Figure 1. AREA framework
Figure 2. Stakeholder classification
Human Practice Framework
Tackling the issue of cancer is no small feat. If we want to solve this problem genuinely, we need to approach it from a human-centered perspective. Modern medicine has proven that no disease, not even cancer, is a simple act. It is the unfortunate culmination of various risk factors. Genetic inheritance is certain, but habits, economic status, access to healthcare and health facilities, as eco-social factors also play part in determining the health and wellbeing of people (1). Thus, we are not only taking into consideration the perspective of company and governmental stakeholders but also the family of patients themselves, the experts and scientists, and the healthcare workers who have been on the frontline of this fight. To best showcase this, we will be using UKRI’s AREA framework (2) to show how we take advice and insights from our stakeholders: Medical Doctor, Experts, Public Health Institutions, Scientists/Researchers, and Family of Patient.
Anticipate:
We looked at the current situation on the prevalence of colorectal cancer and the ongoing research surrounding it to gauge what impact would our research and its outcome have. We talked with a representative from the Ministry of Health of the Republic of Indonesia to align our understanding and vision on a national level and also the local District Health Office. This allows us to gain both the overall and regional understanding of the problem. We learnt that despite governmental efforts in Primary Healthcare Facilities, there are still many at-risk patients who are unable to feasibly access them for various reasons, from geographical hurdles to socioeconomic factors. We are also reminded of how crucial the user experience and convenience is for the average public to widely adopt new technologies and design.
Reflect:
We reflect back at our plans and findings, evaluating how our work will impact communities and stakeholders in this field. Looking back to our conversations with healthcare officials and family of patient, we decided to focus on easy-to-use screening tools that utilize synthetic biology to allow greater access for rural communities. A lot of patients in rural areas work in informal sectors. This means for most of them, they cannot afford spending a whole day going to healthcare facilities for a screening test as that could mean an entire day without income or even food. A device that can be used anywhere and anytime without much required infrastructure or technology to store and use can open wide the access bottleneck the civilians in rural areas are facing.
Engage:
In this period we introduce our ideas to various people from different perspectives representing different stakeholders. We set up meetings and educational programs, inviting both the academia and lay people to take a look at our ongoing project and to exchange beneficial knowledge. We met with villagers from Sleman, Yogyakarta who showed concern about the disease as well as interest in our project. From them we gleaned the priorities of the possible patients that will be our end-users in regards to their desired outcome and experience, and we made sure to take note of it in further refining our practical ideas. Through these opportunities, we also made contact with some biotechnological institutions, including a collaborator of the Ministry’s precision medicine initiative, and the National Food and Drug Monitoring Agency. They pointed out our technical mistakes and guided us to possible pitfalls and problems we should be mindful of when we scale up our research. We also held a webinar with iGEM UI and LiEW STRATEGiCS/ENZYMiCS, presenting both of our researches and teaching the role of biotechnology in health to university students in Indonesia, who showed great interest. Multiple lectures were also done to multilevel students: pre-schoolers, elementary schoolers, high schoolers, and college students; bringing topics not only limited to colorectal cancer but also on synthetic biology, genetics, the digestive system, and biology, through interactive ways. We also held an engaging lecture in a rural area to increase people's knowledge and awareness on the importance of screening for colorectal cancer, where they could directly ask us any questions in the realm in mind. Ensuring anyone and anywhere could receive the education we want to deliver, we also participated in a radio program. Lastly, having peers with the same experience encouraging us is very impactful in giving reassurance when facing struggles in life, thus we collaborated with iGEM Patras to disseminate a motivational video on social media for cancer patients, by cancer patients and a comic book about cancer translated into Indonesian. We also partnered with NYCU-Taipei iGEM to hold the Synthetic Biology and Diagnosis Seminar.
