Essential Human Practices

In our project this year, we built our Human Practices upon three essential foundations that guided us along our journey.

To begin, we were keen on making an accurate identification of the issue that we are targeting this year. As we know it is very important to highlight the specific problem from day one, to direct all the team’s efforts and creativity towards finding innovative solutions for it. As mentioned in our Project description, we aimed this year at finding a complete cure for Rheumatoid arthritis. All the aspects of this disease are explained and supported by a patient journey.
Next, we wanted to identify all the stakeholders relevant to our project. After various brainstorming sessions, our HP team came out with a list of all the potential stakeholders. Hence, we tried to reach out to them to understand their values and needs. We were also keen on knowing how SUPER will affect them and, at the same time, how it will be affected by their ideas and concerns.
Then, the values and needs of the stakeholders were identified and translated into a values pyramid. We wanted to create a value-sensitive design for SUPER to meet our users’ needs successfully. These collected values have reshaped our platform and guided us through every step of our journey.

Issue Identification

It’s heartbreaking to know that autoimmune diseases continue to be a major challenge, affecting one in ten people worldwide. Despite all the efforts of medical professionals, there is still no permanent cure for autoimmune disorders. Instead, treatments mainly consist of immunosuppressants and immune-modulators that reduce overall immunity. One of these autoimmune and inflammatory diseases is Rheumatoid Arthritis (RA), in which our immune system mistakenly attacks healthy cells in our body, causing inflammation in the affected areas. RA primarily affects the joints, often attacking multiple joints at once. Sadly, RA has been the primary complaint of many people for a very long time. According to the WHO, an estimated 18 million people worldwide are living with RA. It is also a related cause of working disabilities and people quitting their jobs.
While treatments for RA have been developing and emerging in the past decades, it’s important to note that the patient’s condition is incurable. Patients must adhere to their treatment plan for the rest of their lives, which can be challenging as the drugs often cause various side effects. For instance, corticosteroids commonly cause lowered immunity, leaving the patient more vulnerable to infections, as well as hypertension, weight gain, and mood swings. Analgesics can cause permanent damage to the kidneys with long-term use, while DMARDs make patients more vulnerable to infections and can cause a rash and abdominal pain. This is why we chose to create a device that could one day develop into a complete cure for RA.

Stakeholders

Stakeholders Identification:

After identifying our problem, we held many brainstorming sessions to come up with a complete list of stakeholders. In these sessions, we got back to the roots of the word “stakeholder” to get a broader understanding of all its meanings. So we found that all the individuals, groups, or organizations impacted by the outcome of a project or having an impact on the project itself are considered stakeholders.
This has helped us identify relevant stakeholders in four different fields. These different fields constantly interact together and also interact with SUPER which builds the “bigger picture” of the whole project. In the following diagram, each sector contains the relevant stakeholders that we categorized based on our perception of their values and needs. For this step, we were inspired by the iGEM TU Eindhoven 2022 team, who provided a tool that helps get a clear overview of all the stakeholders and their relation to the project. Click on each of the upcoming buttons to see who these stakeholders are, why we integrated them into our project, and the values issued from them.

Stakeholders Sectors:

The industry consists of pharmaceutical companies and suppliers that have expertise in the development and marketing of new therapeutic devices.
Who?

We contacted two very well-established pharmaceutical companies through their delegates. The first was the famous international company Pfizer, represented by Dr. Ahmed ElShazly, the general manager of Pfizer in Egypt. We met Dr. ElShazly at the Africa Health ExCon, where we had the chance to declare our intentions to serve huge pharmaceutical corporations such as Pfizer as our primary customers. The second company was a local one, as we had a meeting with Dr. Yasser Farghaly, the CEO of Kahira Pharmaceuticals & Chemical Industries company. This meeting helped us reshape the course of our Integrated Human Practices.

Why?

These pharmaceutical companies could be the potential customers of our new platform SUPER. In addition, these huge corporations have wide expertise in the drug development process and the use of Mesenchymal Stem Cell-based therapy. On the other hand, these experts could enlighten us about all the essential laws and regulations regarding cell therapy and the related safety issues. Finally, meeting these experienced pharmacists approved that our project has successfully achieved the goals of SDGs number #3, #8 and #9, mentioned in our SDGs page.

