Revision as of 12:49, 29 October 2017

Human Practices - Silver

In earlier discussions with specialists, we gained first insights on how our project would influence the treatment of patients. But what do they themselves think of our idea? In order to investigate this, we proposed to invite several patients to discuss our project. However, talking to patients is not something you go over lightly.
After receiving approval from the ethics committee of the UZ Leuven, we planned the overall course of the interviews in detail. The proposed questions were then reviewed by professor Monbaliu, who has already helped us earlier in the project. By performing patient interviews, we have gained insights in the daily lives of patients and learned of their opinion about HEKcite and the device, which would enable them to check the level of immune suppressants continuously. This information helped us frame the impact of our project, allowed us to adapt the project to patients’ needs and may be interesting for stakeholders in the future. In earlier discussions with specialists, we gained first insights on how our project would influence the treatment of patients. But what do they themselves think of our idea? In order to investigate this, we proposed to invite several patients to discuss our project. However, talking to patients is not something you go over lightly. After receiving approval from the ethics committee of the UZ Leuven, we planned the overall course of the interviews in detail. The proposed questions were then reviewed by professor Monbaliu, who has already helped us earlier in the project. By performing patient interviews, we have gained insights in the daily lives of patients and learned of their opinion about HEKcite and the device, which would enable them to check the level of immune suppressants continuously. This information helped us frame the impact of our project, allowed us to adapt the project to patients’ needs and may be interesting for stakeholders in the future.

Patient interviews

Introduction about our team and an explanation about the iGEM competition.

Question 1: What is your experience using immune suppressants?

All participants have the same answer: There is more to organ transplantation than meets the eye. After the surgery, not all problems are solved as you would expect, but new ones arise. Some of these issues are side effects, caused by immune suppressants. Among the most frequent side effects are insomnia, easy bruising and bleeding, a tingling sensation on the skin, infection of the joints, et cetera…

Question 2: Would you like to see a decrease of the amount of blood samples that needs to be drawn?

Most participants answered that they experience only mild discomfort from drawing blood. This is explained by the fact that blood drawings serve many purposes: When the participants go to medical consultations for blood drawings, the concentration of immune suppressants is just one of many variables analysed. This means that our device would most likely not reduce the total number of hospital sessions and the discomfort of blood drawing. This raises the question whether the device would be helpful for transplant patients. Luckily, this question was answered in the continuation of the interview.

After this question, we explained that it is important that blood levels of immune suppressants remain constant. Currently, blood samples are taken every week or in intervals of up to three months, dependent on the amount of time that has passed since the transplantation. Our goal is to develop an easy method that enables patients to test their immune suppressants at home, at any given time. This would lead to a better follow-up, and would allow the doctors to react to unexpected changes in concentration that would otherwise remain undetected. This way, the risk of organ rejection will be reduced.

Question 3: In which way do you think this device could influence your quality of life?

Despite the fact that all patients agreed that our project could increase their quality of life, the opinions on how it would affect their lives differed among the patients. Some of them think it would influence their life in a positive way as it could offer them piece of mind. Risk of rejection by the body increases as more time passes, and by then, most patients only visit the doctor once every three months. Therefore, they think the possibility of checking the level of immune suppression on a daily basis would give them comfort and reduce their stress levels, and it would also enable the doctors to react quickly to changes that would otherwise remain undetected for three months. Others shared the opinion that, while our project would not influence their lives directly, they think that our device could be a general advance in the organ transplantation field. When the risk of rejection of an organ could be lowered, this would ease their mind indirectly. Hearing from patients that this device could have an impact on their lives motivated us even further to complete our project successfully.

In order to do these daily measurements, a small device would be placed under the skin, containing living, genetically modified cells that respond to the concentration in the blood.

Question 4: Would you be willing to undergo this procedure if this could lower your risk of rejection? What is your opinion about the device containing genetically modified cells?

All responses of the patients were positive. They were indeed willing to undergo the procedure if this could lower the risk of rejection of the transplanted organ. A crucial consideration is that the device would be placed during the transplantation process. Most patients were tired of the various medical interventions, and would like to avoid undergoing surgeries that were not strictly necessary, as they inflict a lot of pain and are a cause of frustrations.

When asked about the genetically manipulated cells in the device, all patients reacted positively. As long as they are given sufficient information and are made aware of all the consequences and risks that result from the genetic manipulation, they would be willing to use the device.

Question 5: Would you be willing to participate in a clinical study to assess this device during a case in which you do not know if this could lower the risk of rejection?

