This article proposes a synthesis of two points of view of Dutch academics written for a medical journal, then the translation of each piece is accessible by clicking on the authors' names.
A critical look at screening
Article by R. Giard
Article by Y. van der Graaf
A critical look at screening
Synthesis by C.Bour
In June, two Dutch academics each wrote a critical review of screening with the contemporary perspective of 2022, published by the medical journal Nederlands Tijdschrift voor Geneeskunde (NTvG).
NTvG is the leading medical journal in the Netherlands, published weekly, and one of the oldest journals in the world, based in Amsterdam. The journal aims to create a global medium for health professionals to exchange ideas, knowledge, and opinions and publish reviews and commentaries of research articles.
The editor-in-chief is Yolanda van der Graaf, author of one of the two perspectives. Yolanda van der Graaf is a professor emeritus at the University of Utrecht and a clinical epidemiologist. Her article describes the hidden risks of screening.
van der Graaf Y. De verhulde risico’s van screening [The hidden risks of screening]. Ned Tijdschr Geneeskd. 2022 Jun 13;166:D6760. Dutch. PMID: 35899724.
Raimond Giard is a professor emeritus, clinical pathologist, and clinical epidemiologist in Rotterdam and has written a critical view of screening under the title “A critical view on cancer screening: do we see the elephant in the room?"
Giard RWM. Kritische blik op kankerscreening [A critical view on cancer screening: do we see the elephant in the room?]. Ned Tijdschr Geneeskd. 2022 Jun 13;166:D6926. Dutch. PMID: 35899737.
Key points common to both authors
1° a new approach to screening is needed
For these two authors, there is a concrete system based on which it has been possible to decide that it is useful to introduce cancer screening: the Wilson and Jungner criteria published in 1968, which the WHO uses as a reference. But there is no system for deciding when it is preferable to stop screening or change the approach now that we are confronted with certain realities of screening and know its drawbacks.
For both authors, the criteria are a bit dated and should be reconsidered and re-evaluated.
For van de Graaf, there is even a serious lack of compliance with these criteria for some screenings, with some not complying with the conditions set out by Wilson and Jungner.
But what does the WHO use as criteria to determine the validity of a screening? The 10 criteria retained by the WHO are :
- The disease studied must be a significant public health problem
- The natural history of the disease must be known
- A diagnostic technique must be able to visualize the early stage of the disease
- The results of the treatment at an early stage of the disease must be superior to those obtained at an advanced stage
- Sensitivity and specificity of the screening test should be optimal
- The screening test must be acceptable to the population
- The methods for diagnosis and treatment of abnormalities found in screening must be acceptable
- The screening test should be repeatable at regular intervals if necessary
- The physical and psychological burden of screening should be less than the expected benefits
- The economic cost of a screening program should be outweighed by the expected benefits
For the Dutch authors, certain diseases are no longer a significant public health problem. Certain screening tests are no longer acceptable to the population, given their adverse effects. The physical and psychological harms are no longer lower than the expected benefits, which leads them to conclude that participants in screening programs should be given honest information, that if the benefits of screening are indeed overestimated and the harms underestimated, it is certainly time to reconsider cancer screening with an open and independent vision.
Several studies have argued that a universal population screening approach, particularly for breast cancer, is no longer tenable," says Giard. We need a new and independent evaluation of screening practices.
This analysis had already been expressed in a publication in CMAJ in 2018 that we had synthesized and commented on.
Wilson and Jungner's principles are getting dated, according to the authors of the CMAJ article. There is currently a need, they said, for a clear and consistent rationale to guide the use of various types of evidence toward a decision to screen. It is time to modernize these principles for explaining and discussing population-based screening. This modernization should contribute to informed decisions and better information about screening for the population in the future.
Our commentary echoed this, saying that the principle of informed choice, promotion of autonomy, and protection of the rights of participants in screening is simple and inexpensive to implement.
Pictograms with absolute numbers (using a consistent denominator, such as benefits and harms per 1,000 screened) and visuals using the same scale for information on gains and harms are evidence-based.
2° What would be the right questions to ask, according to Giard and van de Graaf?
According to R. Giard, good reasons to reconsider screening could include
- Has there been any change in the incidence of the disease?
- Has the treatment of the disease become more effective?
- Are there better diagnostic methods available today?
- Are there new, more reliable results from research on the effects of screening?
- Do we now know better and more accurately what the adverse effects are?
