Abstract

Many treatments and therapies have been developed for treating cancer; however, these treatments suffer from serious side effects. Cancer vaccines are an innovation which manipulates the patient’s own immune system to specifically target their own cancer.  The development of such therapies is critical in curing and preventing cancer. Tremendous research on cancer vaccines have been conducted over years, and several cancer specific vaccines have been approved by FDA since 1990. Even though an effective and universal cancer vaccine for all cancers does not currently exist, the recent progress on driver antigen cancer vaccines and targeted immunotherapy including CAR T-cell therapy and checkpoint inhibitor therapy show great promise. This review analyzes the feasibility of cancer vaccines and reviews some of the most recent advancements in this field.

Introduction

Cancer is a detrimental disease that has been recorded in humans as early as 1500 BCE. While there are plenty of treatment options for cancer patients, to this day no universal cure has been discovered. In 2021, more than 10 million people succumbed to cancer, with estimates of even more deaths in 2022. [28] Without any significant cure for this disease, millions of more lives will be taken each year. Cancer research is important as it helps doctors identify, cure, and prevent cancer, allowing people around the globe to have safer, longer, and higher quality lives. By understanding the biological processes of cancer, researchers can identify patterns which assist in developing ways to protect people from developing cancer and treating cancer patients. This will ultimately result in decreased occurrences of cancer and mortality. With the help of the research funding (USD 6.4 billion in 2020 alone), there have been many breakthroughs in cancer treatment. [2] One of these breakthroughs is called targeted immunotherapy, which is also known as the cancer vaccine. [3] This therapy uses the patient’s own immune system to destroy cancer. Although no complete cure has been fully developed, these cancer vaccines have been heavily researched and are used in patients. With cancer vaccines being one of the most prominent and potential cures to cancer in the future, this review briefly discusses the effects, processes, and results of cancer vaccines.

What is Cancer?

Cancer is a disease caused by an uncontrolled division of abnormal cells in parts of the body. There are many types of cancers such as breast, lung, colon, skin cancer, etc. As of 2022, breast cancer is the most common cancer in the US [12] whereas lung cancer is the most common cancer in China. [13] Statistics show that about 60% of people who are diagnosed with metastatic breast cancer also develop lesions in the lungs. [26] Metastatic cancers are when cancerous cells spread to another part of the body, which is commonly found in breast, colon, kidney, lung, among other cancers. An example of the metastasis can be seen in kidney cancer, where the cancer spreads to adrenal gland, bone, brain, liver, and lung. 

Although cancer can develop and spread to different organs within the body, they share some similar symptoms such as fatigue, weight loss or gain, swelling, unusual bleeding or bruising, headaches, among many other symptoms. [34] The most severe symptoms usually are experienced by bone and pancreatic cancer patients. [33]

In figure one, it shows that patients that are diagnosed with brain cancer usually have the lowest 5-year survival rates (12.8%) whereas testis cancer has the higher survival rate (97%) in England. [9] Interestingly, some cancer patients can live with their cancer as long as they continue treatment such as melanoma, breast, prostate, testicular, cervical, and thyroid cancer patients as the 5-year survival rates are highest.

It is scientifically accepted that the universal cause of cancer is damage to genetic material i.e. DNA. Chemical disruption of the nucleotides that hold the DNA chains together results in genetic mutations once the DNA replicates itself. Loss or rearrangement of these nucleotides alters the genetic information contained in the DNA i.e. mutations. As can be seen in figure two, double strand breaks can also cause rearrangement of the chromosome structure, which could disrupt a gene and ultimately lead to mutation(s). However, these mutations can be avoided if the DNA repair system recognizes the DNA damage as abnormal structures and repairs it before the round of replication. [15] Alterations in DNA sequence result with improper cell cycle maintenance and functions. The sequence of DNA is important for expressing critical proteins in and on the cells of the body. When the sequence changes, that directly impacts the function of these proteins. Depending on where this damage occurs and which protein is affected, the function of the cell changes and can lead to developing cancerous cells. 

