vegans) in the British EPIC-Oxford cohort [6]. 

Compared to meat eaters, vegetarian and vegan women reported lower participation in breast cancer screening, and vegetarian men were less likely to undergo PSA testing for prostate cancer. 

No difference was observed in women for cervical cancer screening. 

For women in all non-meat eating groups there was also a lower consumption of hormone replacement therapy for menopause compared to meat eaters. 

Less use was observed for any kind of medication in general among participants in all no-meat groups. 

Conclusion

Behavioral differences, rather in the sense of lower participation in breast cancer screening, prostate cancer screening, lower hormone replacement therapy and overall drug use were observed in the non-meat diet groups. Apparently these population groups are thus less exposed to the risk of developing cancers, less exposed to clinical cancers (revealed by symptoms), and to sub-clinical cancers (not symptomatic), whose over-detection unbridled by mass screening feeds over-diagnosis, and all this in a context of less anxiety, less morbidity and less premature mortality among vegetarians, observed even in the long term, probably in relation to a healthier general life behavior, and not only due to vegetarianism alone [7].

References

[1] https://academic.oup.com/ajcn/article/89/5/1620S/4596951?searchresult=1

[2] https://pubmed.ncbi.nlm.nih.gov/26853923/

[3] https://cancer-rose.fr/2017/07/04/les-billets-de-luc-perino/

[4] https://lucperino.com/715/vegetariens-et-cancers.html

[5] https://bmjopen.bmj.com/content/7/12/e018245

[6] The Oxford Component of the European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort of 65,000 men and women living in the UK, many of whom are vegetarians.

[7] https://theconversation.com/les-vegetariens-vivent-ils-plus-longtemps-probablement-mais-pas-parce-quils-sont-vegetariens-72929

Cécile Bour MD, 15 June 2020

The question was asked by Quebec scientists in the newspaper Le Devoir.
https://www.ledevoir.com/opinion/idees/580791/et-si-la-covid-19-vous-avait-sauve-e

Not everyone benefits from screening, especially if it is a screening whose risk-benefit balance is increasingly questioned in view of the cumulative risks, and in view of the benefit that is less and less proven with the hindsight we now have on breast cancer screening campaigns.
This pause in screening could be an opportunity for research, to reflect on information for women without alarmism or threats towards them, to ask the right questions about the use of financial resources in health care towards procedures and tools that are proven beneficial to populations, as the Quebec signatories conclude:
"The current context must be used to question more broadly our choices in the offer of clinical services in order to prioritize interventions that have demonstrated effectiveness and concrete benefits for patients.”

Read also the analysis of :
-Welsch/Prasad https://edition.cnn.com/2020/05/27/opinions/unexpected-side-effect-less-medical-care-covid-19-welch-prasad/index.html
-Judith Garber https://lowninstitute.org/reduced-cancer-screenings-in-covid-19/
-Susan Bewley https://blogs.bmj.com/bmj/2020/04/14/susan-bewley-things-should-never-be-the-same-again-in-the-screening-world/
-John Horgan https://blogs.scientificamerican.com/cross-check/the-cancer-industry-hype-vs-reality/

Article by Judith Garber, May 9, 2020
https://lowninstitute.org/reduced-cancer-screenings-in-covid-19/
Abstract Dr. Cécile Bour MD

Judith Garber is a scientist in political science and health policy at the Lown Institute. (The Lown Institute based in Massachusetts, United States, is a non-profit organization, a "non-partisan think tank that advocates innovative ideas for a fair and caring health system").
Screening procedures and routine medical visits have declined since the Covid-19 pandemic. According to the author, this trend is not necessarily deleterious, as there will likely be a decrease in unnecessary and harmful care.

A recent analysis conducted by the EPIC* Health Research Network used electronic health record data from 2.7 million patients in the U.S. and compared the rates of cervical, breast and colon cancer in the pre-Covid period with the current Covid period. They found that screening appointments in March 2020 decreased by 86-94% compared to the average number of screening appointments that occurred monthly from January 1, 2017 through January 19, 2020.
*EPIC: The Epic Community is a global community of healthcare organizations.