Act:
All of these insights and guidance would mean nothing if we do not act on it. After collecting all the concerns, suggestions, and criticisms from all the stakeholders we contacted, we analyzed them to highlight the core issues they have. We continuously update our designs and plans based on their inputs and feedback. Through this we make sure that their interests and priorities align with us and our end-product could satisfy their expectations. In the end, we also concocted a proposed implementation plan, containing aspirations on how we will act upon the execution of our project into the public.
https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC9578089/
https://www.ukri.org/who-we-are/epsrc/our-policies-and-standards/framework-for-responsible-innovation/
Introduction
It is compulsory for us to verify our claims and get answers to our queries through conducting interviews with stakeholders aligned to the realization of ColDBlu. Hereby, we contacted and consulted to several stakeholders, including the family of a patient and experts in the medical, healthcare, pharmaceutical, and biotechnological fields, who each voiced their concerns and advice on our innovation. With the best of our efforts, we managed to find and integrate the solutions to the concerns as well as the recommendations for the greater development of ColDBlu as a novel, cutting-edge GMO probiotic product.
The Underlying Problems (Literature Review)
Figure 3. Cancer prevalence per province in Indonesia in 2013-2018 (1)
Based on the 2018 Riskesdas (Riset Kesehatan Dasar/Basic Health Research) results from the Ministry of Health of the Republic of Indonesia shown above, the Province of Yogyakarta has the highest number of cancer cases in Indonesia. The prevalence of cancer in the Province of Yogyakarta is three times higher than the overall prevalence of cancer data in Indonesia, which is 4.9 per 1000 population (1). This indicates that cancer cases in the Province of Yogyakarta need to be addressed promptly. According to the distribution map of cancer cases in Yogyakarta in 2022, the average age of cancer patients is 55.08 ± 15.46 years. The most commonly diagnosed types of cancer are breast cancer, cervical cancer, and colorectal cancer. Most cancer patients come from the Sleman Regency and economically poor areas, with one of the factors influencing the high number of cancer cases being the low and limited cancer screening rates (2). Therefore, the efforts to improve access to cancer screening and raise public awareness about the importance of early cancer detection are crucial in addressing this issue in the Province of Yogyakarta, as well as other parts of the world.
Colorectal cancer (CRC) is the third most prevalent malignancy and the second leading cause of cancer death worldwide, with the Asian population ranking first in terms of the incidence and mortality (3). From Jogja Cancer Registry’s data for 2022, CRC cases were dominated by males which is 54%, adults of productive age (20-69 years) which is 62.3%, and advanced tumors which is 49.7% (4). Despite the slow progression of CRC, taking approximately 10-15 years, a majority of CRC patients in Yogyakarta are diagnosed at advanced stages due to the difficulties in diagnosis. Furthermore, early diagnosis plays a crucial role in determining the success of therapy. Consequently, routine CRC screening is highly recommended as it can detect CRC at an early stage, reducing the incidence and mortality rates of CRC (5).
Current CRC detection methods encompass a range of approaches. Endoscopic procedures, such as colonoscopy, are invasive, require bowel preparation and sedation, and carry a small risk of complications like bleeding or perforation. Non-invasive stool tests, like the fecal occult blood test (FOBT) and fecal immunochemical test (FIT), do not directly detect cancer, and false positives and negatives can occur (6). Stool DNA tests, such as Cologuard, have a higher false positive rate and are more expensive than other stool tests. Imaging procedures, like virtual colonoscopy utilizing CT scans, still require bowel preparation, carry a risk of false positives, and involve radiation exposure. Blood tests, such as measuring tumor markers, lack specificity to colorectal cancer and are not recommended as primary screening tools. In conclusion, there’s a need for a new method of CRC screening that is non-invasive with high sensitivity and specificity.