There are a few exogenous factors that may cause DNA damage, and eventually cancer. These include lifestyle habits, such as, but not limited to, smoking, unhealthy diet, or exposure to toxic chemicals. DNA damage resulting from continuous smoking increases the chances for developing lung cancer, which can then spread to other parts of the body. [23] An unhealthy diet could lead a patient into obesity, which is a risk factor for various cancers such as colon, breast, kidney, etc. Maintaining a healthy body weight and also reducing alcohol intake can lower the risk of developing these cancers. [7] Exposure to heavy metals such as cadmium, arsenic, and nickel [18] (from factories or industrial productions), asbestos (aging and unmaintained buildings), and ultraviolet light (from the sun) can also cause damage to DNA in cells, leading to various cancers. There are many dangerous carcinogens such as PAH, N-nitrosamines, aromatic amines, 1,3-butadiene, benzene, aldehydes, and ethylene oxide which can cause damage to DNA.  These carcinogens can be found in natural resources such as UV Light or viruses, or man-made waste like automobile fumes and cigarette smoke, and can cause mutations to the DNA, increasing the likelihood of cancer diseases. Some cancers can also be hereditary where one or both parents carry altered genes and carry that on to their offspring(s). Most common hereditary cancers are breast and colon. [37]

The main effect cancer has on the body is weakening of the immune system. For example, leukemia, lymphomas, and multiple myelomas spread into the bone marrow, outcompeting with the bone marrow cells for space and nutrients. [42] When this happens, the bone marrow won’t be able to generate white blood cells to fight infections in the body. Without a strong immune system, there is no protection against illnesses, leaving patients very vulnerable to other diseases. Not only do blood cancers affect the immune system, but also solid tumors. A tumor is a solid mass of tissue consisting of abnormal cell groups. Solid tumors grow on bones (sarcoma), skin (melanoma), lung (carcinoma), and other organs and glands. Malignant cells from the tumors avoid immune elimination through loss of antigenicity (ability to interact with immune cells and antibodies) and/or loss of immunogenicity (ability to provoke immune response). [24] The degree to which the tumor overrides the immune system on tumor type and lesion. 

Many treatments have been developed to help cure or slow the progression of cancer. The most common treatments include surgery, chemotherapy, and radiation. [27] Surgery is the physical removal of a solid tumor/mass from the patient. Side effects of surgery include blood clots, bleeding, infections, damage of other organs, and reaction to drugs. [32] Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy has negative side effects in which the immune system becomes weak, and infections are more probable. This is because chemotherapy is meant to kill fast growing cells, but they could also accidently affect healthy cells that are also fast growing. Radiation therapy uses x-rays, particles, or radioactive seeds to destroy the cancer. Radiation slows down the abnormal growth rate of the cancer cells. Side effects of radiation include fatigue, hair loss, memory or concentration problems, nausea, skin changes, and blurry vision. Most recently, targeted immunotherapy has been developed and considered to be the “cancer vaccine” for patients. This therapy focuses on using a person’s own immune system to fight cancer. The most prominent immunotherapies use CAR T-cell therapy and checkpoint inhibitors to fuel the production of cancer fighting cells to attack cancer cells. [41]

What Are Vaccines?

A vaccine is a substance used to stimulate the production of antibodies to provide long term immunity against a disease. The most common types of vaccines are live-attenuated vaccines, inactivated vaccines, and toxoid vaccines. Live-attenuated vaccines are created by using a weakened form of germ that causes the disease. These vaccines are similar to the natural infection, so it provides a strong and long lasting immune response. A limitation to this type of vaccine is people with weak immune systems, chronic health problems, and organ transplant recipients may not be eligible to receive such vaccines. Live-attenuated vaccines are used for various diseases including measles, rotavirus, smallpox, chickenpox, and yellow fever. 

