What are the views?

"None of us is as smart as all of us " - Ken Blanchard

Below you can find the analyses of our structured stakeholder engagement interviews. The stakeholders are potential end-users and experts in the field of prostate cancer and diagnostics. The analyses show two different points of interest: the consumers are interested in getting an easily accessible test. The experts are more interested in a test incorporated in a more holistic implementation. The overall conclusion is that there is room for improvement in the testing for prostate cancer. The common aim is, therefore, an improvement of general health care and diagnostics.

We reached out to some experts who have been working in Prostate cancer for ages and asked them for their views, opinions and inputs in regard to prostate cancer in general as well as our project specifically. They were

Dr. Divya Ajay: MD and Assistant Professor of Urology at the University of Rochester, researching radical prostatectomy.
Niels Einer-Jensen: Chairman of the Medicinal Jury in PROPA (an NGO for patients of prostate cancer in Denmark).
Louise Helskov Jørgensen: Ph. D. and Lector in the Department of Clinical Biochemistry and Pharmacology at University of Southern Denmark.
Dr Søren Harnow Klausen: Professor of Philosophy at University of Southern Denmark, researching life quality among elderly people.
Signe Benzon Larsen: post-doc at the University of Copenhagen, researching prostate cancer survivors.

This is a summary of the views expressed;

What are your thoughts on (1) the individual/societal consequences of false positives and (2) the individual/societal consequences of false negatives?

With the article Reflective Equilibrium & Prostate Cancer, the issue of false positives and false negatives seems pretty well covered. The conversation leads to the explication of some of our presuppositions:

"At a societal level, false positives contribute to unwarranted procedures resulting in significant unnecessary costs for government-funded and private insurance-funded healthcare systems, which in turn contribute to tax and insurance premium increases. False negatives may contribute to delays in treatment, which can result in possibly more advanced disease and consequently more complications from treatment and worse outcomes." (Dr Divya Ajay, University of Rochester)

Divya mentions the economical aspects of false positives. PROSTATUS can hopefully lower these unwarranted procedures, making health care more efficient and cheap, so that there is more time for everyone and treatment is affordable. Oddly enough, the same goes for false negatives: the more complications, the longer treatment etc., the more costly and time-consuming the treatment becomes. Though this is purely an “economic” argument, it is important to weigh it in, especially in times like these where the coronavirus illustrates how health care systems struggle to manage large-scale diseases.

On a personal level, the psychological impact and the need for treatment seem to be in conflict. It seems difficult to solve the problem. However, the lowering of the amounts of false positives and false negatives seems overall to be sought after: "A screening test based on a urine or blood sample must be able to separate the two groups without a grey zone of false-positive or false-negative results. However, a group will benefit from being found, they may undergo curative treatment or undergo treatment, which will prolong their survival with years. PSA testing creates a huge grey zone, a new test must eliminate/decrease the problem." (Niels-Ejner Jørgensen, Chairman of the Medicinal Jury in PROPA).

All and all, it seems like there really is a need for our test! At least in terms of getting a more precise, accurate and nuanced test result. But, if we think critically about the outcome, the test might be “too” good: the problem of over-diagnosis, which is partially a political and personal problem, emerges.

What are your thoughts on (1) more people getting diagnosed with - and hereby treated for Prostate Cancer and (2) systematized screening of prostate cancer and the results of such screening?

Let’s imagine that our test is the best test for prostate cancer (not that difficult, we’d say) with 100% accuracy and that it was implemented as a screening device in the healthcare industry. Suppose that every man above 50 years is to urinate in a cup every 5 years to test for prostate cancer. Imagine that every man gets diagnosed with prostate cancer by the age of 75 years. Is this a good or a bad thing? The interesting thing to note is that this problem arises even though the test would have no problems. The question is then more about what we are supposed to use a test for, not how it is. So how do we solve the problem of “the perfect test”? We differentiate between malignant and non-malignant cancer!