The interviewed patients told us they would like to help scientific advances to improve the lives of future transplantation patients. Some of them mention that they have already participated in clinical studies in the past, and indicate that they are open to new developments. Therefore, two of the four patients would be willing to participate if a trusted transplantation doctor, such as professor Monbaliu, supported the study. The other two patients were more hesitant and they would only consider participating in case the risks were minimal and well known.

Question 6: According to professor Monbaliu, patient compliance is a problem in the organ transplantation field, especially some years after the surgery. The device could alert you when you have not taken your drugs yet by sending out notifications. Do you think this could be a helpful reminder for you when you forget to take your medicine or be helpful for taking your medicine at the same time on a daily basis?

The patients we talked to have received their transplants 2 to 7 years ago. However, they all told us that they have never forgotten to take their drugs, and this is no issue for them. However, the immune suppressants have to be taken at specific time points. The patients admitted that, as more time passed after the organ transplantation, they tended to take their drugs at less specific time points. These inaccuracies occur especially on holidays or special occasions, as it is difficult to take a medicine at the exact same time every day. Therefore, the patients see our device as a useful system, as it could give out a notification on their computer or smartphone.

Ethics

When our team was assembled and we started brainstorming about our project, we already appointed several persons as our ethics team. They had to try and keep an eye on the different topics we were focusing on and steer us in the more ethical direction. After our definitive project was chosen, the ethical work was far from done. What we, as a team, thought to be ethical might not be received as ethical by other experts or the general public. That is why we decided to go one step further and we addressed different ethical specialists. However, we wanted to incorporate different perspectives and not only the view of biotechnological companies. This is how, we started our search for spokesmen who could give us more insight in the ethics of our project but also in the more general ethical view on genetically modified organisms.

Our first meeting was with René Custers who is a regulatory and responsible research manager at VIB. VIB stands for Vlaams Instituut voor Biotechnologie, it is an important Flemish institution that conducts research in biotechnology and is an important partner of different companies and Flemish universities. René Custers helped us by giving us several important questions we should consider before proceeding with our project.

- HEK cells originated from an aborted human embryo, is this ethically correct?
- HEK cells were immortalized with different adenovirus genes, what would be the effect if these cells were introduced into the body?
- Is it ethical correct to gain money from widely used cells in research such as HEK cells?
- Would we need to test our device in animals before starting clinical studies?
- How invasive is our device? Resembles it the implantation of a pacemaker or does it come close to cell therapy?

All these questions seemed very relevant to us which is why we decided to do a small ethical debate within the team. This debate made us more aware of the different difficulties that go together with research in general but also specifically the ones regarding HEKcite. We based the debate on the different questions we received from René Custers, every question was asked one by one and every team member was allowed to give his/her viewpoint about the topic.

HEK cells originated from an aborted human embryo, is this ethically correct?

The whole team was quite level-headed regarding this question, we all agreed that using these cells should be allowed. For instance, HEK cells helped in answering many scientific questions that could might have remained unanswered if these cells were never used. However, there are strict regulations needed before using cells from human embryos is ethically correct. First of all, we all thought that consent from the mother was of utmost importance. Next to this, anonymity of the origin of the cells should be guarded at all times which protects the mother from possible discoveries in the embryo’s DNA and from possible societal reactions to her decision.

HEK cells were immortalized with different adenovirus genes, what would be the effect if these cells were introduced into the body?

This question was not answered by the team but by Bernard Schneider who gave us valuable information regarding the encapsulation device. He notified us that HEK cells are not allowed to be introduced into the human body for the main reason that they are immortalized with adenovirus genes. HEK cells in our capsule could become infected with adenovirus, if the adenovirus genes already present within the HEK cells come in contact with the infectious adenovirus, the possible consequences are not yet known. We as a team fully support that decision which is why we did more research about other cell types that can be used in the capsule. (link naar encapsulation text?)

Is it ethical correct to gain money from widely used cells in research such as HEK cells?

This question was answered by René Custers himself, he said that it has recently been approved to patent findings with HEK cells or other commonly used cells. The team supports this decision since we know that patents are crucial to stimulate innovation. Genetic modification and synthetic biology are the future which means that using certain cell types for genetic modification has to be allowed.

Would we need to test our device in animals before starting clinical studies?

Again, the whole team agreed, we would use biocompatible materials that are already extensively researched in clinical studies and animal testing. However, we think safety studies in animals are of great importance to verify the effect of the cells on the body if they could escape the confinements of the capsule.

How invasive is our device? Resembles it the implantation of a pacemaker or does it come close to cell therapy?