Inactivated vaccines use the deactivated version of the germ that causes the disease. The inactivated vaccines are not as strong or long lasting as the live-attenuated vaccines. This type of vaccine is a safer alternative for those with weak immune systems and chronic health problems since they are weaker than the live-attenuated vaccines. Booster shots are required for inactivated vaccines to ensure that the patient gets longer immunity against diseases. Inactivated vaccines are used for hepatitis A, flu, polio, and rabies. Toxoid vaccines use a toxin made by the germ that causes the disease. It creates immunity against the germs that cause the disease, but not the disease itself. Similar to the inactivated vaccine, it also requires booster shots for an ongoing immunity against diseases. Toxoid vaccines are used to protect against diphtheria and tetanus. [40]

With the outbreak of the COVID-19 pandemic, a new type of vaccine has been developed and globally used to prevent the spread of this deadly virus and maintain the lives of billions. These vaccines are mRNA based, which means inactivated regions of proteins from the virus are genetically encoded to be expressed on the surface of healthy cells. Once these proteins are detected by the immune cells, an immune response is generated. The main difference compared to the vaccine types above is that these proteins remain on the surface of the cells as long as the cells are in the body. [29] This method has been researched for more than a decade but has only been used in humans since the pandemic outbreak. Given that this technology is still in its infancy, there are many areas of development to increase the efficiency and longevity of mRNA vaccines.

Innovating Vaccines against Cancer

Cancer has always seemed to be the greatest enigmas of the modern day as no universal cure has been developed. The idea of a cancer vaccine – not a direct cure, but a prevention against cancer – is an absolute breakthrough as it has the potential to drastically decrease the mortality and infection of cancer throughout the globe. Unlike the types of vaccine mentioned in the last section, cancer vaccines take advantage of proteins found in or on cancer cells. [41]

The progress to the current cancer vaccines in early trials has come a long way. Immunotherapy was first developed in 1891 by William Coley, also known as the “father of immunotherapy.” Coley attempted to leverage the immune system through injecting patients with bacteria or bacterial products. His belief was that forcefully activating the immune system will generate a response against inoperable cancers. While his approach was not entirely understood or accepted by professionals and healthcare providers at the time, he was able to treat about 1000 cases of bone and soft-tissue sarcoma where patients’ tumors decreased in size after being injected with these inactivated bacteria. These short lived, “immunotherapy” injections were referred to as Coley Toxins. [39]

About a century later, the first FDA approved cancer vaccine (1990) was BCG (Bacillus Calmette-Guérin) which uses a weakened strain of TB (tuberculosis) bacteria, and it triggers the immune system to protect against the infection that results in early-stage bladder cancer.  [6, 10] A second FDA approved cancer vaccine (2010) is the Sipuleucel-T, which is an autologous cellular immunotherapy used for patients with metastatic castration-resistant prostate cancer (mCRPC). The vaccine activates the multiplication of immune cells and attacks prostate cancer cells using an antigen (one or more proteins on the surface of cancer cells that induce an immune response), that is highly specific to prostate cancer. [16, 8] A third FDA (2015) approved cancer vaccine is called T-VEC (Talimogene laherparepvec). T-VEC is an immunotherapy for treatment of melanoma skin cancer. T-VEC is made with a weakened version of herpesvirus in which it can break down cancer cells without affecting normal cells. Unlike other cancer vaccines, T-VEC is injected directly into the tumor. [38]