"Identification of many men that need clinical workup may prolong time to diagnosis and treatment, which could be harmful to men with aggressive prostate cancer. Furthermore, we need to be careful when we introduce a screening program because it is very difficult to withdraw. I think that a good screening program should be stratified based on the man’s individual risk profile (intensive screening among men with high risk and less, maybe even no, screening for men with low risk)". (Signe Benzon Larsen, post. Doc., University of Copenhagen)

The absence of a distinction between malignant and non-malignant cancer is the primary problem. This is a problem that our test might be able to solve! Besides, Signe mentions an interesting idea in regards to differentiating and prioritizing patients. Since the risk of prostate cancer is significantly higher in families with family-history, it would make sense to have a trial-project with screening for people who are genetically predisposed.

In regards to health politics – which of course is very different from country to country – it is important, like Signe mentions, to be careful of implementing screening procedures, especially when considering the problems of false positives/negatives. The implementation of a screening procedure, knowing that it would result in a lot of true positives (diagnoses), would practically make half of the male population sick at some point in their lives. This is neither of interest for the public, for the individuals or for the health care systems. Indeed, on a populational scale, ignorance seems to be bliss

"I am especially worried about the biopsies (infections, adherence, even death) in a group of men, which could live 10-20 years without serious problems." (Niels Einer-Jensen).

We know that older men are more at risk of developing prostate cancer 1) Do you think that the age and likelihood of not dying of the disease influences the procedure for, and data about, prostate cancer in general? 2) Do you think taboo hinders the diagnosis and treatment procedure? 3) What are your thoughts on testing people for disposition to develop prostate cancer, specifically in regards to false positives/negatives and over-diagnosis?

The concern for the older men, who are the far biggest majority diagnosed with prostate cancer, is first and foremost a concern raised from an epidemiological factor. This factor should play a role in every aspect of our project: from raising awareness, considering ethics, modelling enzymes, even down to the instructions that would come with the test.

It is also a consideration that possibly influences the data about prostate cancer. The statistics might very well be influenced by the pragmatic approach of not testing, for example, terminal men in palliative care, in order to not induce unnecessary concerns. However, this argument is highly speculative and ex hypothesi unsolvable.

However, one can consider the consequences of the CRAT-system, that is, testing for the disposition to develop prostate cancer. The tone in this particular subject is highly critical: "AS with all genetic disposition testing, this needs to be carefully considered since there can be many unwanted side-effects to an outcome. Especially if one turns out to be disposed to incurable diseases or as in this case, cancer that many may get but without ever knowing it. In my opinion, it is generally not a good idea." (Louise H. Jørgensen)

"Overdiagnosis and overtreatment are absolutely concerning in younger men since they are more likely to be affiliated to the work marked and be sexually active. This must be considered before implementing a systematic screening program." (Signe Benzon) and "no single test has become a routine part of my practice because I find that all this extra data just confuses patients and sometimes overwhelms them. Also going through insurance companies for preauthorization and payment is very cumbersome" (Divya Ajay)

Could our test motivate more men to go to the doctor?
Benzon thinks that “...if they must still consult a doctor, I do not think that it makes a difference whether it is a blood or a urine sample”. Jørgensen is not sure, but raises an important question: “do we need more men to go to the doctor with this?”, and Ajay “questions the utility of this”.

One thing to take from this is that we probably should have been clearer in our formulation of the question. But still, when considering the thought experiment of “the perfect test”, it raises the question of whether asymptomatic men actually need a diagnosis. Maybe the laissez-faire approach is not that bad after all. But it is, we believe, all things considered, preferable to make a non-invasive test.

Is the “private model” (see Proposed Implementation) even a realistic option?
Benzon believes the main responsibility of conducting the test, handling the diagnosis and informing of where the patient goes from there, lies with the health care system. This is surely a clear argument against the private model.