Furthermore, we are aiming to develop an affordable and minimally-invasive early screening test of colorectal cancer (CRC), especially in rural areas as they face unique challenges in implementing and accessing CRC screening services. One of the most important aspects is limited education or awareness, contributing to a lack of understanding about risk factors, preventive measures, and the availability of CRC screening services. Rural areas are also characterized by dispersed populations and long distances to healthcare facilities, leading to reduced access to screening centers, making it difficult for residents to undergo regular CRC screenings. Not to mention rural populations frequently experience lower socioeconomic status, which can impede access to healthcare resources. Factors such as limited health insurance coverage, financial constraints, and high out-of-pocket costs for screening tests can prevent individuals from seeking preventive care services. Lastly, rural regions often face a shortage of healthcare providers, including gastroenterologists and primary care physicians, resulting in longer wait times and delays in diagnosis for patients residing in rural areas. The mentioned challenges above indicate that, in addition to the need for non-invasive CRC screening methods with high sensitivity and specificity, it is equally imperative to consider additional factors, such as ease of use, cost-effectiveness, and the elimination of the requirement for healthcare providers intervention, for a better CRC screening method in rural areas. The implementation of our project into the wider-scope of people was also still quite an enigma for us.
For all these reasons, we hold the mission within our Human Practices vision to connect and engage with various stakeholders and potentially-affected parties to share our insights with them as well as relay queries that we were still in doubt about and need further evidence, confirmation, and information. Having dialogues with these people would allow us to obtain and retain a better understanding of the puzzle we are trying to solve with ColDBlu.
Figure 4. Stakeholder interview chronological flowchart
Stakeholders’ Concerns (Interview Results + Documentation)
1. PathGen Diagnostik Teknologi (1 April 2023)
Profile:
Being a health biotechnology company in precision medicine that provides low-cost and robust molecular diagnostic tools; PathGen’s vision and mission resonate with the strive of our project, which is to allow the access of affordable, accurate, and safe screening tool for colorectal cancer patients.
Purpose:
We had a discussion with PathGen CEO Dr. Susanti to inquire about the stakeholders that we need to consult with; the aspects of our project that still need to be heeded; and any advice that the CEO could give us based on her own knowledge and experience of researching and founding a similar innovation.
Contribution:
Dr. Susanti instructed us to ensure the scalability of our plasmid construct and the technology readiness level (TRL) of our overall innovation. She also told us to carefully check whether the plasmid conforms to GMO regulations. The concept is reasonable and plausible, however the execution still needs to show how deliverable and possible it is. She advised us to look up similar start-ups as benchmarks. She looks forward to the development of our project into a colorectal screening company, similar to what she has accomplished. For this to be realized, we are suggested to actively seek potential business investors who can help elevate our project's TRL to the next level. Despite business implications and investor interventions, it is ultimately crucial to hold on tightly to the scientific and clinical regulations and ethics. Lastly, PathGen is very open to providing any experts and facilities beneficial to the implementation of our project.
How Did We Integrate the Inputs?
We figured out how to construct the right plasmid design, which is through inserting our detector segment, namely LIRA (loop-initiated RNA activator), and reporter segment, namely aeBlue chromoprotein gene, into an endogenous plasmid of EcN, namely pMUT1, hence the recombinant plasmid can be more stable in EcN from one generation to the next generations.
We confirmed the conformity of our project to existing GMO regulations and whether the execution of our project is realistic, feasible, and deliverable to BPOM RI (Badan Pengawas Obat dan Makanan Republik Indonesia), or the Food and Drug Supervisory Agency of the Republic of Indonesia, who are the highly knowledgeable experts in the area of food and drug safety regulations and management.
Corresponding to the TRL level of our project, we indeed realize how vital scalability is thus we did a self-assessment indicating that our current phase aligns with the preliminary study stage, which corresponds to TRL levels 3 or 4, and our goal is to advance to level 5 and successfully pass the “Valley of Death” in technology development by finding the appropriate investor.
2. Ministry of Health of the Republic of Indonesian (Kementerian Kesehatan Republik Indonesia (Kemenkes RI)) (23 March 2023)
Profile:
As the topmost body that governs public health in Indonesia, the Ministry of Health oversees various policies for surveillance and prevention of disease, including for cancer. To tackle as big of a problem as cancer in Indonesia, it would be unwise for us not to consult them for their insights.