While two of the three cancer vaccines mentioned primarily function on established tumors/cancers, the more traditional way of thinking about vaccines is to prevent the disease from occuring. Since cancer is a genetic-based disease for the most part, this has been the greatest challenge in developing immune-shields against cancer. However, there are some “traditional” vaccines that immunize against viruses known to be linked to development of cancer. Epstein-Barr virus (EBV) is linked to nasopharyngeal cancer, stomach cancer, and Bukitt/Hodgkin lymphoma. The EBV vaccine targets EBV glycoprotein gp350, which is found in the virus and on virus infected cells. Gp350 is the main target for neutralizing antibodies in the body and causes cells to target a specific antigen. [31] Human papillomavirus (HPV) causes most cervical cancers including vulva, vagina, penis, anus, and oropharynx cancer. [5] The HPV vaccine is a non-infectious recombinant vaccine that stimulates the body to produce antibodies. These antibodies bind to specific parts of the HPV and signal to the immune cells to destroy these virus particles, preventing viral infection. Hepatitis B virus (HBV) causes chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. [21] The HBV vaccine is also a recombinant vaccine and it work by causing the body to produce its own antibodies against the disease. [20,19] Human herpes virus (HSV) has been linked to cause cervical cancer. [22] While there aren’t any approved vaccines against HSV, there is a potential mRNA-based vaccine that is being studied to prevent HSV. The concept of this vaccine is to provide a strong antibody response and drive immune cells to kill HSV particles. [30, 14]

Many years of commitment have been put into developing immune cell-based therapies. Although there were many obstacles in developing and implementing this therapy, immune cells that were engineered to treat cancer called CAR T cells (approved by the FDA in 2017 and created by Novartis) were discovered. CAR T cells, also known as chimeric antigen receptor T cells, have been implemented in cancer treatment including lymphomas, leukemia, and myelomas. CAR T-cells are referred to as a living drug as they orchestrate the immune system and directly kill pathogenic cells. Immune T cells are harvested from patients and are customized for each patient. This results with highly engineered CAR T cells that can recognize and bind to specific proteins or antigens on the patient’s own cancer cells prompting their elimination. These T cells are customized because normal T cells are incapable of binding to these antigens. Once these cells are injected, they are directed towards cancer cells that express the antigen the CAR is designed to target. One major drawback is that since cancer cells are abnormal human cells, these antigens are sometimes expressed on healthy cells leading to off-target toxic effects. Not only are CAR T cells referred to as a cancer therapy, but they can also be considered a vaccine because the cells remain in circulation and proliferate inside the patient, potentially protecting against any recurrence of the cancer. [11]

In 2022, researchers believe they have found another viable cancer vaccine based on positive clinical trial results. Olivera Finn, a professor of immunology at the University of Pittsburgh was able to identify a colon tumor-specific antigen known as MUC1. Finn’s team was able to create a MUC1-based vaccine to help patients with premalignant colon polyps. This vaccine works by triggering an immune system response to attack the colon polyps. The vaccine reduced recurrence rates by 38% in the clinical trial, proving its effectiveness. Another example of the use of an antigen is the HER2, which is a protein found in about 25% of breast cancers. Knutson and Amy Degnim, who are breast surgeons at Mayo Clinic in Minnesota designed a HER2 vaccine used in a trial of 22 patients with invasive breast cancer. This vaccine is like the MUC1 vaccine where it targets the antigen, provokes the immune system, and kills cancer cells. The results were very promising, with only two recurrences after two years. [11] Although the timetable for a truly universal cancer vaccine is unclear, these examples of clinical trials show the potential of these vaccines to cure cancer, and how researchers are setting the stage to make cancer history. [1]

Conclusion

The most prominent method that researchers have been developing these cancer vaccines is using “driver” antigens, which acts as a target for the immune system. Although these cancer vaccines seem promising, a limitation is that tumors express an array of antigens that are also common in healthy cells, making it difficult for researchers to identify tumor-specific antigens. Cancer vaccines are not like live-attenuated or inactive vaccines where the germ is already placed in the body. Rather, they use these antigens to make the immune system purposely attack the tumors to prevent recurrence. Cellular immunotherapies introduce the least risk of toxic side effects since the cells are from the patient and they are engineered to target the cancer specifically. Similar to CAR-T therapy, researchers have developed CAR-macrophages (CAR-M) where these immune cells are also engineered in a similar manner to CAR-T cells. [17] However, a unique method to activate macrophage immune cells is to use antibodies, proteins and peptides to block interactions responsible for survival of the cancer cells and then only have activating signals against the cancer. [4] This is also known as checkpoint inhibitor therapy. Many breakthroughs along the studies of a cure for cancer have arisen recently, and it may just be a matter of a few years before the deadliest disease is eradicated. 