Jørgensen states that “the information that comes with the test, if it is to be taken at home, must be elaborate and cover all possible aspects also if a result is in a grey-zone. This is particularly important”. This we considered, with the hardware team, when we made the design for the manual. See Proposed Implementation (for the manual) and Reflective Equilibrium & Prostate Cancer (for ethical considerations on the formulation of test results). But Ajay points out the most important point: even though the PSA-test is highly inaccurate, it is “highly accessible”! This is surely a bigger problem for the PSA-test than for our project, simply (we believe) because our test is better. Therefore, if one believes that our test should not be accessible, then surely one must also believe that the PSA-test should not be accessible. In short: improvement of status quo is surely better than no improvement at all.

Is there a need for PROSTATUS?
YES! Benzon: “what we need regarding diagnosis is a clear indication of the aggressiveness of the disease at the time of diagnosis”, Jørgensen (in regards to the PSA-test, red.): “if a given patient is tested twice they may have cancer one day and not the other...the problem is also the side-effects, thus a less invasive, more precise test would be of benefit”, and Ajay thinks of the established test as simply “frustrating”. Again, our test would be a huge improvement!

What ethical problems would PROSTATUS have?
Here, the main concerns that are brought up in the conversation are brought up in Ethics as well. It shows that most of our presumptions, for example, that setting, results etc. would be crucial, were not that far off.

Is our product suitable for the market?
Here, we can see that the experts simply didn’t have enough information to consider our test. This showed that we needed to discuss this with the hardware group, which we did. See Proposed Implementation.

These considerations are crucial in the implementation of our project, especially if it is to be considered a “package” solution. The considerations can be accommodated, like Signe Benzon suggests, by “…men with a strong familial disposition, where early testing could be recommended”. By gathering the family history of prostate cancer, one can at least make a screening programme where (1) the male members of the families with a known disposition to develop malignant prostate cancer take the CRAT-system at, say, 25 years of age in order to check for disposition to develop malignant prostate cancer, and (2) men whose test results showed high disposition were to be systematically screened for malignant cancer with the PMT-system every, say, 3rd year or so. Hereby we have both a legitimate reason to check genetical disposition, and on this ground legitimate reason to check for prostate cancer. This model seems the “slimmest” implementation of our product, but at least it is, practically, ethically undisputable!
For more elaboration on what the criteria for implementation are, how they should be met etc., see Proposed Implementation

Early in the project development we established a clear vision that involving end-users throughout the project was crucial for a successful end-product. We stepped into the background and let voices of the end-users be at the forefront on topics such as prostate health, help-seeking behaviour and diagnosis procedures. With having a citizen science mentality [Science Communication] in mind our approach to the interviews was as a conversation-like setting.
We did our qualitative research by conducting 10 semi-structured interviews which were followed by transcriptions of the audio recordings and hermeneutic analysis. After each of us had analyzed the interviews, we compared the interviews with hermeneutic interpretation and thus investigated which topics and categories emerged frequently across interviews.
This we aimed to do with an explorative and inductive approach. The end-product of this is a summary, from which we have integrated the most important aspects of our product development.

The informed consent and Interview questions we used are as follows;

Our target group consisted of males of all ages and different ethnicities, as we prioritized diversity in age, ethnicity and socioeconomic status. To create the ground for comparison of the gathered materials, we defined four pillars which we should cover throughout the dialogues:

Associations and emotions towards prostate cancer.
Factors of testing, incl. privacy, test location, test design, validity, credibility, communication and ethics.
A speculative approach on making the informant elaborate on the “perfect doctors' consultation” as a progressive finish.
Creation of ground for further conversation on whether the dialogue sparked any new thoughts on the interviewee’s behalf.

These pillars provided us with new insights on citizen’s perspectives on prostate cancer and testing methods as well as uncovering blind angles from us being young students.
We chose to maximize the opportunities from our team having a variated background both in regards to nationality and academia. Thus, team members from Public Health, Philosophy, Design, Medicine, Engineering and Cultural Studies/Social Science conducted interviews in each of our other tongues being Nepalese, German, Danish and Arabic/Danish. To achieve a comprehensive analysis, team members of each discipline analysed the topics to their expertise which the summary sections reflect below.