What effect would this drastic decrease in screening have on patient health? The authors of the EPIC report claim that it will be disastrous….
But is this grim prediction likely? According to J.Garber, several points need to be considered.

Mortality by disease vs. all-cause mortality

Although there is some evidence that cancer screening can reduce specific mortality, i.e. mortality from specific cancers, there is much less evidence of benefit on all-cause mortality (the risk of dying overall).

Editor's note: In the above cited study, the effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. 
( Note that the interest in all-cause mortality is that it includes both mortality from the disease and mortality from treatment of the disease.
If there is an impact with decreased all-cause mortality, it means that screening (and treatment) are effective. The overall mortality thus serves as a warning signal; e.g., if there is an abnormal offset between overall and disease-specific mortality, this should raise the question of whether an adverse effect of screening may have been insufficiently taken into account. Overall mortality is not generally used as a judgement criterion, which is regrettable because it implies a loss of information. Editor's note)

In 12 randomized screening trials, reviewed by Dr. Vinay Prasad and colleagues in an article published in the BMJ, seven failed to show a decrease in overall mortality, despite lower rate of disease-specific mortality. In some cases, overall mortality in the screening group was therefore higher than in the non-screened group. What is the reason for this?
The possible explanation is that the negative effects of screening, in these cases, may counteract the benefits. While cancer screening reduces mortality for some cancers, for others it leads to many more false positives with unnecessary biopsies, as well as over-diagnosis and over-treatment. Thus unnecessary surgery and complications of diagnostic and therapeutic tests and procedures have a negative effect on health in screened groups. See also [1].
The authors of the EPIC report should therefore have included in their alarming conclusion not only potential cancer deaths due to lack of screening, but also potential false positives and cascade of events avoided (over-diagnosis followed by over-treatment), and should also have taken into account the lack of evidence regarding the overall benefits of screening on overall mortality.

Not everyone benefits from screening

Not everyone is equally likely to benefit from cancer screening explains J.Garber. The likelihood of a young adult developing cancer is very low, making them more likely to be exposed to screening damage than actually helped.

At the same time, at a very advanced age, cancer screening also becomes less beneficial because older people no longer have the life expectancy to benefit from screening, but on the other hand are more susceptible to the harmful complications of testing and treatment that result from the detections. For example, the US Preventive Services Task Force (an independent US agency that reviews health devices) recommends colorectal cancer screening only between the ages of 50 and 75.

Yet many people are being screened for cancer outside the recommended ages, even though they are unlikely to benefit from it, the author explains.
In one 2014 study published in JAMA, among elderly patients with a very high mortality risk , 37.5% were screened for breast cancer, 30% were screened for cervical cancer and 40% were screened for colorectal cancer. Among women who had previously undergone a hysterectomy but did not have cancer, 34% to 56% still had been screened for cervical cancer within past three years.
Although cervical cancer screening is not recommended for young women aged 15 to 20, an estimated 1.6 million Pap tests (smears) are performed unnecessarily on women in this age group each year.
In the EPIC Network's analysis above, these are not considered. If most of the people who missed out on screening in March 2020 were those at lowest risk, then a reduction in screening participation may not be such a bad thing overall - especially if it was the number of obviously inappropriate screenings that was decreasing.
However, with the information we do have, we do not know which patients have avoided screening, making it impossible to estimate the real number of lives lost or damage reduced in this 'Covid pause' from screening.

An opportunity for research

The authors of the EPIC report explain the issues that seem clear to them, namely the 'lives lost' due to reduced screening. However, it is very likely that this number is overestimated, given the high rates of inappropriate screening in the real world, as well as the potential negative and unaddressed effects of screening on overall mortality.
Although the true impact of the sudden halt in screening due to Covid-19 remains unknown, according to J. Garber we have an opportunity to find out.
Such a drastic change in screening is unusual, so we must take advantage of this unique event and follow the results of this historical experiment to better understand the actual health effects - both beneficial and harmful - of cancer screening.