References

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About the author

Jonathan Lu

Jonathan Lu is a senior at the Concordia International School in Shanghai, China. Jonathan has a passion for Physics, Materials Science, Chemistry, Engineering, Biology, and all things basketball. In the paper, Jonathan analyzes the development of cancer vaccines and immunotherapy.

The post Cancer Vaccines: The Advancement of Immunotherapy appeared first on Exploratio Journal.

Abstract

This paper describes the concept of Human Centred Design (HCD) and its applications in the health sector. Inculcating the five core principles of HCD can provide a more effective and efficient approach in the processing and production of medical devices, vaccines, diagnostics, and drug development. The application of HCD principles is of importance in developing a patient centric focus in developed health care systems but arguably is far more important in areas of the world where factors mitigate against the development of sophisticated health care options.  HCD approaches will be discussed in this context, using working examples from the area of diagnostics, vaccines, medical devices and drug development and their application in underdeveloped countries.  Comparisons will be made between the HCD approach and traditional approaches to medical innovation.

Introduction

What is Human-Centred Design (HCD)?

HCD is an approach to interactive systems development that is used to make systems usable and useful by focusing on the users, their needs, and requirements. [3] By applying human factors/ergonomics concepts and usability knowledge and techniques, HCD enhances effectiveness and efficiency and in turn improves human well-being, user satisfaction, accessibility, and sustainability. Using this method during production could also possibly counteract adverse effects of use of some systems on human health, safety, and performance.

The concept was first introduced by Mike Cooley during a professional transition to computer-aided design with an aim to improve user experience. [3] HCD was previously known as participatory design and was birthed in ancient Athens. As time passed This concept soon began to slither its way the world and flourished there under names such as Design Science, Universal(inclusive) design, transformation design, service design and user- centred design.

Principles of Human-Centered Design:

1. Empathize: Learn about the target audience for the product. This is done through surveys, questionnaires, immersion into the audience, meetings, self-documentation, user experience interviews, etc.
2. Define: Establish key questions based on the audience requirements and the product. Identifying the theme, interpreting findings, sorting through the findings, framing opportunities, and setting a ‘Design Challenge’ are involved in this process.
3. Ideate: Brainstorm and create solutions. The problems may involve including factors such as visual, tactile, experiential aspects of the product. 
4. Prototyping: Build the representations of one or more ideas to introduce to users record their response. 
5. Test: The user feedback from the created prototypes is used to improve the product to ensure complete user satisfaction. 

HCD principles have proven to be useful in a number of settings, especially in the health industry.

One of the most prominent examples that demonstrates this is Project Firefly. Details of this project will be highlighted in the section below.

Why is such an approach necessary in the health sector?

Communication between the health industry and the public is not satisfactory, and since patient autonomy and communication is one of the main pillars of medical ethics this is vitally important.  which may mislead people or leave them in the dark when it comes to their own healthcare. This may be because the quality of education in various parts of the world (especially underdeveloped countries) does not always allow everyone to gain a good understanding of the scientific processes that guide our healthcare system. 

The industry being science driven is essentially top-down managed focussing resources on wealthy markets and always with a view to profit margin.  In a world where healthcare is of utmost importance in places such as third world countries, this approach does not bode well for attaining acceptable global health. [1]

Figure 2 shows a global map of countries that produce and sell drugs whereas Figure 3 displays the distribution of where these drugs are being purchased. It is clearly observed that the global health market is mostly confined to first world countries or countries where wealth is abundant. Big pharmaceutical companies are gradually starting to realise that there is a massive market in underdeveloped countries. This should seem abundantly clear especially as we are paving our way through a global pandemic. Moreover, disease outbreaks more often than not, tend to take place in underdeveloped countries.