Prostate Cancer association

Cancer is one word – but a powerful one. The results of the interviews show, with no doubt, that it is not only the disease that the interviewees are afraid of but the changes that come after a positive diagnosis as well. It is not only one person who is affected, but families and friends as well. Our research shows that men have a hesitant attitude when it comes to going to the doctor in time, and we find the same pattern when the participants in the interviews are asked to answer the same question, where one man clearly states that he does not like going to the doctor: “I think that the fear of mortality and “bad news” are the main restraining factors here, especially primarily with men.”

Knowledge

There is a general tendency of lacking knowledge when it comes to prostate cancer and the following examinations, even though it is the most frequent type of cancer amongst men. If our interviews were representable of the risk group in general, the types of men can be divided into 3 subgroups:

The ones who do not know about the disease because they do not have any symptoms,
The ones who were forced to learn about it,
And the youngest ones who do not see the point in getting tested for something that is not relevant for them.

However, they all have in common that they want to learn more about it. As quoted, a man proposes a solution to get more men to the doctor, which is an annual health check: it “forces” men to, with time, become more accustomed to going to the doctor. It will cost some money now, but in the long run, it may save money if the men get healed before they get too sick.

Invisible cancer and enlightenment

As one of the participants points out, prostate cancer is a relatively “good” cancer if diagnosed early. Though, he also considered prostate cancer dangerous as it is detected/diagnosed in later life and remains invisible until it progresses to its final states. The advantage of screening in the early stage is crucial, but it seems that this information is not widespread. For one of the participants, the feeling of visiting the doctor would itself make him sick, and this feeling changed after he became a nurse.

Family, vulnerability, information sharing and taboo

Taboo was a factor that the interviewees reflected upon across three different national backgrounds and age. One man stands out, as he doesn’t think that taboo exists in regards to prostate cancer. But when relating it to himself, it becomes a personal topic, and he will only feel comfortable talking about prostate cancer within the family. He suggests that awareness campaigns could dismantle the taboos that might exist with prostate cancer. Another man also addresses educational programs as a tool to tackle symptoms being subjects of taboo. This is with the aim to detect severe health conditions earlier among men, and to arm men with a more profound knowledge of their own bodies. One man relates to himself as only after becoming a nurse his perception of his own health has changed. Now he won’t repress symptoms anymore, regardless of the nature of the symptoms.

There are varying needs and behaviours towards sharing information within or outside the family, as well as where the interviewees are seeking emotional support. It is commonly expressed that the procedure of testing for prostate cancer is not something they want to share feelings about. This goes for the disease itself as well. Confidentiality is more than once noted as an important factor, if sharing symptoms which are subjects to taboo is to be done.

Overall, it is expressed that more sharing of experiences will increase health awareness. This can lead to detecting malignant diseases early as well as breaking taboos. Few of the men expressed that they consciously create spaces for vulnerability between them and their male relatives.

Consultation culture, motive and fear

One man makes a very direct association between men not going to the doctor early enough and prostate cancer. This man also addresses the current procedure of diagnosing prostate cancer as actually being something that keeps men away from consultations regarding prostate health. A younger man specifies a wish for a test that can show the risk of getting prostate cancer. By that, he can avoid the rectal examination as far as possible. At the same time, such a test can increase behaviour where cancer can be detected earlier. Above all, he wishes to avoid the rectal examination. These objectives are shared by yet another man who also refers to the current diagnosis procedure as offensive and invasive.

An older man draws on himself expressing that even general procedures at a doctor clinic can withhold him from going to the doctor since he is afraid of what answers and revelations might show. Clear and visible symptoms make him go to the doctor earlier, and if the symptoms are located around the genitals he is embarrassed to be examined. He addresses his help-seeking behaviour as him “being a chicken”. Another man with a different nationality said that his general feelings when hearing the words "prostate cancer" was characterised by fear as it can change a life forever. Similar perceptions are addressed by a 56-year-old man, who points out that shyness and embarrassment in men should be treated as being OK but needs better management to not overlook severe diseases. This man also mentions that men must learn that a doctor’s clinic is not de-grading for them as men. It should be taught that it is OK for a man to expose oneself e.g. if getting a rectal examination.