Purpose:
We approached Roy Himawan, S.Farm., Apt., M.K.M, the Director of Pharmaceutical and Medical Devices Resilience, to gain greater insights on the condition of colorectal cancer in Indonesia as well as aligning our goals and project to national needs and interests.
Contribution:
Mr. Roy shared that colorectal cancer is currently one of the greatest problems faced in Indonesian Public Health. CRC has the second largest mortality rate among other cancers in the Indonesian male population and has been listed as one of the diseases targeted by the Ministry of Health’s “Health Transformation” program to be tackled in the current regime. Routine screening is still a big hurdle, as most of the population, for various reasons, could not afford to go for routine screening. A simple screening method that is done at home would be helpful. After COVID, a lot of PHC (public health centers) already have PCR machines, but it is not yet universal. Molecular screening is considered but is still difficult. Last but not least, government support in Health Transformation is eager to pursue novel methods in molecular & genetic testing, and welcome any and all attempts of collaboration. Additionally, he advised us to reach the Indonesian Food and Drug Monitoring Agency for the detailed steps we need to do to register our product.
How Did We Integrate the Inputs?
We now have a clearer vision over the current condition of CRC in Indonesia right now, and how it is indeed a national health concern that is shared with the Indonesian government. This convinces us that we are indeed on the right track and that our research outcome would improve the lives of many Indonesians.
The Ministry of Health showed great interest in our endeavors and expressed their support for our research. They shared with us the current focus of the Ministry of Health in the field of precision genetic medicine and invited us to further develop our research under this framework and collaboration. Through this, we gained channels to other researchers and stakeholders that are also involved in the field for consultation.
Thanks to the insight and discussion with the Ministry of Health, we now have a clear path and direction to take our research further. This inspires us to make sure the product of our research could be cheaper, more inclusive, and more accessible to answer the problem of CRC that currently exists in Indonesia. We strive to be the next state-of-the-art provider for screening tools with partnership to the government. We also need to reach the Indonesian Food and Drug Monitoring Agency for the detailed steps we need to do to register our product.
3. Medical Doctor (13 April 2023)
Profile
Prof. Gunadi, MD, Ph.D, Sp.BA., Subsp.D.A(K) is one of the leading geneticists, doctors, and surgeons in Indonesia. He currently serves as the president of Indonesian Society of Human Genetics and the leader of the Sardjito General Hospital branch of the newly launched Biomedical and Genome Science Initiative (BGSi) by the Ministry of Health of the Republic of Indonesia. His experience in the field of human genetics is unquestioned, and being both a geneticist and medical doctor, he possesses the rare perspective and understanding that combines the two fields.
Purpose
We consulted with him to ask his expert opinion on our design’s scientific concept and making sure that it is sound. We also asked his opinion from a medical doctor perspective over possible concerns and issues that may rise in practice when our project is implemented. Lastly, we discussed the possibility of future collaborations with the government’s BGSi program and other genomic medicine projects in Indonesia.
Contribution
We extended a discussion with him on the mechanism of our biodevice as well as the medical basic science behind it. He confirmed our decision on targeting miRNA 21 as a screening/diagnostic marker, and he gave guidance regarding our plan as the RNA might also be falsely present in other pathologic conditions. Prof. Gunadi reminded us that while currently liquid biopsy methods are still uncommon and largely inaccessible in Indonesia, it might change in the near future as the government is currently focused on expanding precision medicine technology in Indonesia. As such, he suggested that we distinguish our design with some other advantages. Lastly, he gladly invited us to participate in future research with Sardjito General Hospital in the field of genetic medicine and open up potential for collaborations with us and our project in the future.
How Did We Integrate the Inputs?
In the search of other advantages that our project provides, we designed our project to be more affordable than laboratory based genomic and transcriptomic examinations, on top of being more accessible to both practitioners and lay people, while still giving accurate and specific results.