Editor’s note

A few cautions: this monitoring of data will depend on the evolution of the outbreak and whether or not screening is resumed. Two months of interruption, as is the case in France, may be insufficient to draw these conclusions or to discern real variations in cancer incidence and mortality rates. This can be made even more complicated and the conclusions even more hazardous if the resumption of screening is not carried out in a uniform and homogenous manner in all regions of France, depending on the persistence here and there of Covid clusters that curb the public's willingness to attend the various screenings. Only if the interruption of screening would continue for a few more months, either because of the persistence or resurgence of the outbreak, or because of public resistance (fear of going to the doctor's office or of having to undergo a colonoscopy in the context of an epidemic), the situation would be quite different and results could emerge.

Reference :

1] https://cancer-rose.fr/2019/08/08/synthese-detudes-un-exces-de-mortalite-imputable-aux-traitements-lemportant-sur-le-benefice-du-depistage/

https://blogs.scientificamerican.com/cross-check/the-cancer-industry-hype-vs-reality/

February 12, 2020 Par John Horgan 12 février 2020
John Horgan is a science journalist who manages Stevens Institute of Technology 's Science Writing Center. We are going to try to summarize the key points of his article here. Summary by Cécile Bour, MD

Cancer medicine generates enormous revenues, but marginal benefits for patients.

According to the author, there is a huge gap between the sad reality of cancer medicine in the United States and the optimistic claims made by the cancer industry and its media catalysts.
Cancer has spawned a huge industrial complex, including government agencies, pharmaceutical and biomedical companies, hospitals and clinics, universities, professional societies, non-profit foundations and the media.
Cancer-industry boosters claim that research, screening and treatment investments have led to "incredible progress" and millions of "cancer deaths averted," as claimed on the American Cancer Society's home page, a non-profit organization that receives money from biomedical companies.
Cancer experts and the media often describe new treatments with laudatory terms such as "medical breakthrough," "revolutionary," "miraculous," ("innovative," often heard in France, Editor’s note).
Cancer centers “frequently promote cancer therapy with emotional appeals that evoke hope and fear while rarely providing information about risks, benefits, costs, or insurance availability.” (as in the French Cancer League and the numerous cancer institutes, Editor’s note). These highlighted therapeutic achievements concern particular forms or rare cancers, which, according to the author, are exceptional in the midst of a "litany of failures".

Mortality rate

The best way to measure progress against cancer is to look at mortality rates, the number of people who succumb to cancer per unit of population per year.

As the average life span of a population grows (because of advances against heart and respiratory disorders, infectious disease and so on), so does the cancer mortality rate. To calculate mortality trends over time, therefore, researchers adjust for the aging of the population.
With this adjustment—which, to be kept in mind, presents cancer medicine in a more favorable light — mortality rates have declined almost 30 percent since 1991.

This trend, according to cancer-industry boosters, shows that investments in research, tests and treatments have paid off. What boosters often fail to mention is that recent declines in cancer mortality follow at least 60 years of increases. The current age-adjusted mortality rate for all cancers in the U.S. is just under what it was in 1930!
Editor’s note: See the book "Dépistage du cancer du sein, la grande illusion" published by Thierry Souccar Editor[1] for a more detailed explanation of this mechanism concerning breast cancer.
In reality, the rise and fall of cancer deaths track the rise and fall of smoking, with a lag of a couple of decades. Smoking raises the risk of many cancers but especially of lung cancer, which is by far the biggest killer, accounting for more deaths than colon, breast and prostate cancer combined.
It was concluded that without reductions in smoking "there would have been virtually no reduction in overall cancer mortality in either men or women since the early 1990s.”

New treatments yield small benefits, big costs

Clinical cancer trials “have the highest failure rate compared with other therapeutic areas”.
Pharmaceutical companies keep bringing new drugs to market.
But one study [2] found that 72 new anticancer drugs approved by the FDA [3] between 2004 and 2014 prolonged survival for an average of only 2.1 months… A 2017 study concluded that “most cancer drug approvals have not been shown to, or do not, improve clinically relevant end points,” including survival and quality of life.
The authors worried that “the FDA may be approving many costly, toxic drugs that do not improve overall survival”.