- Can we assess the disease risk more accurately and screen more specifically?
A significant question to ask is: is screening for a specific disease worthwhile? Y. van der Graaf uses the example of lung cancer screening, a program currently under evaluation."A long time ago," she writes, "we decided that we were willing to pay 20,000 euros for a year of life saved, but now the question is what else we could do with that money. Virtually all smoking cessation interventions are feasible for a threshold value well below €20,000 per life year saved. By far, the most health benefits can be achieved in the field of smoking cessation in the Netherlands. The health benefits of screening programs are minimal compared to these."
3°Overestimation of the risk and overestimation of the impact of screening
Y de Graaf explains: "Only 3% of women die of breast cancer. The risk of dying from colon cancer is "only" 2%."
(The risk of dying from cancer must therefore be put into perspective with other probabilities of death, such as cardiovascular disease, which is 6X more likely than dying from breast cancer for women, Editor's note)
Most breast cancers do not cause death in women, even without screening. What matters is the risk of dying prematurely from breast cancer and how that risk is reduced by participation in screening," she writes, "which means knowing the real impact of screening on mortality.
What is essential is to know how many people need to be screened to prevent 1 death from cancer in question. For example, for breast cancer: "For every breast cancer death you prevent through screening, 1000 women need to be screened regularly. By implementing a screening program, over 100 women are treated unnecessarily. So the odds of unnecessary treatment are tens of times higher than that of a woman obtaining benefits from screening. The main problem is that this number is not adequately communicated to potential participants to screening."
In her article, Ms van der Graaf explains in detail the distortion of the perception of the beneficial effect of screening in the population and among health professionals, the benefits and impacts being largely overestimated and the adverse effects ignored.
For both authors, the adverse effects of screening, i.e., false alarms, over-diagnosis, and over-treatment, are major issues. They are high and should no longer be ignored.
For R. Giard, "it is breast cancer screening, in particular, that does not seem to live up to its supposed promise. Even after many years of screening, the incidence of advanced breast cancer has not decreased."
In Switzerland, Hong Kong, and France (see our articles under "citizen consultation"), among others, critical reports have been published calling for the abandonment of breast cancer screening in its current form.
Several studies have argued that a universal population screening approach is no longer defensible, particularly for breast cancer."
Van der Graaf writes, "most importantly, potential participants must be informed of the potential harms and small health benefits."
4° The financial stakes and the need for independent evaluation
But people's fear of cancer brings in a lot of money and demands many systematic examinations such as whole-body scans, which Y. van der Graaf explains are useless.
The practice of systematic scans is an excellent revenue model because the provider only makes diagnoses, with an excessive amount of unexpected results that nobody knows what to do with, useless for the patient but leading to a succession of other examinations. This is called "irrelevant results" in her article, i.e., fortuitous discoveries of uninvestigated and useless anomalies, whose discovery rate is extremely high and which will cause cascades of other investigations or systematic patient monitoring.
For both authors, screening must be evaluated by independent scientists, not by people who have been doing screening for decades and who have conflicts of interest.
It is also necessary to combat the proliferation of screening programs for which there is no scientific evidence, and financial gain is the priority.
According to Giard, re-evaluations of screening would require appropriate research teams, "broad-based," not only consisting of physicians but also social scientists, ethicists, methodologists, and health economists, and excluding those with financial implications for screening.
Article by R. Giard
A critical eye on cancer screening- Do we see the elephant in the room?
Giard RWM. Kritische blik op kankerscreening [A critical view on cancer screening: do we see the elephant in the room?]. Ned Tijdschr Geneeskd. 2022 Jun 13;166:D6926. Dutch. PMID: 35899737.
'A great deal of intelligence can be invested in ignorance when the need for illusion is deep'
Saul Bellow, To Jerusalem and back
Cancer screening promises health benefits, but it also delivers harm and costs. A substantial problem is the overdiagnosis of tumors not needing treatment. There are well-established principles for starting cancer screening, but we also need periodic evaluations and stopping rules. For that, we must have the results of methodic empirical studies with proper estimates of benefits and harms. Proponents of screening emphasize its advantages but hold back on its drawbacks. Several studies have argued that a universal population screening approach is no longer tenable, especially for breast cancer. We need a fresh and independent assessment of screening practices.
Conflict of interest and financial support: none declared.