Values:

Safety, Beneficence, Innovation, Quality.

Healthcare

Healthcare consists of all the hospitals that we visited and all the doctors and healthcare givers that we met along our journey.
Who?

In our Human Practice, we visited many hospitals like Maadi and Agouza, where we had the chance to meet Rheumatoid Arthritis (RA) patients, talk to their healthcare givers about their chief complaints, and discuss our platform SUPER with experts in Immunology and Rheumatology in both hospitals. We also had many meetings with a great collection of doctors from all over the world to discuss the kinetics of our device through the different stages of our project. These interviews can be found in detail on the Integrated Human Practices page.

Why?

Our visits and meetings made a great contribution to reshaping our project since its early beginning. Identifying patients’ needs and getting feedback from experts were both our guides in the development of our platform SUPER. Furthermore, the doctors helped us overcome many scientific and technical obstacles that we faced in the different steps of our project.

Values:

Public Health, Beneficence, Quality.

Government

The government sector is represented in the Egyptian Health Insurance along with the attorneys and the lawyers that represent the Egyptian laws and regulations concerning drug development.

Who?

In the Africa Health ExCon, we had the chance to meet one of the Egyptian Health Insurance representatives who gave us a lot of information regarding our insurance program and the patient’s needs in our society. Moreover, it was critical to contact an experienced lawyer in the pharmaceutical sector and patent law. Hence, we arranged a meeting with Mr. Amr Kirshah who is a lawyer and patent attorney at Kirshah IP.

Why?

These meetings helped us better understand the healthcare system and anticipate the impact of our platform SUPER on patients suffering from RA. In addition, we managed to comprehend the laws and regulations needed for the patency of our intellectual property.

Values:

Public Health, Communication, Justice.

Patients

Patients who are diagnosed or at high risk for RA.

Who?

All the patients that we met in our hospital visits and all the high-risk workers that we encountered in our field visits.

Why?

Patients are considered the most important stakeholders because all the essential values and needs are issued from them, and they are the first to be influenced by our platform SUPER. Hence, their safety and well-being were always our absolute priority. Adding to that, their feedback and concerns are the essential shaping tools of our device.

Values:

Safety, Communication, Quality, Public Health.

Stakeholder Analysis:

A Power-Impact Matrix is used to categorize all the stakeholders relevant to our platform based on the degree of impact of SUPER on them. Hence, in the following diagram, stakeholders are grouped based on Power (the ability to influence our project) and Impact (the effect our project has on them). An action plan is employed to deal with the stakeholders of every quadrant.

High power, highly impacted people:

For the stakeholders in this quadrant, we should manage them closely. Hence, we tried to engage them in every step of our project through regular meetings and keeping them constantly updated with our progress.

High power, less impacted people:

The goal for the stakeholders of this quadrant is to always meet their needs. In other words, we try to keep them satisfied by having occasional meetings to keep them informed about the big developmental steps in our project.

Low Power, highly impacted people:

The stakeholders who lack power but are highly influenced by our platform must be kept informed throughout our project. Therefore, we tried to keep in contact with them and update them on our progress to gain their trust and keep their high hopes.

Low power, less impacted people:

The stakeholders of this quadrant are only monitored along the course of our project. We contact them only if we need some expertise in a specific field or on a specific topic.

Value Sensitive Approach

1) Safety:

One of the most important topics addressed by our team and all the people we recognize as our project stakeholders. By gathering the data from our surveys and from the Africa ExCon conference feedback, we found that people have concerns regarding cell therapy safety assuming that it could suppress the immunity as a whole and its full side effects aren’t yet discovered. As a response to these concerns, we optimized our drug’s proof of concept to be as safe as possible. In addition, we went on looking for the challenges that could face the safety of our patients in order to overcome them. Hence, we found that the WHO has set the strategic framework of the global patient safety challenge to depict the four domains of the challenge: patients and the public, healthcare professionals, medicine, and systems and practices of medication. The framework describes each domain through four subdomains. This framework demonstrates how crucial it is for the finished product and the production process to be safe from the start of production until reaching patient treatment. This value has come up frequently in discussions with numerous stakeholders from various industries. We learned a lot about how to safely produce drugs via the CGMP (Current Good ManufacturingPractices) process. CGMP establishes methods to ensure the proper design, monitoring, and control of manufacturing processes and facilities. Adherence to CGMP laws ensures the identity, strength, quality, and purity of drug products by forcing medicine producers to control manufacturing activities appropriately.