4. National Research and Innovation Agency (Badan Riset dan Inovasi Nasional (BRIN)) of the Republic of Indonesia (15 April 2023)
Profile:
As one of the research institutes in Indonesia, the National Research and Innovation Agency or Badan Riset dan Inovasi Nasional (BRIN) also conducts research in the health sector. Therefore, as a research team, iGEM UGM needs to do a consultation with professional research institutions such as the National Research and Innovation Agency regarding the project we are working on, especially in terms of the methods and analysis.
Purpose:
We approached Maulida Mazaya, Ph.D. who works as a Young Computational Specialist Researcher in the National Research and Innovation Agency to consult about our simulation methods and analysis. Furthermore, we also inquired about collaboration opportunities that could be carried out between the iGEM UGM team and the National Research and Innovation Agency.
Contribution:
Ms. Maulida gave suggestions on how to make our research project’s results more stable by adding simulation methods, determining thresholds, and deepening the kinetic modeling by changing concentrations or comparing them. Until the next few years, the National Research and Innovation Agency focuses on the omics database rather than initial screening (it has not entered into the biological system). To wrap up our discussion, Ms. Maulida stated that it is possible to cooperate and collaborate together with the National Research and Innovation Agency in the future by submitting collaborations proposals or making open calls on collaborative grant proposals.
How Did We Integrate the Inputs?
Ms. Maulida from BRIN Introduced us to BGSi. BGSi or Biomedical and Genome Science Initiative is first National’s integrated biomedical initiative launched by the Minister of Health of the Republic of Indonesia on August 14th 2022. We also utilize miRNA, which is also a genetic material. When BGSi becomes more widely-applicable, our project can collaborate together with the program hence upgrading its function to not only be limited to providing genomic data analysis but also linking them to diseases
5. Sleman District Health Office (Dinas Kesehatan (Dinkes) Sleman) (16 June 2023)
Profile:
We conducted a meeting with the Sleman District Health Office, a government institution dedicated to enhancing the well-being and quality of life of the population within the Sleman District. The interviews were done specifically with dr. Seruni Agreini Susila, MPH; dr. Khamidah Yuliati, MMR; and Kurnia Yuliawati, S.Si., Apt., MKM. The responsibilities of the Sleman District Health Office encompass improving the quality of healthcare services, implementing preventive measures and disease control, promoting community involvement in healthcare maintenance, and developing human resources within the healthcare sector. This is why we engaged in discussions with them to explore opportunities aimed at achieving these goals.
Purpose:
We approached the Sleman District Health Office aiming to collect data on colorectal cancer patients in order to understand age patterns, gender distribution, diagnosis stages, as well as the origin of patients from rural or urban areas. Additionally, we aspired to comprehend the programs and efforts that had been implemented by the Sleman Health Office and Community Health Centers in addressing colorectal cancer cases. This visit was also intended to assess the feasibility, procedures, and recommendations for the implementation of our innovative project in the community.
Contribution:
First of all, dr. Seruni suggested undertaking specific promotive efforts, such as disseminating educational and informational colorectal cancer leaflets. Moreover, it is essential to conduct awareness campaigns to elevate the community's understanding regarding the significance of screening. Both dr. Seruni and dr. Yuliati also conveyed the importance of the local community’s role in raising people’s awareness to undergo screening and about the disease itself. In closing, dr. Seruni and dr. Yuliati hope that a new screening technology can be manifested to capture a broader scope of the community, especially for individuals in their productive age who find it challenging to allocate leisure time to travel outside their homes and workplaces to do screenings. Through taking these measures, the decrease of colorectal cancer case prevalence and enhanced quality of life are expected to transpire. Accordingly, she spoke favorably of the collaboration possibility with District Health Offices in Indonesia for the implementation of our project’s early-stage screening technology. In addition, we also obtained data related to survivors provided by the Sleman Health Department, such as background, socioeconomic status, age, and cancer stages experienced, enabling us to strengthen the arguments underlying the creation of our project.
How Did We Integrate the Inputs?