Shouldn't we be taking a fresh look at cancer screening? 1-3 There is a system based on which it can be decided that it is useful to introduce cancer screening - see the WHO criteria of Wilson and Jungner - but not to determine when it would be better to stop or to adopt a different approach. For that, one needs both the correct methodology and the right data. Such an evaluation, intended to separate illusions from reality, should be periodically repeated.4
Cancer screening, part of public health care, involves significant conflicts of interest and biases. Proponents and opponents of screening can find outcomes in the pervasive medical-scientific literature on the subject that fit well with their stance. Rethinking its usefulness and necessity, therefore, requires independent and methodical researchers.3,4
Good reasons to reconsider may include: did changes occur in disease incidence?
Has the treatment of the disease become more effective? Are there better diagnostic methods now? Are there new, more reliable results from research on the effects of screening? Do we now know better and more precisely what the harms are? Can we assess the risk of disease more accurately and, therefore, screen more accurately?
Over- and underdiagnosis
As discussed in the NTvG, cancer screening tests show deficiencies in over- and underdiagnosis.5-7 The frequency of overdiagnosis of breast cancer is variably reported between 0 and 50%. 8 And the same research figures can be interpreted differently depending on whether you are an advocate or critic of screening.9 But there is no doubt that significant overdiagnosis exists; it occurs in at least 20% of all mammary carcinomas detected during screening.1,5
Underdiagnosis is evidenced by the occurrence of interval cancers, a possible "failure" of the screening test. As a solution to this is the search for additional or improved technology. In breast cancer screening, more sensitive imaging techniques are being sought, such as digital mammographic tomosynthesis and MRI, and the application of artificial intelligence in assessing mammograms. The danger is that with more sensitive diagnostics, even more, and especially smaller, abnormalities will be detected, resulting in even more overdiagnosis.10
What do you need to make a good assessment?
To properly assess the effects of screening, you need sound empirical data and especially outcome measures that are valid, reproducible, and sufficiently specific.11 Disease detection is not the goal, but a means. The intention is to gain life years or increased chances of cure. Cancer-specific mortality drops undeniably due to screening, but the absolute mortality within screened populations appears to decrease little or not at all. And there is still the question of whether an alleged survival is really the result of screening.5
Careful consideration of beneficial and adverse effects is a task for both those conducting the population screening and those participating in it.3,4 National screening programmes have been designed to ensure that the benefits of screening are carefully considered.3,4 National guidelines for cancer screening should explicitly state the desired relevant outcome measures. Still, they should also address the essential tradeoffs between the benefits and harms of that particular population screening. A recent systematic review showed that only a minority of those guidelines explicitly address this issue.12
Potential participants should be able to make an informed decision about whether or not to participate in screening. But who provides balanced information about the benefits and harms and how to address these? Information about the consequences of overdiagnosis, particularly the need for further invasive tests and surgical intervention, has been shown to make women more reluctant to participate in breast cancer screening.13
Evaluation of population-based cancer screening
Cancer is a heterogeneous disease, and population screening is a complex procedure. Divergent variables determine its outcomes. That is why a comprehensive evaluation is so complicated: what are its aims, who will do it, what will they investigate, and how? This requires an appropriate, i.e., broadly based, research team, that includes social scientists, ethicists, methodologists, and health economists in addition to medical professionals. Persons with financial or institutional involvement in screening should be excluded from such a team. 4
Essential to such an evaluation is greater participation by the target screening group: after all, they are confronted with negative consequences. How do they weigh up all the pros and cons? A Norwegian study, for example, showed that in breast cancer screening, the consequences of overdiagnosis and overtreatment negatively affected the quality of life of the women, expressed in quality-adjusted life years (qaly's).
Over and again, the harms of screening are not adequately considered; I call this the elephant in the room.1-3
Breast cancer screening, in particular, does not seem to be delivering on its supposed promises. Even after many years of screening, contrary to expectations, it appeared that the frequency of advanced breast cancers did not decrease.5 In countries including Switzerland, Hong Kong, and France, critical reports appeared calling for breast cancer screening in its current form to be stopped.2,4
Twenty years ago, the NTvG already organized a conference with critical reflections on cancer screening.
The problems identified and the conclusions reached then are still relevant today.15 If the benefits of screening are indeed overestimated and the harms underestimated, it is time to reconsider cancer screening in our country with an open-minded and independent view.
Conflict of interest and financial support: none declared.
Online article and comment at ntvg.nl/D6926
Rotterdam: em.prof.dr. R.W.M. Giard, clinical pathologist (n.p.), clinical epidemiologist and lawyer.