Gender, masculinity, generation/tradition,age-related disease

Most of the interviewees point out that gender is a major factor in the before-mentioned issues. One suggests that annual health checks should be required for men like it is the practice with screening for some diseases for women. Another man shares this vision and defines the age 35 as the starting point. The before-mentioned nurse explained from his experience that men often wait for too long to go to the doctor, and it is often only when the pain becomes too severe that men book doctor consultations. This is an opinion shared across interviewees, as also described above. A 62-year old man perceives prostate cancer as something only older men get and that it is a disease “you die with and not of”. Drawing on the nurse’s experience, he also reflects on embarrassment playing an important role which he himself is influenced by. He draws parallels to the cultural upbringing of him as a boy and how it affects the perception of his health today. This he compares to women who, studies show, monetize their health issues more comprehensively than men do.

A 60-year-old man describes that the ability to fix oneself is a value rewarded to men. More frequent conversations among men could be a counterweight to this. Here, a same-aged interviewee tells that woman in e.g. a workplace could help men to better articulate their health conditions. It’s about establishing a language for vulnerable topics that are needed for men. This is also where one man draws a parallel to more structural challenges, such as the fact that men often work more hours than women. Therefore, going to the doctor is often downgraded on a busy day. This idealization of manliness is also addressed by another 56-year-old Danish man. He draws a parallel to the cultural notions of masculinity and how it is misperceived by society if men react to mild health symptoms.

Doctor and Patient relationship

For nearly all participants the credibility of the test seemed paramount. This meaning that the test being certified by an authoritative institution, like for example the country's health department, would be enough for some participants, whereas others would have more confidence if the test is administered by their doctors. A small discrepancy between when and if to see a doctor was shown, as some of those feeling no need to first see a doctor felt that they would rather get the results at a doctor’s consultation.

The biggest reason for not seeing a doctor was an embarrassment and uncertainty regarding the procedures the doctor would do to the patient. The uncertainty and lack of knowledge are scary for many men. Besides, it’s a lot about whether there is room to be vulnerable without being afraid of being judged or exposed. For nearly every participant it’s an awkward topic and a private matter, whereas there could be personal safety in having an at-home test. The individual relationship with one’s doctor also seems to make a difference. If you as a patient don't feel close to your doctor and aren’t familiar with the doctor and what to say, it can become even more awkward and feel more uncomfortable. Perhaps there needs to be some more positive feedback from the doctors regarding elderly men making doctors-appointments in general.

Many people are intimidated by not really knowing what to say, and therefore choose to skip the doctor visit, which could be an effect of socio-economic inequality, or at the very least a difference in educational levels. It also depends on how the doctor and the patient approach each other and how awkward topics are managed.

Ethics

When do personal interests meet common interests?
In one of the interviews, the subject mentions that it is, in almost a duty-like sense, the patient’s responsibility to get tested. Both for the patient’s surrounding and his own sake. Some political aspects are mentioned as well, for instance, that the health care system should make it as easy as possible to “do the right thing”. This phrase is repeated multiple times by the subject. We assume that it is meant to be understood as a way of saying that getting tested is the “right” course of action and that it is the maximization of utility for one’s own life – as well as other relations – that the subject has in mind when using this phrase. It demonstrates a nuanced and reflected way to think of the testing facilities – the covid-19 test strategy, with drive-in tests, is mentioned for comparison, although the similarities remain somewhat unclear. The notion of social responsibility could, however, in some aspects be problematic. The responsibility is put on the society, instead of the individual being the main driver for the actions. This is a difficult debate, and the subject's personal opinion seems to be somewhere in the middle of the "society vs. individual"-debate regarding getting tested.

However, the “reduction of inconvenience” can hardly be a point of disagreement, and it is a recurring theme in the interviews. Although this is common, there are some mixed opinions on how the results from a prostate cancer test is supposed to be shown. Some trust that an alternative test, if approved, can be taken at home. Others tend to be more towards letting the doctor conduct the testing. Others, again, express doubts on how they would like to get the results. Some prefer a comfortable home-setting, others a professionalized patient-MD-relation.