We recognize the need for an approach to the community because awareness and education regarding the importance of colorectal cancer prevention and early screening are still insufficient. To enhance public awareness, we initiated the “iGEM Goes to Rural Areas” program to provide direct education on the prevention and significance of early screening for colorectal cancer. Additionally, we have also created and distributed leaflets to further raise awareness among individuals at risk of colorectal cancer, ensuring that the information we provide is more easily understood. Our product serves as a solution to assist health authorities by simplifying the process of reaching out to the community for screening, offering flexibility in its usage, and thus encompassing various segments of the population without being constrained by specific timeframes.
6. Indonesian Food and Drug Monitoring Agency (Badan Pengawasan Obat dan Makanan Republik Indonesia (BPOM RI)) (1 September 2023)
Profile:
The Indonesian Food and Drug Monitoring Agency (BPOM RI) plays a crucial role in ensuring the safety of drugs before their distribution to the public. We held a meeting with Sofhiani Dewi, STP, M.Si., Siti Maemunah, S.Farm, Apt., M.K.M., and Ati Widya Perana SP for an interview. The Indonesian Food and Drug Monitoring Agency (BPOM RI) is a government agency responsible for supervising and regulating drugs, food, cosmetics, and other health products in Indonesia. BPOM RI has a vital role in ensuring the safety, quality, and efficacy of these products, as well as protecting the public from potentially harmful health products.
Purpose:
We conducted an interview with The Food and Drug Administration of the Republic of Indonesia (BPOM RI) to determine if our project can materialize as an engineered medical device for detecting colorectal cancer. Additionally, we aim to understand the regulations that need to be met to commercialize our project in the community. We also wish to ascertain whether our product has the potential to serve as a screening tool for the general public.
Contribution:
Ms. Siti Maemunah provided us with advice to ensure whether our project falls into the category of genetically engineered food or not. Ms. Siti Maemunah observed that our product leans more towards pharmaceuticals due to its utilization of biotics as markers rather than genetically engineered food products. Furthermore, our product takes the form of capsules and serves as a diagnostic rather than therapeutic product, thus aligning more with non-food items. Therefore, she recommended that we reach out to the pharmaceutical division for further processing. Additionally, Ms. Siti Maemunah advised us to investigate the consumable dosage, as this significantly impacts the product's sustainability.
How Did We Integrate the Inputs?
After conducting our initial meeting with the Indonesian Food and Drug Monitoring Agency (BPOM RI), we made the decision to schedule a follow-up meeting with the pharmaceutical division, in the hopes of obtaining more relevant and detailed explanations. We did this with the aim of advancing the development of our product on a larger scale, thus preparing it for further commercialization processes. However, the pharmaceutical division informed us that it is not suitable for us to consult with them since our project innovation does not contain active ingredients thus incorporated as a medical device. This led them to recommend us to contact the Directorate General of Pharmaceutical and Medical Devices of the Ministry of Health of the Republic of Indonesia again.
7. Family of Patient (5 October 2023)
Profile
Ms. T (name initial; interviewee would like her identity to be concealed) was the wife of a colorectal cancer patient who unfortunately died back in 2017. Living in Jambearum Village of the Kendal Regency, which is still considered in the more-rural side, Ms. T was willing to share her viewpoint when accompanying his late husband throughout his journey fighting colorectal cancer, as a family of a colorectal cancer patient from a rural area. We believe that her perspective is pivotal for our ColDBlu project since it focuses on, especially, supporting colorectal cancer screening for people in rural areas.
Purpose
We interviewed Ms. T in order to ask her about her experience being the family of a colorectal cancer patient. We expected to learn about her standpoint for the criticism and flaws of the current healthcare system in (the rural areas of) Indonesia as well as take in her advices for the current healthcare system in (the rural areas of) Indonesia and our ColDBlu project.