Screening leads to overdiagnosis and overtreatment

The cancer industry, aided by celebrities who claim that tests saved their lives, has convinced the public that screening for cancer is beneficial. The earlier we can detect cancerous cells, the more likely it is that treatment will succeed, John Horgan explains here one of the most significant findings of the past decade which is overdiagnosis. Many people have cancerous or pre-cancerous cells that, if left untreated, would never have compromised their health. Autopsies studies shown [4] that many people who die of unrelated causes harbor cancerous tissue.

Tests cannot reliably distinguish between harmful and harmless cancers. As a result, widespread testing has led to widespread overdiagnosis, the flagging of non-harmful cancerous cells. Overdiagnosis leads in turn to unnecessary chemotherapy, radiation and surgery.

Gilbert Welch was one of the first who brought the overdiagnosis to the light and called it « unfortunate side effect of our irrational exuberance for early detection.”
Editors’s note : In France, Bernard Junod [5], an epidemiologist, teacher and researcher at the Ecole des Hautes Etudes de Santé Publique de Rennes, was, together with Dr Bernard Duperray, a whistleblower on over-diagnosis in France concerning breast cancer screening. Mammograms and prostate specific antigen (PSA) tests have led to particularly high rates of over-diagnosis and over-treatment of breast and prostate cancer.
Adding together the harmful and lethal effects of screening, any benefits of screening "are outweighed by the deadly damage due to over-diagnosis and false positives" according to breast cancer specialist Michael Baum [6], co-founder of the screening programme in the UK, who is currently calling for the discontinuation of these programmes, which he believes could shorten more lives than they prolong.

For one man whose life is prolonged, many others will experience false positive results with subsequent additional tests, eventual prostate biopsy, over-diagnosis and over-treatment, and treatment complications such as incontinence and erectile dysfunction.
The prostate specific antigen discoverer, pathologist Richard Ablin, called the PSA test a "profit-motivated public health disaster."

All-cause versus specific mortality and « torturing the data »

Studies of tests for a specific cancer generally look at mortality attributed to that cancer. Mammograms are thus deemed effective if women who get mammograms die less often from breast cancer than women who do not get mammograms. This method can overstate the benefits of tests, because it might omit deaths resulting, directly or indirectly, from the diagnosis. After all, surgery, chemotherapy and radiation can have devastating iatrogenic effects, including heart disease, opportunistic infections, other forms of cancer and suicide.

Rather, reference should be made to studies that measure "all-cause" mortality, as they account for the deleterious effects of treatment. A 2015 [7] meta-analysis by epidemiologist John Ioannidis (renowned for bringing the scientific replication crisis to light) and others found no reductions in all-cause mortality from tests for cancer of the breast, prostate, colon, lung, cervix, mouth or ovaries for asymptomatic patients.

In a recent editorial in the European Journal of Clinical Investigation, Ioannidis and four co-authors argue that cancer screening (especially mammograms and PSA tests) does more harm than good and should be abandoned. [8]

Survival rate

Often are pointed out improvements in survival rates, the length of time between diagnosis and death.
Survival rates for some cancers have indeed grown as a result of more widespread and higher-resolution testing, which detects cancer earlier.
But this doesn’t mean that people live longer as a result of early detection. They simply live longer with a diagnosis of cancer, with all its harmful emotional, economic and physiological consequences. (Explanation of survival rate here [9])
Using survival rates to promote tests is an example of what is have called “torturing the data» and for this article’s author, this a case of monstrous malpractice.

Corruption in the cancer industry

At USA, according to oncologist Vinay Prasad (@VPrasadMDMPH ; very active on twitter, Editor’s note) many cancer specialists accept payments from firms whose drugs they prescribe.
This practice "leads us to celebrate marginal drugs as if they were game-changers," Prasad argues. "It leads experts to ignore or downplay flaws and deficits in cancer clinical trials. ”
The desire of oncologists to produce monetizable findings might also compromise the quality of their research. A 2012 study of 53 “landmark” cancer studies found that only six could be reproduced.