This is probably because of the obvious seriousness of testing positive for cancer. Although benign prostate cancer is relatively harmless, people may not be aware of this and simply associate it with a death sentence. The problem could be solved by the presence of a doctor. One of the subjects expresses that the test subject should definitely not be alone if a test answer is positive. This is a core issue of a test: you simply don’t know before you know the test result! The opinions on whether home-testing should be an option are relatively mixed.

Validation and credibility in an alternative test

Questions of validation and credibility have been a wide spoken subject in our interviews. It is essential and crucial that the users, the public and the healthcare industry trust an alternative test. A few keywords in this category are as follows:
validation – certification – credibility – governmental – scientifically approved – clinically-tested – recommendations by doctor and health care sector
If one or more of the above keywords would be implemented in an alternative test concept, then the interviewees have stated the following:
“I will get tested more frequently” - “I will trust the test” - “I will get myself tested for early-stage cancer”- “I will possibly begin conducting routine check-ups"
Most of the interviewees state that if self-test results are negative and the above requirements are met, then they will trust a self-test as an alternative to the established PSA-test. However, if the test results come back positive, they will be a bit sceptical and go to the doctor for an ordinary diagnostic procedure.

Disclosure of result in an alternative test

The disclosure of the results of the test has been a wide spoken topic in all interviews. There is a sudden ethical and psychological complexity attached to this topic. How should the users be given the result “negative/positive”? Since there is a possibility that the potential end-user might be alone and worried when taking the test, one suggestion is that the test must not reveal the results directly to the users. Maybe the user should not be alone when receiving the message “you got cancer!”.

Therefore, a variety of alternative scenarios have been discussed across the interviews.

The user takes the test and ships it back to the lab, a healthcare professional calls the user with the results.
The user takes the test and brings it with him to a doctor consultation where the results are revealed.
The test displays a cryptic answer (code) which can only be interpreted by a doctor. Hereby the user would need to call a doctor for the results.

Testing location for an alternative test

After insights from experts, we in the iGEM-2020 team decided to let it remain open whether we develop an actual self-test or clinical test. After analysing data gathered from the interviews, it seems clear that there is some incentive for the "private model" (see Proposed Implementation).

The home-test setting is complex due to the result disclosure and operation of the test. These aspects are elaborated elsewhere in this section. To mention a few key factors that the interviewees mention regarding a home-test:

I will get tested more frequently as a preventive measure with a home-test.
I will need instructions/consultation for a home-test, otherwise, I will not trust myself to use the test properly.
I do not like going to the doctor, therefore I prefer taking the test at home.
I feel embarrassed about going to the doctor with an “intimate” problem, therefore I prefer taking the test at home.
I do not want to get the results directly from the test.

In addition, it must be mentioned that there is a lack of consensus regarding this solution. We had an interviewee that informed us that if he had symptoms for prostate cancer, then he would go to the doctor and then he would prefer having the test conducted at a doctor consultation. Furthermore, an interviewee argued for the setting to be at the citizens home, by referring to research claiming that approx. 1,3m. humans worldwide cannot excrete in public constellations. This also supports the claim of acknowledging these citizens by making it a home test.

Test design of an alternative test

There was a consensus amongst our interviewees regarding a crucial need for a user-friendly test. More specifically, the design of the test should almost be self-explanatory, so minimum instructions are needed to understand the usage. The interviewees stated that the aesthetics of the test was not an important factor. Yet, a “stamp of validation” visual on the test would increase the credibility.

Another aspect, worth mentioning, is the hygiene since the test will operate using urine from the user and possibly elders with possible reduced motoric functions, the liquid elements of the test must be strictly contained. An interviewee furthermore stated that if shipping was involved in the testing process, the test should be relatively small to reduce shipping costs.

A few key factors regarding the design is the following:

The design must be very simplistic and require minimum instructions.
It is vital for the usage of the test, that it is very user-friendly.
It must be relatively small in size due to potential shipping costs.
Due to potential mass-production, biodegradable and environmentally sustainable materials are preferred.

References

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