Contact: R.W.M. Giard (firstname.lastname@example.org)
Conflict of interest and financial support: none reported.
Accepted on May 18, 2022
Cite as: Ned Tijdschr Geneeskd. 2022;166:D6926
1. Adami HO, Kalager M, Valdimarsdottir U, Bretthauer M, Ioannidis JPA. Time to abandon early detection cancer screening. Eur J ClinInvest. 2019;49:e13062. doi:10.1111/eci.13062. Medline
2. Hochman M, Cohen P. Cancer screening: no longer the default. J Gen Intern Med. 2021;36:525-6. doi:10.1007/s11606-020-05781-7. Medline
3. Van der Graaf Y. De verhulde risico’s van screening . Ned Tijdschr Geneeskd. 2022;166:D6760.
4. Ropers FG, Barratt A, Wilt TJ, et al. Health screening needs independent regular re-evaluation. BMJ. 2021;374:n2049.doi:10.1136/bmj.n2049. Medline
5. Autier P, Boniol M. Mammography screening: A major issue in medicine. Eur J Cancer. 2018;90:34-62.doi:10.1016/j.ejca.2017.11.002. Medline
6. Van der Graaf Y. De verhulde risico's van screening. Ned Tijdschr Geneeskd. 2022;166:D6760.
7. Krom A, Dekkers OM, Ploem MC. Verlies de nadelen van screening niet uit het oog: zorgen over wijziging Wet op hetbevolkingsonderzoek. Ned Tijdschr Geneeskd. 2022;166:D6701.
8. Chaltiel D, Hill C. Estimations of overdiagnosis in breast cancer screening vary between 0% and over 50%: why? BMJ Open.2021;11:e046353. doi:10.1136/bmjopen-2020-046353. Medline
9. Njor SH, Paci E, Rebolj M. As you like it: How the same data can support manifold views of overdiagnosis in breast cancer screening.Int J Cancer. 2018;143:1287-94. doi:10.1002/ijc.31420. Medline
10. Jatoi I, Pinsky PF. Breast cancer screening trials: endpoints and overdiagnosis. J Natl Cancer Inst. 2021;113:1131-5.doi:10.1093/jnci/djaa140. Medline
11. Porzsolt F, Matosevic R, Kaplan RM. Recommendations for cancer screening would be different if we measured endpoints that are valid, reliable, specific, and important to patients. Cancer Causes Control. 2020;31:705-11. doi:10.1007/s10552-020-01309-w. Medline
12. Zeng L, Helsingen LM, Kenji Nampo F, et al. How do cancer screening guidelines trade off benefits versus harms and burdens of screening? A systematic survey. BMJ Open. 2020;10:e038322. Medline
13. Stiggelbout A, Copp T, Jacklyn G, et al. Women’s acceptance of overdetection in breast cancer screening: can we assess harm-benefit tradeoffs? Med Decis Making. 2020;40:42-51. doi:10.1177/0272989X19886886. Medline
14. Zahl PH, Kalager M, Suhrke P, Nord E. Quality-of-life effects of screening mammography in Norway. Int J Cancer. 2020;146:2104-12.doi:10.1002/ijc.32539. Medline
15. Giard RWM, Hart W. De pretenties en prestaties van kankerscreening, in het bijzonder voor borstkanker . Ned Tijdschr Geneeskd. 2002;146:1045-9 Medline
Article by Y. van der Graaf
The hidden risks of screening
Yolanda van der Graaf
With screening, the natural course of the disease should be altered to reduce mortality from that disease. Screening offers minimal benefit but has many disadvantages, like false positives, overdiagnosis, and psychological distress. The advocates of screening overestimate the importance of the disease and the effects of screening but neglect the disadvantages. But also, potential participants and medical doctors overestimate the effects of screening. Although considered important, the still valuable criteria by Wilson and Jungner are neglected by researchers and committees that approve screening. Even when doctors disapprove of screening, healthy people are willing to undergo body scans, although nobody knows how to deal with the many abnormalities detected. Screening programmes should be evaluated against other interventions and not simply by making models with many unproven assumptions. And most of all, the potential participants must be informed about the possible disadvantages and the minor effects on health.
Detecting disease before it gives symptoms must be better, right? 'Prevention is better than cure.' That seems like such a simple premise that many people do not need any proof for it. But the reality is much more complex.