2) Beneficence:

With this value in mind, it is important to maximize the benefits that our drug can provide compared to other treatments available. Our medication is designed to provide a one-time injection, removing the need to rely on other medications with potential side effects for years. By doing so, we can ensure that the patient experiences relief from their pain and minimize the risk of further damage to their joints.

3) Justice:

We are dedicated to bringing equity to the people, especially those suffering from RA. Unfortunately, due to the high cost of technology and production, the price of our drug may not be affordable to all patients. However, we firmly believe that every patient must have access to our drug, as it is a matter of need. To ensure that our drug is accessible to all patients, we have been in talks with governments and health insurance companies. We have proposed that they cover the expenses of our drug, or at least partially cover them. We recently discussed with a health insurance company agent and a representative from the Ministry of Health at the Africa Health ExCon. We wanted to know what steps are necessary for our drug to be covered and made accessible to all patients in need.

4) Autonomy:

It’s important to mention that patients have the right to make informed decisions about their medical care. This principle of autonomy is a fundamental aspect of healthcare, and it means that healthcare providers must seek the patient's consent or informed agreement before any treatment or investigation is carried out. This ensures that patients are fully aware of the potential outcomes, benefits, and risks of any medical intervention and that they have the power to make decisions about their health. By respecting autonomy, healthcare providers can ensure that patients receive the best possible care tailored to their unique needs and circumstances. Our responsibility is to ensure that the doctors are informed of the advantages and disadvantages of our medication so that they can openly discuss them with the patient before administration.

4) Innovation:

“SUPER” drug is entirely innovative since our approach involved integrating cell-based therapy with mRNA-based therapy to prevent the immune system from attacking the patients' joints and causing damage. Moreover, ethical considerations are always at the forefront of our research and we ensure that new technologies and discoveries do not perpetuate or create new inequalities. We firmly believe that innovation in ethics is essential to advance medical research responsibly.

5) Privacy:

Throughout our investigation, our team was exceptionally mindful of our patients' confidentiality. We recognized the need to preserve all patient data, which was critical to us. Our project included clinical research as well as surveys, and we made certain that all parties involved, including the general public, were kept informed and handled with dignity throughout the process. This enabled us to create a meaningful and ethical project that met the highest professional standards.

6) Public Health:

As we move forward with our project, we remain committed to upholding the principles of public health. We must prioritize the prevention of disease, the promotion of health, and the prolongation of life through organized efforts and informed choices made by individuals, communities, and organizations, both public and private. Our recent meeting with Dr. Mona Foad reinforced the importance of this approach. We learned about the impact of ergonomics on work-related disabilities and how rheumatoid arthritis is one of the leading causes of such disabilities. We must find a cure for this disease to decrease the burden on individuals and society as a whole.

7) Profitability:

As human beings, we all have the right to enjoy good health. This right is not just a mere luxury, but it is a fundamental human right that is recognized worldwide. The right to health is just one of the many other human rights that we should all be entitled to. It is important to note that the right to health is dependent on the realization of other human rights such as access to food, housing, work, education, information, and participation. Therefore, it is important to work towards achieving all human rights in order to ensure that everyone can enjoy good health. We have worked hard to offer our drug "SUPER" at an affordable price that can be accessible to all those in need. We understand that the cost may be considered expensive by some, but this is due to the high cost of cell therapy technology and materials. In our next steps going forward, we will seek alternatives that are cheaper and more affordable. Our focus is not on profit but on the importance of validating our proof of concept. We believe that everyone should have access to life-saving treatments, and we will continue to work towards that goal.

Africa Health ExCon

The Africa Health ExCon is one of the largest events held annually in Egypt. It includes a huge gathering of the world’s largest companies in the field of health and drug production. This year, the event was attended by 43,500 attendees, 75 counties, 368 exhibitors, and 2000 potential buyers.