Contribution
Through the conversation with Ms. T, we had the opportunity to perceive CRC through the lens of the affected. Ms. T and her late husband (the patient) were shocked when they first heard the diagnosis (i.e. the late husband did not undergo any form of (colorectal) cancer screening) that the disease the late husband had been dealing with for quite a long time turned out to be colorectal cancer. Ms. T’s late husband himself had a family history of cancer thus after getting the disease’s symptoms, the doctor warned them that there is a high possibility that what the late husband was facing was a form of cancer. When the symptoms first arose, Ms. T accompanied her late husband to visit a general practitioner at the local health center, of which then the late husband was directed to do a checkup at a district hospital as the facilities and resources at the local health center were not specialized enough. At the district hospital, the late husband finally did a CT scan and the result unfortunately already showed a high cancer stage. To be able to undergo the CT scan, the late husband had to wait for 2-4 weeks since the tool was broken at that time. After realizing the high stage, the district hospital doctor directed Ms. T and her late husband to a provincial hospital, which was located in another city (Semarang), 40 km away from their residential place. Up until the district hospital, Ms. T had to utilize out-of-pocket expenses and only managed to issue the National Health Insurance after having to move to the provincial-hospital level. In the provincial hospital, the late husband finally underwent a colonoscopy, which exhibited a result that the malignancy had spreaded towards the liver. Despite going through treatments for 8 months, Ms. T’s husband eventually died.
From this experience, Ms. T relayed that it was quite distressing that it took too long of a time for her late husband to be directed by the healthcare workers to receive diagnosis and treatments at the provincial hospital, which had more complete healthcare facilities and resources. It was when the disease had already been severe that the late husband was directed to the provincial hospital. Ms. T emphasized that the medical tools and healthcare workers in rural areas need to be optimized, also that giving education to the patient and the family of the patient is a vital point so that they know what decisions to make next. The reason why education is particularly important in rural areas is also because the culture there tends to encourage and lead patients to do medical checkups to informal village “clinics” as they are reluctant to take a leave of absence from work to visit proper medical doctors hence deciding to just visit these “clinics” that are near their homes. As a closing, Ms. T remarked that our ColDBlu project is a great solution as it can become an early indicator for CRC hence creating a sense of urgency in the patient to quickly undertake the next required medical procedures. As the ColDBlu pill can be taken straight-away from home, it also allows more flexibility for the patients.
8. Lecturer at the Faculty of Pharmacy
Profile
Ms.Dwi Endarti is one of the lecturers in the Faculty of Pharmacy, Universitas Gadjah Mada. Her research interests are in the area of pharmaco economics and health technology assessment, health-related quality of life measurement, and pharmacy management. She has published several articles related to her research interests in international journals. Ms. Dwi Endarti is also a member of ISPOR (International Society of Pharmacoeconomics and Outcome Research) since 2011. Since 2019, she became a member of the national committee of national formulary. Currently, she is the head of the Master Program in Pharmacy Management in Universitas Gadjah Mada.
Purpose
We approached Ms. Dwi to consult about the pharmacoeconomic aspect of our product and what we need to do to ensure our project could be scaled up into industry standard and potentially could be integrated with the national program of colorectal cancer screening.
Contribution
Ms. Dwi advised us that since our product will be focused on screening, we need to formulate the proposed price of our product and the outcome then compare it to the gold standard in Indonesia. However, according to the national disease management of colorectal cancer released by the Ministry of Health, there are currently no gold standard testing. Because of that, we compare our product with all the colorectal cancer tests available in the country including FOBT, FIT, Sigmoidoscopy, and Colonoscopy. To ensure valid data, our team needs to conduct a comprehensive literature review on the current testing methods.
How Did We Integrate the Inputs?
We gained insights to choose sensitivity and specificity as the parameters of colorectal cancer screening tests’ effectiveness to be studied in our pharmacoeconomic analysis. Since our research is currently in the preliminary study stage and the product cannot be made available in the meantime, we cannot measure utility outcomes such as quality-adjusted life years (QALY) which is widely used in pharmacoeconomic studies. Ms. Dwi reassured us that this is an understandable challenge in the development of new methods or interventions. However, sensitivity and specificity were also commonly utilized to demonstrate the effectiveness of screening tests. Therefore, we estimated the sensitivity and specificity of our product and other colorectal cancer screening tests, and we compared the cost required to perform these tests.