There are some other factors that generally may not be considered during the production of healthcare equipment and drugs. Some communities may have religious beliefs that may go against some treatments or drugs. Poverty is one of the main concerns that stand in the way of global health. Incorporating HCD principles during development can definitely help break through some of these barriers. Moreover, the global health market is mainly centered in first world countries or countries where wealth is abundant. Big pharmaceutical companies are starting to realise that there is a massive market in third world countries, especially since the onset of pandemics, disease outbreaks, etc., tend to happen in underdeveloped countries. The same can be said about countries where cultural and political factors play a big role in the acceptance of certain forms of healthcare. There may not be a very potent market in such areas as the healthcare provided to them in the form of drugs, vaccines or even certain medical devices may not be acceptable. This is where HCD can really dive into production and really find out the specific requirements of such communities which will in turn give rise to new markets and essentially benefit all those involved.

Applications of HCD in the Production of Medical Devices

Even with the presence of such a vast variety of lifesaving technology, only few of these benefit communities with minimal resources. To begin with the high purchasing price is an obvious issue, on the other hand the World Health Organization found that nearly three quarters of devices provided by industrialized countries are not used when they reach low resource communities. There are many possible reasons as to why this occurs:

• Power fluctuations in such areas can cause most of the medical and diagnostic devices to fail.
• High temperatures, high humidity, dust, insect infiltration, poor availability of spare parts and low staff-to-patient ratio can lead to unsatisfactory treatment for the patients.

To produce efficient and well-designed products that are functional in locations with minimal resources, medical devices need to be developed in such a way that they cover the requirements of the local patients, clinics, hospitals, and communities.

Applying this concept during the process of development of medical devices will have the following advantages:

• It will highlight the essential requirements of the stakeholders that are involved in the success of the medical technology and will in turn bring about a positive change in global health.
• The chances of producing more creative solutions will increase
• The information generated using this concept will help in the quick evaluation of similar devices completely avoiding months of monotonous testing.
• Laying out the basic targets to hit will help come up with a solution that satisfies all the essential needs of the patients and the stakeholders.

A case study that highlights all these key features is discussed below.

Case Study: FIREFLY PROJECT [2]

Jaundice affects a large population of new-born babies all around the world every year, 100,000 cases of which become fatal and leaving at least 50,000 babies disables. This problem most commonly occurred in Africa and South Asia. To treat this condition, new-borns require a treatment known as phototherapy which is a minimally invasive treatment the shines blue light on the skin of the affected new-borns. This allowed the new-borns to pass the excess bilirubin out of their bodies through urine or stool, so it does not cross the blood-brain barrier. Design that matters (Dtm), Medical Technology Transfer and Services (MTTS) and East meets West foundation combined their resources and knowledge and became instrumental in the production of better tools to treat new-born jaundice in low- resource hospitals.

The following steps took place:

1. First thing that was done was defining the team, identifying the appropriate team members, users, stakeholders and scanning through the available technologies and existing approaches
2. The identified stakeholders, users were interviewed, and every single requirement is listed and defined.
3. Consolidation of the data and beginning of the ideation process. From the information gathered, the aim was to create a device that would meet the following requirements:

• Effective- device must provide intense phototherapy and also look like it is providing intense phototherapy. The perception of efficiency is important to drive stakeholder adoption
• Comforting- aiming to make a ‘high-tech bird’s nest’; comfortable for the new-born and aiming to achieve more area of light shown on the skin
• Maintainable- should be easy to clean with high grade alcohol or disinfectants to prevent the risk of infection. It should also be durable to ensure long life and reduce cost long term. This was done by ensuring the absence of moving parts to prevent wear and tear.
• User friendly- People with low community level education and skillset should be able to use this device hassle-free.