The presentation of our project in such an event was a great opportunity to gather reflections that reshaped our project. Furthermore, attending the event provided us with a valuable chance to identify and meet possible stakeholders.
Thankfully, the conference organizers accepted our project proposal and offered us a booth in addition to a chance to pitch our startup in front of investors and entrepreneurs.
So, we kicked off by distributing ourselves on the booth explaining our idea to the people interested and hearing their feedback.

Interacting openly with people made us more aware of the impact of drugs on people's lives. After clarifying the preliminary prices of our proposed drug and therapy through our business model, people expressed their concerns about the expensive cost of using cell-based therapy in developing a treatment for Rheumatoid arthritis, which may reach up to 50,000$. This urged us to seek sponsorship and support through health insurance companies to increase the coverage of the treatment and reduce the net cost per employee suffering RA.
On the primordial version of our drug, we needed booster doses every period of time as we were targeting the use of engineered exosomes as the delivery system. Hence, one of the audience -who is an expert in the field of cell-based therapy- suggested using exosome-secreting cells as Mesenchymal Stem Cells to release our engineered exosomes. This would give us a sustainable source of exosomes while benefiting from its other immune regulatory functions.

Thus, extra-booster dosages would be unessential through the sustainable production of the therapeutic cargo-carrying exosomes released by our engineered Mesenchymal Stem Cells.
After that, we divided ourselves during the conference to target each critical stakeholder that could have an impact on our project.
To ensure that our technology is accessible to everyone who requires it, we have attempted to ensure that our product can be easily produced on a wider scale. Furthermore, we have contacted health insurance companies to determine what standards must be met before therapies can be covered by health insurance. Our long-term goal is to make our treatment affordable and covered by health insurance for any patient who requires it.
The second important concern mentioned by people was safety. Unsafe medication could cause harm or even death. The WHO has set The Strategic Framework of the Global Patient Safety Challenge depicts the four domains of the Challenge: patients and the public, health care professionals, medicines, and systems and practices of medication. The framework describes each domain through four subdomains.

This framework demonstrates how crucial it is for the finished product and the production process to be safe from the start of production all the way through patient treatment. This value has come up frequently in discussions with numerous stakeholders from various industries.
We learned a lot about how to safely produce drugs via the CGMP (Current Good Manufacturing Practices) process. CGMP establishes methods to ensure the proper design, monitoring, and control of manufacturing processes and facilities. Adherence to CGMP laws ensures the identity, strength, quality, and purity of drug products by forcing medicine producers to control manufacturing activities appropriately.

We thought about reaching out to representatives of the pharmaceutical and drug-developing companies to explore the best option of the cell-based therapies and estimate the cost of the MSC-based therapy compared to other choices like CAR-T-cell-based therapy and DC-based therapy.
We later met Dr. Ahmed Elshazly, the general manager of Pfizer in Egypt. We discussed our strategy and future business plans with him, as we intend to serve huge pharmaceutical corporations such as Pfizer as our primary customers
He praised our concept and stated that the Rheumatoid Arthritis market is massive and growing rapidly and that all we need right now are grants and funding to complete the project proof of concept in the lab, after which pharmaceutical companies could adopt our drug and move it through all of the drug manufacturing phases.

Finally, we pitched our project in front of a large audience of entrepreneurs, investors, and people interested in our project.

Among these investors were LYNX Strategic Business Advisors who admired our idea and offered to help us with the business model and the market analysis of our project this year.

Agouza Rehab Center

This year, the AFCM iGEM team had the opportunity to visit Agouza Rehab Center, one of the most well-known centers for the treatment of Rheumatoid Arthritis. It is well known for its knowledgeable medical personnel, top-notch service, and accessibility to rehabilitation facilities.
We required additional information to help us understand the patient's journey throughout the disease and to have a better understanding of the patient's perspective on our project. Moreover, when making decisions about health care procedures, the patient must have autonomy of thinking, significance, and action. As a result, the decision-making process must be free of influence or persuasion. A patient must understand all risks and benefits of the procedure, as well as the possibility of success or failure, in order to make an informed decision.
To do this, we entered the center, handed out surveys, and conducted in-depth interviews with patients. The surveys covered a wide range of issues, beginning with the patient's diagnosis and knowledge of the illness before he became ill and progressing through the degree of work disability brought on by the disease. However, our main objective was to concentrate more on the patient's preferred and used medications as well as whether or not he could take a medication developed using synthetic biology and cell therapy techniques. Also, we have to mention that these surveys were approved by the IRB in our college and by the ethical committee of the center itself.