9. Lecturer at the Faculty of Agricultural Technology
Profile
Ms. Endang is one of the lecturers in the Faculty of Agricultural Technology, Universitas Gadjah Mada. Her research interests are in Gut Microbiota, Probiotic, Lactic Acid Bacteria, Mycotoxin, Food Safety, and Food Microbiology. She had experience in developing probiotic products from lab scale until they reach the industrial scale.
Purpose
Although our product didn’t classify as probiotic according to the Indonesian Food and Drug Monitoring Agency, we notice that it will be manufactured in the similar way as probiotic. We approach Ms. Endang to consult our formulation and manufacturing process to ensure it can be produced locally with reasonable price and long expiration date. This is crucial for our goal in rural area inclusivity. We also like to know more about her experience in scaling up her probiotic product.
Contribution
Ms. Endang provides us with her experience in scaling up her probiotic product. She shares how their initial research is focused in finding the suitable nutrient for the fermentation process. Then she needs to optimize the formulation of the capsule, she uses skim milk and sucrose as general cryoprotectants in her probiotics. She acknowledges that it’s hard to adhere to industry standards so that her product could be bought for scaling up. But due to extensive research and trials, her product finally got accepted by the industry. In addition to the sharing session, she invited us to take a look at her team's small factory in Universitas Gadjah Mada.
How Did We Integrate the Inputs?
Ms. Endang valuable insights have driven us to make proper planning for our scaling up strategy. We plan to use the similar method and formulation as her product with skim milk and sucrose as the cryoprotectant. This freeze drying technique is the most feasible method of preparing the bacteria according to her experience. The enteric coating used in the capsule of our product will also be similar to what she used as the purpose is the same. The only difference might be in the primary packaging of the product. While she used a plastic bottle with 10 capsules per bottle, we plan to use a single dose blister for our product since for now we propose our product to be consumed only one pill for the result to be observed.
Ms. Endang’s experience also provided us the strategy to approach the potential industry for our scaling up plan. We need to consider a lot of matters, mainly the primary production price of our product. We present our result of the discussion in our proposed implementation page.
1. Kementerian Kesehatan Republik Indonesia. 2018. Hasil Utama Riset Kesehatan Daerah 2018. 57-60. Kementerian Kesehatan Republik Indonesia, Jakarta.
2. Solikhah, S., Perwitasari, D.A. and Rejeki, D.S.S., 2022. Geographic characteristics of various cancers in Yogyakarta Province, Indonesia: a spatial analysis at the community level. Asian Pacific Journal of Cancer Prevention: APJCP, 23(4), p.1231.
3. Ferlay J, Ervik M, Lam F, Colombet M, Mery L., Piñeros M, Znaor A, Soerjomataram I, Bray F, 2020. Global Cancer Observatory: Colorectal Cancer Fact Sheet. Lyon, France: International Agency for Research on Cancer. Available from:
https://gco.iarc.fr/today/data/factsheets/cancers/10_8_9-Colorectum-fact-sheet.pdf4. Jogja Cancer Registry. 2022. Report of Dr Sardjito Hospital-based Cancer Registry in March 2022. Report of Dr Sardjito Hospital- Based Cancer Registry in March 2022. Available from: https://canregfkugmacid/laporan-data/registrasi-kanker-berbasis-rumah-sakit-dr-sardjito-fkkmk-ugm/rkbr-maret-2022
5. Yusuf, I., Pardamean, B., Baurley, J.W., Budiarto, A., Miskad, U.A., Lusikooy, R.E., Arsyad, A., Irwan, A., Mathew, G., Suriapranata, I. and Kusuma, R., 2021. Genetic risk factors for colorectal cancer in multiethnic Indonesians. Scientific reports, 11(1), p.9988.
6. Shaukat, A. and Levin, T.R., 2022. Current and future colorectal cancer screening strategies. Nature Reviews Gastroenterology & Hepatology, 19(8), pp.521-531.