Why is screening so attractive to citizens, healthcare providers, industry, and government, and why are the disadvantages so hard to find? In this article, I describe the principles of screening, overestimation of the risk of disease by the society, and the unfamiliarity of doctors and participants with the real effects of screening on health.
I then quantify the risks of screening and discuss why screening nevertheless remains so popular.
The principles of screening
With a simple screening test, we try to classify people without symptoms into high-risk and low-risk groups. Almost always, a second test is needed - for example, a biopsy - to confirm the presence of disease. After confirmation, we start treating the disease. The goal of screening is to change the natural course of the disease favorably. But this assumes that we know what this natural course looks like and that there is a latent stage in which the disease can be detected and treated.
Sometimes we detect the disease earlier, but we are still too late, and the participant only lives longer with the awareness of the disease. And sometimes, we detect tumors that someone will never suffer from.
So in tumors detected by screening, we can find a more favorable prognosis than in tumors detected because they gave symptoms. On the one hand, this may be due to a biological difference between the tumors, known as length-time bias. On the other hand, some survival gain is artificial because we pick up tumors in screening earlier than if we wait until they give symptoms. This phenomenon is the "lead-time" bias. That length and lead-time bias evaluate screening complex, so only comparative studies, often with more than ten years of follow-up, provide a good picture of the advantages and disadvantages of screening.
Wilson and Jungner already thought more than 50 years ago that "earlier" can only be better if a number of conditions are met.1
Although these conditions are always mentioned in Health Council reports, you only have to compare the current cervical cancer screening with these criteria to see that there has been a serious lack of compliance (Table 1). Cervical cancer is not a major public health problem, and there is a considerable discrepancy between the number of premalignant abnormalities detected and the number of women with invasive cancer. And because knowledge about the course of premalignant abnormalities is insufficient, there is widespread overtreatment.
It seems that with the upcoming legislation - the Preventive Medical Examination Act - the disadvantages of screening have already been brushed entirely under the carpet.2,3
Overestimating the risk of disease
In general, the risk of disease is quite overestimated. The Dutch Brain Foundation is trying to make us believe that. Dutch people has a brain disease.4 That seems like a lot until you read that 1.9 million Dutch people have a personality disorder, anxiety, or panic disorder. Sleeping badly suddenly turns out to be a brain disease. Even for cancer, the actual risk is overestimated.
Rarely is told what the 'lifetime' risk is of dying from cancer. Only 3% of women die from breast cancer. The chance of dying from colon cancer is 'only' 2%.
On the RIVM website, I read that 1 in 7 women will get breast cancer at some point in their lives. 5 That is irrelevant because most breast cancers do not kill women. Not even without screening. What matters is the risk of dying prematurely from breast cancer and how that risk is reduced by participating in screening. Moreover, the age at which one dies is an important fact lost when presented with the usual absolute numbers of a cancer type.
Overestimation of the impact of screening
Potential participants greatly overestimate the benefits of population screening. An extensive interview study with more than 10,000 participants that asked how much disease-specific mortality reduction population screening for breast and prostate cancer found that more than 92% of women overestimated the effects of screening by a factor of 10.6
In the Netherlands, more than 50% of women think that because of the screening program, more than 50 out of 1,000 women will no longer die of breast cancer. And 20% do not know. The correct answer: per 1000 women screened, 1 woman will die less from breast cancer. That answer was given by 1% of respondents.
Doctors also overestimate the effects of screening. 7 More than 50% of U.S. physicians were found not to understand the principles of screening. They thought that the higher number of tumors in the screened group was proof that screening is effective.
Three-quarters had never heard of lead-time bias. In a September 25, 2018, press release, Erasmus MC claimed that screening for lung cancer prevents thousands of deaths.8 The sobering numbers accompanying this optimism appeared a year later.9 But even if no medical profession sees the value of a screening test and there is not a shred of scientific evidence, people allow themselves to be screened.10 A good example of this is the so-called body scans that the commercial company Prescan which more than 150,000 clients have used since 2003.
The risks of screening are high
The effects of screening for cervical, breast, and colon cancer have been extensively studied. We know approximately the number of people who need to be screened to prevent 1 death from cancer in question. The main problem is that this is not adequately communicated to the potential screening participants. A much bigger problem is that of screening initiatives whose effectiveness is not even known, not to mention that there is an awareness of overdiagnosis and overtreatment.