On this topic, the team did not quite agree, some members thought it resembled the implantation of a pacemaker while others thought it leaned more towards cell therapy. The biggest concern was: what if the capsule breaks and cells enter the body? Every team member agreed that first research had to be conducted to establish the possible consequences. However, some of them agreed that if this appeared to be safe, our capsule would more resemble a pacemaker. While other members were of the opinion that if indeed cells escaping was not dangerous, these were still genetically modified cells. In the end, we did not come to a consensus. Not reaching this consensus was not regarded as a negative point but as something we can still learn from. Using genetically modified cells in medicine is a difficult topic were ethics and science have to go hand in hand to determine the new way forward.

After this ethical debate, we were more determined to dig a little deeper into the world of ethics but also look at the different regulatory processes needed to start a clinical study. This is why we scheduled an appointment with the ethical committee of the university hospital of Leuven. The ethical committee gave us more information about the different juridical and regulatory procedures needed to start a clinical study, if you want to read more click here. On the other hand, they also gave us some more aspects we could think about. Such as the benefit-risk analysis, you should always keep in the back of your mind. It is important that patients always receive more benefit from the capsule than they are in risk of different complications. We did think about the complications such as the breaking of the capsule, infection or possible wrong read-outs. However, the ethical committee also pointed us in the direction of the psychological effect of our device. Some patients may find it beneficial to have more control regarding their illness but this may have the opposite effect on others. Patients could experience difficulties with having this much control or maybe would not like to know about their physical status every moment of every day. This made us think about the fact that with our device also an important psychological assessment should be made. The benefit should always exceed the risk and this is the psychical risk as well as the psychological risk.

After our meetings with the René Custers and the ethical committee, we assessed the information we already received and the different angels we received it from. René Custers gave us some more insight in the ethical view of a biotechnological company while the ethical committee gave us the viewpoint of a hospital. We felt that another important perspective was missing: the government. After sending various e-mails to a wide range of authorities, we were able to schedule a meeting with Johan Hanssens, the secretary-general of the department of economy, science and innovation in Flanders.

Johan Hanssens was able to give us more insight in the role of the government regarding genetically modified organisms. However, he told us that in Belgium the ethical decisions were mostly made by the different institutions and hospitals themselves. When it comes to regulatory decisions all of these are made by the European Union and are eventually implemented in the Belgian law. Momentarily Europe is very focused on responsible research and innovation, RRI. This new form of research implements the opinions of the different stakeholders such as doctors and patients in very early stages of research, to ensure that the conducted research has societal relevance. Johan Hanssens told us that Belgium as well as Flanders are searching for a way to have a more global body that could oversee the different ethical questions that are now overseen by the different hospitals and institutions themselves. Which means that the ethical debate could be done in a more structural and global way to ensure that Flanders and Belgium react in a unified way concerning difficult but also important topics regarding genetically modified organisms.

A biotechnology company, a hospital and the Flemish government, three different meetings and three different perspectives on genetically modified organisms. We, as the KU Leuven team, were very honoured to be able to hear these different perspectives and have the possibility to integrate these angles into our research: from different ethical questions, regulatory necessities from the ethical committee to RRI from the European Union. We discussed the different ethical questions given to us by René Custers in an ethical debate, we did research about the regulatory conditions to start clinical studies and by talking to doctors and patients we tried to do RRI as suggested by the European Union. All these aspects made not only our science more valuable but also taught the team that science is not something that stands alone but is also determined by the needs of society and that we have the honour to answer to those needs.

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              After this ethical debate, we were more determined to dig a little deeper into the world of ethics but also look at the different regulatory processes needed to start a clinical study. This is why we scheduled an appointment with the ethical committee of the university hospital of Leuven. The ethical committee gave us more information about the different juridical and regulatory procedures needed to start a clinical study, if you want to read more click here. On the other hand, they also gave us some more aspects we could think about. Such as the benefit-risk analysis, you should always keep in the back of your mind. It is important that patients always receive more benefit from the capsule than they are in risk of different complications. We did think about the complications such as the breaking of the capsule, infection or possible wrong read-outs. However, the ethical committee also pointed us in the direction of the psychological effect of our device. Some patients may find it beneficial to have more control regarding their illness but this may have the opposite effect on others. Patients could experience difficulties with having this much control or maybe would not like to know about their physical status every moment of every day. This made us think about the fact that with our device also an important psychological assessment should be made. The benefit should always exceed the risk and this is the psychical risk as well as the psychological risk.
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