Solution? Gentle cancer medecine?

The author pleads in favor of a medecine that adopt new therapies “when the benefit is clear and the evidence strong and unbiased.”
He pleads in favor of what some will call as conservative medicine that defines itself as a medicine that resists what is commonly and historically established, that knows how to say "stop" and arm itself with a lot of patience for those who want more medicine in a time where nobody is in favor of this attitude.
This meaning less testing, treatment, fear-mongering, military-style rhetoric and hype.
It would recognize the limits of medicine, and it would honor the Hippocratic oath: first, do no harm.
The patients must help these conservative physicians. We must recognize the limits of medicine and the healing capacities of our bodies, (dormant, non-evolving, spontaneously regressive cancers).
We must resist tests and treatments that have marginal benefits, at best.
We may never cure cancer, which stems from the collision of our complex biology with entropy, the tendency of all systems toward disorder.
But if we can curtail our fear and greed, our cancer care will surely improve.

According to Horgan, the fact to recognize the human body’s “inherent healing properties" and to acknowledge “how little effect the clinician has on outcomes” will make that physicians will thus protect themselves against their greatest foe—hubris, which is vanity.

References

[1] Extract from book of Bernard Duperray
Epidemiologists have the choice between two reference populations, the population of Europe or the world. The choice of the standard (“Europe” or “World”) induces wide variations in mortality.
“World” rates based on a younger population are generally lower than “Europe” rates reflecting an older population.
Depending on the standard chosen, the rate for the same population appears more or less high.

In France, the rates used most often by the InVs are the «Monde» rates (purple curve on the figure). The «Monde» standard tends to minimize the mortality rate for a country like France because it does not correspond to the structure of the French population. Moreover, according to Bernard Junod, age standardisation is subject to caution in describing a variation in mortality when the variations for the same age group are not uniform.
To assess the evolution of mortality in France in the fairest possible way, Bernard Junod chose to take as «standard» the age distribution of the population residing in France in 1992, that is to say in the middle of the period studied (1980 to 2005).
It thus obtained a standardized annual mortality rate by age in France per 100,000 women of 32.6 in 1980 and 32.9 in 2005, thus stable over this period.

In summary, here is what can be unquestionably retained from Figures 13 and 14:
• Between 1950 and today, the annual number of deaths and the crude rate of mortality from breast cancer have not decreased;
• Standardized rates “World” (purple curve fig 14) and “Europe” (blue curve fig 14) continuously increase in France until 1993 and then decrease while the crude rate stabilizes.

Let us now look again at figure 14. A surprising fact concerns us. The standardised “World” and “Europe” mortality rates of today, while falling, are still higher than those of the 1950s. Some would argue that comparing the current rates with those of 1950 is questionable because of the unreliability of the data at that time. It is possible, but then what about the fact that the standardized rates in 2006 were at the same level as those in 1970 according to the death registry which refers since 1968 (date of the creation of CépiDc, the Centre for Epidemiology on Medical Causes of Death)?

[2] https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/1891387
[3] https://www.fda.gov/
[4] https://cancer-rose.fr/2017/12/14/frequence-des-cancers-latents-de-decouverte-fortuite/
[5] https://formindep.fr/apparence-et-protestation/
[6] https://cancer-rose.fr/2019/08/08/synthese-detudes-un-exces-de-mortalite-imputable-aux-traitements-lemportant-sur-le-benefice-du-depistage/
[7] https://www.researchgate.net/publication/271022752_Does_screening_for_disease_save_lives_in_asymptomatic_adults_Systematic_review_of_meta-analyses_and_randomized_trials
[8] https://onlinelibrary.wiley.com/doi/full/10.1111/eci.13062
[9] https://cancer-rose.fr/2019/05/21/peurs-et-croyances-histoire-naturelle-de-la-maladie-survie/