For every death from breast cancer that you prevent with screening, 1000 women need to be screened regularly. Through a screening program, more than 100 women are treated unnecessarily .11,12 The odds of unnecessary treatment are thus dozens of times higher than that of a woman benefiting from screening. Recently, the percentage of women between 50-74 diagnosed with breast cancer by screening but who will never develop breast cancer was estimated at 15.4%.13
Why is a total body scan not useful?
Scans (CT and MRI) reveal much more than we would like. In particular, they map out aging. The potential benefit of the total body scan lies in the early detection of malignant tumors, vascular abnormalities, and calcifications. A priori, don't expect a body scan to be useful. For that, the prevalence of malignant tumors is too low; treating asymptomatic vasoconstrictions(carotid, coronary vessels) causes harm, and calcium in the coronary vessels may predict risk but does not mean that interventions are useful.16 Calcifications are simply a sum of the classic risk factors and interactions between genes and the environment. The big problem with the total body scan is the excessive amount of findings that no one knows how to deal with. A review of 15,877 patients showed the percentage of extracardiac results to be 44% (95%-BI: 35-54).17
A similar systematic review that included a total of 12,922 patients found the prevalence of clinically relevant findings was 13% (95%-BI: 9-18).18 The studies used a pragmatic definition of 'clinically relevant: findings that a clinician should look for (e.g., pulmonary embolus, cysts, larger nodules, lymphoma, suspicion of malignancy).
Characteristics that you would expect to influence prevalence, such as age, percentage of smokers, or field of view ("field of view"), were not explanations for the differences in prevalence. Probably because the definition of 'clinically relevant abnormality' is inconsistent.
But people's fear of cancer also generates a lot of money. 20 For convenience, no research is done on effectiveness; instead, recruiting claims are used. Under the guise that you will gain insight into your health in one day, people are seduced. For € 1250, you get 5 MRI scans - of the skull and brain, cervical vessels, chest, upper and lower abdomen - and laboratory tests. It's a great revenue model because the provider only does diagnostics. No follow-up research and no treatment. Prescan, a company that offers total body scans, throws the consequences of abnormal findings over the fence. The curative sector should take care of that.
Is screening worth the money?
Finally, a few words about the evaluation of screening: this evaluation compares screening with a situation where there is no screening. Such a comparison often lacks important data and uses complex models that almost no one can understand.
A long time ago, we decided that we were willing to pay €20,000 for a year of life saved, but today the question is, what else could we do with that money? Virtually all smoking cessation interventions are feasible for a significantly lower threshold value than the €20,000 per life year gained. By far, the most health gains can be achieved in the Netherlands regarding smoking cessation. These dwarf the health benefits of screening programmes.
Although screening has been practiced for decades, the disadvantages of screening are not adequately addressed. The reality is that 'earlier' is not always better. Proponents of screening cannot refrain from exaggerating the risk of serious disease, overestimating the benefits of screening, and ignoring large numbers of false positives.
The screening evaluation is currently deficient because it does not weigh whether much more health benefits can be achieved with the same costs but different efforts. Screening should be evaluated by independent scientists and not by people who have often been involved in screening for decades. In addition, the proliferation of screening programs for which there is not a shred of scientific evidence and for which financial gain is paramount should be vigorously opposed. But above all, participants in a screening program must be fairly informed. This journal made some very good suggestions for this back in 2009.
Online artikel en reageren op ntvg.nl/D6760
UMC Utrecht, Julius Centrum, Utrecht: prof.dr. Y. van der Graaf, klinisch epidemioloog.
Contact: Y. van der Graaf (email@example.com)
Accepted on May 5 2022
Cited as: Ned Tijdschr Geneeskd. 2022;166:D6760
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tomography: looking beyond the heart. PLoS One. 2012;7:e32184. doi:10.1371/journal.pone.0032184. Medline
19. Johansson M, Borys F, Peterson H, Bilamour G, Bruschettini M, Jørgensen KJ. Addressing harms of screening - A review of outcomes in Cochrane reviews and suggestions for next steps. J Clin Epidemiol. 2021;129:68-73. doi:10.1016/j.jclinepi.2020.09.030. Medline
20. In één dag inzicht in je gezondheid! Prescan. www.prescan.nl/?gclid=Cj0KCQiA9OiPBhCOARIsAI0y71AT0HHRx4u4UkvG5luXgrTUZBmKGxdbdMTrZ8Q6maDE2NGV3PYvVIEaAqhYEALw_wcB, geraadpleegd op 1 juni 2022.