We gave a brief, understandable explanation of the disease's pathogenesis. “it is an autoimmune condition in which the patient's immune system attacks his joints”, then we explained our strategy to the patients, in which we will train modified stem cells to suppress the immune cells responsible for attacking the joints and causing pain. Finally, we explained the method by which our treatment will function, using the plasma injection technique as an example. To block the cells from attacking the joints, blood will be drawn from the patient, immune cells are going to be modified, and then reinjected back into the patient.
The visit was critical because it allowed us to gain a deeper understanding of the patient's journey, how they could respond to a new medication, and what might persuade them to try a new drug to treat their medical condition. Furthermore, the findings revealed that patients were concerned about the possibility of their immune systems being damaged by the injected cells. As a result, we explained our strategies to make the treatment specific only for the disease immune cells and we are still employing safe elements in order not to affect the immune response and effectiveness of the patient's normal immune system.

Maadi Hospital

One of the largest hospitals in Cairo is Maadi Hospital. Every day, thousands of patients come in for treatment, and the rheumatoid department receives hundreds of patients for their regular follow-up.
We decided to gain more knowledge about the prevalence of the condition, the frequency with which people visit their doctors, the medications prescribed to them, how well the patients adhere to their therapy, and lastly, the physicians' feedback on our drug.
We began by conducting in-depth interviews before giving the doctors surveys to fill out in order to gather data. We were able to describe the patient's journey thanks to this knowledge more clearly.

When the patient first complained of symptoms, we inquired whether the condition was at an early or late stage. the patient's awareness of the illness before symptoms appear.
The doctors addressed the most common problem that all patients have, which is that they believe their joint pain is caused by activity or simply joint inflammation, leading them to use over-the-counter painkillers that mask the pain but do not stop subsequent joint deterioration.
Then they added that one more factor contributing to the patient's joint deterioration is the weak adherence to the treatment due to several factors, the most important of which is its high cost, even though health insurance companies partially cover it. Another factor is due to the drugs' side effects and the fact that they must be taken for the rest of their lives making the patient think that the disease is incurable and it is life-long lasting.
Finally, we explained that the SUPER platform -established by our team- is personalized for every patient as it will be modular and can be tuned by the activity of the Syn-notch receptor mediated by the number of autoreactive B-cells in the environment. Also, the response and the levels of our therapeutic agent will be variable in each patient according to the condition and severity of the disease. Thus, this will diminish the possibility of complications from the disease and multiple organ damage due to improper management of the patient’s condition. In addition to controlling the cycles of relapse and progression phases that are poorly managed by the current modalities of treatment.
The physicians warmly welcomed the idea and emphasized that such an idea would revolutionize the field of autoimmune therapy by relieving the patient's health and financial burdens associated with taking immunosuppressive medications for the remainder of his life.

Questionnaires

Rheumatoid arthritis is an autoimmune and a common inflammatory chronic disease. It consists of a syndrome of pain, stiffness, and symmetrical inflammation of the synovial membrane (synovitis) of freely moveable joints.
It is known that RA is one of the most prevalent diseases in Egypt, but we have to know for ourselves how much this disease affects Egyptians from laborers in the working age to the elderly.
This is why we decided to head to different hospitals such as Maadi Military Hospital, Rehabilitation centers like Agouza Military Rehabilitation Centre, and also various construction sites.
Among these different places, we had the chance to meet many patients to whom we distributed our questionnaires. This has helped us measure the true epidemiology of RA and discover the broad-based characteristics of this disease among the Egyptian population. It is also important to mention that this questionnaire was validated by the IRB board of our college thanks to our meeting with Dr. Wagida.
The total population that answered our questionnaire was 151 persons. The analysis of the provided data resulted in the following outcomes:

The population of males who answered our questionnaire was larger than females, due to the male domination of the strong occupations which depend mainly on operating heavy equipment. However, RA diagnosis among females was larger with a ratio of 3:1.

