Team:SDU-Denmark/Implementation

Implementation

"Health benefits should be prioritized in such a way that it is given higher priority to benefit those who are most disadvantaged." - Lasse Nielson

We ended the essay on expert correspondence with a suggestion of an implementation that was “ethically indisputable”. It can be said that health benefits should be prioritized to the most disadvantaged groups, and in our case, a genetic disposition is the factor that would make a person most disadvantaged regarding the development of prostate cancer.

How we envisioned our test's future

Prostate cancer rarely affects men under the age of 50 but the risk increases with age. When a man is around the age of 75 or above, the likelihood of dying with it rather than of it has increased and we have to consider if our test should include these men. They have every right to get tested. But what is the purpose? We do not want our test to increase fear.
On average (in 2012-2016 in Denmark) there were 4,505 new cases per year. Among those, 87% were still alive five years after being diagnosed with prostate cancer. Annually, about 1,178 die of prostate cancer. Hopefully, our test can detect prostate cancer at an early stage, so that the number of men dying of prostate cancer will decrease. Furthermore, an early diagnosis can hopefully contribute to a higher percentage of those who live after five years. The only downfall, if our test is more accurate to detect prostate cancer than the PSA-test, is that we might contribute to overdiagnosis. One way to solve this problem might be with an “age limit” for the screening programme – say from 50 to 70 years – where men, who would have died of prostate cancer as a direct cause, could have been diagnosed and treated [4].
Although the claim of making a screening programme on grounds of a genetic factor is prevalent, it is still political. This cannot be avoided when talking about what our project is supposed to be used for. But here we can make a core distinction between two models:



Considering the target group of 1.4 million men in Denmark (see Enterprenership under Hardware) the private model has a considerable market.
We must keep in mind that the most important thing is the credibility and validity of our test. For our test to realistically be able to replace the current “gold-standard”, the PSA-test, it has to be more accurate. The PSA-test has proven ineffective in reducing the mortality in screenings. We hypothesize that our test would be similarly ineffective, especially without a certain amount of epidemiological legwork and evidence, to identify the population that would actually benefit from this. Although a screening programme would be problematic, doing it with the established PSA-test would be downright catastrophic, which these statistics show:


When considering the private model, false positives and false negatives are unavoidable for all tests. A false positive can contribute to unwarranted procedures resulting in unnecessary costs for the healthcare system. Our test should lower these unwarranted procedures and make the healthcare system more efficient and cheap for the consumer. If the amount of false positives is too high, it may have a negative effect on how the healthcare system manages a large-scale disease. False negatives can result in a delay in treatment, which may result in advanced disease progression. This can result in a worse outcome for the patient. In the end, both outcomes, false negatives, and false positives, also have an economic impact. Besides the economic aspects, there is also the psychological impact that our test might have related to false positives and false negatives. Our test must be able to separate the groups of the false positive and false negatives from true positives and true negatives respectively. The PSA-test creates a grey-zone due to its imprecision. Our test should decrease this issue and be more accurate than PSA-test. For further elaboration on this topic, see Reflective Equilibrium & Prostate Cancer.
Overdiagnosis may result in an overflow of men needing treatment. This can prolong the time to diagnose and treat men with aggressive prostate cancer. Besides, if we introduce a screening programme, we have to be sure that it is the best solution for everyone involved. A suggestion could be to only screen those at high risk. The screening programme would then be a way to prioritize patients and prevent overdiagnosis. This means that our test must be able to distinguish between malignant and non-malignant cancer.
Regarding health policies in Denmark, it is important to be careful of implementing screening procedures, especially when considering the problems of false positives/negatives mentioned above. The implementation of a screening procedure, knowing that it would result in a lot of true positives (diagnoses) would practically make half of the population sick. This is neither of interest for the public, for the healthcare systems, or for the patient. Besides, the number of biopsies being performed in men, which may cause infections and in the worst case even death due to sepsis, would for many men be pointless, because these men could live 10-20 years without serious symptoms and even “outlive” their prostate cancer. This concern for the older men is first and foremost a concern raised from an epidemiological factor. The concern could be met through risk-stratification. Risk stratification should play a role in every aspect of our project from raising awareness, considering ethics, modeling enzymes, even down to the instructions that would come with the test. Due to the risk of getting prostate cancer, it is also necessary to reflect on our CRAT-system which is testing for the predisposition to develop prostate cancer. By gathering the family history of prostate cancer, one can at least make a screening programme where:

In regards to the private model, our tests are classified as medical equipment due to their ability to hopefully diagnose men with prostate cancer and their predispositions. Because our tests are classified as such, they need to be CE-marked*. In short, our products have to:


  1. Fall within the definition of medical devices,
  2. Meet the essential requirements for safety and performance and the labeling and instructions for use should meet the national language requirements,
  3. Have the technical documentation, including risk analysis, clinical evaluation etc. prepared,,
  4. Obtain Certification sterile Class I equipment or Class I equipment with measuring function from an organ,
  5. Be put in a market monitoring system and serious incidents when using the product to the Danish Medicines Agency (Lægemiddelstyrelsen) have to be reported,
  6. Be drawn up in a Community declaration of conformity, and
  7. Be registered at the Danish Medicines Agency [3].

Even if our tests fulfill these requirements, it will take time and many years before our products will be approved for use. The PMT-system will most likely be used on the same scale as the PSA-test and it may not be able to replace the rectal examination or the biopsy. The PMT-system may not be able to stand alone to diagnose potential prostate cancer, since this would require a tissue sample. You need verification. Our test will be able to help select which men should seek medical attention urgently and who should not, thereby reducing the number of men who get unnecessary rectal examinations and biopsies. The best implementation for our test will be if our test can help to get men, especially men who are at risk, to go to the doctor. In the private model, the test would be bought by the users, where they can take the test at home in privacy. Therefore, the test’s response should be along the lines of “go to the doctor for a further examination soon” if positive, or “go to the doctor if you continue to experience symptoms” if negative, and we leave it up to the user to seek advice at the doctor if they have any concerns about taking the test or otherwise have any concerns regarding prostate cancer. Since our test will be competing with the PSA-test, our test must be more accurate. As mentioned previously, the target groups are 1.4 million for the PMT and 730.000 for the CRAT in the private model. The numbers for the public model are much more unclear since it’s dependent on political decisions. By combining our CRAT and PMT tests, and the presented screening models, it may be possible to supplement it with the diagnosis of prostate cancer so more ultrasound examinations, rectal examinations, and biopsies can be avoided which has a socio-economic benefit. That would have a positive effect on the health system and the patients.



*A CE-marking shows that a product complies with EU rules and it declares that the product complies with all the legal requirements for CE-marking. Furthermore, a CE-marking presupposes that the equipment has a high level of safety, is suitable for its purpose, and the advantages of using the equipment are not disproportionate to the disadvantages.

References

  1. Nielsen, Lasse. 2020, p. 125 ‘Retfærdig Fordeling’ in Personlig Medicin: Klausen, Søren Harnow; Christiansen, Karin. 1st ed. København: Munksgaard; 2020. Own translation.
  2. Green, Sara; Vogt, Henrik; Brodersen, John. P. 190 ‘De raske patienter I personlig medicin: sygdomsforebyggelse og overdiagnosticering. in Personlig Medicin: Klausen, Søren Harnow; Christiansen, Karin. 1st ed. København: Munksgaard; 2020. Own translation.
  3. https://laegemiddelstyrelsen.dk/da/udstyr/lovgivning-og-vejledning/sundhedsstyrelsens-vejledninger/vejledning-til-fabrikanter-af-medicinsk-udstyr-i-klasse-i/#
  4. cancer.dk