We also found out that the level of education of our sample was strongly related to the prevalence of the disease. In other words, RA affects those with a lower educational level due to their lack of knowledge about the risk factors and different preventive measures of such a devastating disease.

This increases the burden on our team and highlights our important role as medical students and researchers to enlighten those patients and spread awareness about this epidemiologic disease.
We were also keen on identifying the main physical complaints of RA patients in Egypt. Hence, we found the following:

After collecting the personal data, we started asking the RA patients about their personal feelings and the lifestyle changes due to RA.
Do you think RA has changed your lifestyle?
This is one of the most important questions in our survey because RA is not just another disease that a patient can live normally with. Most patients encounter severe changes in their lifestyle due to the handicapping effect on the different aspects of life of RA.
As expected, the answer to the above question was 88% ‘yes’, while the rest of the patients -especially the construction laborers- refused to give up on the fact that this disease has negatively affected their professional lives in one way or another.

In the final stage of our questionnaire, we wanted to gather more accurate information about the current treatment options for RA in Egypt. So, we asked the patients about the drugs they take, and we came out with the following chart:

It was evident that the most frequently used treatment options (Methotrexate, Steroids, Painkillers…) only aim to relieve the inflammation and ease the pain in the joints. Therefore, we decided to introduce our new drug idea to the patients to test their acceptance of such a novel therapeutic approach.
But before that, we had to make sure that our patients were well-informed about Stem Cell-based therapy. Then, we started simply explaining our novel platform and we answered all their questions concerning the side effects, the route of administration, and the expected dose.
Finally, we asked our patients about their intention to try Stem Cell-based therapy. The answer is reflected in the following chart:

Fortunately, our therapeutic approach has gained the acceptance of most patients who want to try this new kind of medicine whenever it gets to the market. A lot of these patients even believed that our idea could represent a breakthrough in the treatment of RA.
Thanks to this questionnaire, we now have collected all the data that we need to start implementing our project in real life. We have gained the trust and raised the hope of many suffering patients, and we cannot let them down. The responsibility is getting bigger, but our passion and our dedication will always remain our guide in this battle against RA.

Introduction to integrated human practices

In the Integrated Human Practices of this year, we aimed to engage as many relevant stakeholders as possible. This is why we contacted experts and professors in many different fields related to our project. Then, we reflected upon every feedback and every criticism issued from these stakeholders, as we wanted to optimize our device SUPER in order to become the most feasible, effective and successful solution for Rheumatoid Arthritis (RA).
At the same time, we were aware that the development of any new technology is never all about researchers and engineers. We must have constant contact with the people who are influenced the most by this invention. Hence, these people could improve and reshape our design based on their needs and values. This value-sensitive approach could consequently help us make a great impact on the lives of those who are suffering.
Thanks to all our visits, interviews and meetings throughout the year, we created a large database for our project where we grouped all the different perspectives of the stakeholders. Next, all these reflections were implemented and integrated to pave the path for the development of our device SUPER. This integration is represented throughout our Interactive Timeline where we tell the story of our design with all our setbacks and our victories, arriving at our final complete approach.
However, if you want access to our ordinary Integrated Human Practices page, press this link.
We wanted to tell this long story in the simplest way possible. Therefore, we divided our Integrated Human Practices into five consecutive stages represented by our Interactive Timeline. The first stage is the Motivation where we reveal our main source of passion and dedication which kept us going all along the journey. Next comes the Research and Thesis stage where we gathered tons of information about the epidemiology, the pathophysiology and the regular management of RA. Then, it was time to check the feasibility and the laws regulating different types of cell-based therapy in the Ethical Background stage. After that, we explain all the milestones of our design with all the integrated modifications suggested by our stakeholders. This stage is called the Development. Finally, we show how our project started to take small steps into the real world as a true feasible drug in the Lab To Market stage. This final stage is considered a starting point for our Entrepreneurship work.