4. Ideation and prototyping began using the abilities of the high power- long lasting- LEDs that function low consumption of electricity, to their advantage. The shape of the device was in the form basket that could fit in small places in crowded hospitals hence allowing them to accommodate more new-borns.

5. When undergoing testing, user and stakeholder feedback was taken and incorporated into the final prototype. One interesting point that was noticed is that when one of the nurses covered the shade of the basket with a cloth, the exposure to the blue light was prolonged and more intense and hence, was more effective. It soon became mandatory to cover the basket with a sheet. Such a simple change would have not been left unnoticed if it were not for this all-rounded approach

Conclusion: This approach to Project Firefly created a medical device that rid local hospitals of the requirement and maintenance of high-cost equipment, excessive overcrowding, low performance, or failure to conduct treatment due to power fluctuations or complicated operation.

Application of HCD in the Development of Vaccines

The development of any kind of vaccine involves several steps: exploration, multiple phases of clinical development, registration, and launch. Application of the principles of HCD may result in a shorter production period of vaccines. By doing so, the durations of clinical development may decrease leading to the faster administration of the vaccine. [1]

Even during a crisis as big as the current one known as covid-19; the development of the vaccine was undertaken in a span of few months whereas normal vaccines take years to get approval. This leads the population to doubt the viability and efficacy of the vaccine itself. Moreover, the quality and future consequences of the vaccine may be put in doubt due the top- down managed companies that are racing to develop a vaccine for COVID-19 and get approval without going through all the stages of its clinical development.

Given that HCD principles are to be incorporated in vaccination programme, the following steps are to be followed:

1. Study of disease epidemiology: Getting a deep understanding of the frequency, risk factors, causes and the general target population though HCD
2. Collecting and defining: Using this information to create a vaccine that meets all safety and efficacy requirements
3. Accessibility: The vaccine needs to be accessible to the target population through reliable delivery facilities. They may also need to be stored in controlled environments, and if this is the case for third world countries, a detailed plan must be laid out to ensure the safe transport and storage of the vaccine. This is where an HCD approach may benefit the system.
4. Cultural and political acceptance: Communication is an essential factor here to ensure maximum participation in the vaccination programme.
5. Cost effectiveness: This can be ensured through local human centric approaches and local delivery.

Application of HCD in Drug Development

As seen in the above figure, third world countries have a very minimal share and participation in the global pharmaceutical market. [5] This is unfortunate as it is very evident that pharmaceutical companies have a big opportunity for a market here given, they follow an HCD approach during drug development. Like vaccines, drugs also require about 10-12 years to go through all the phases of production (drug discovery, preclinical development, clinical development, approval and then to the market) making the final product extremely expensive. This leads big pharmaceutical companies to target bigger and more reliable markets making the availability and cost of these drugs in third world countries questionable. Using an HCD approach during drug development and administration will benefit both- pharmaceutical companies and the people in need of medication.

Drug Repurposing:

This is one such HCD approach used during drug and administration. Drug repurposing is the concept of re-using previously existing drugs for new therapeutic uses. [6]

For example: Chloroquine is a drug that is generally used to treat or prevent malaria. However, after studying the mechanism and working of the drug, it was found that chloroquine may also be used to treat symptoms of Covid-19. [7]As the drug is being repurposed and not developed from scratch and all the existing side-effects are known, it in turn boosts availability and affordability of the drug. Covid-19 has now spread to every continent and having affordable medication to treat its symptoms is essential.

Applications of HCD in Diagnostics

One important aspect to cover during the development of diagnostic devices is the concept of surveillance which is also one of the foundation principles of HCD.

What is surveillance? 

The systematic, on-going collection, collation, and analysis of data for public health purposes to assess and respond as necessary- it is the continuous collection of information to inform action.

Surveillance performs the following tasks:

• Understanding trends and developments quickly at the site of action.
• The large amount of data that is collected from surveillance can be used for research purposes.
• Helps to identify the pattern and prevalence of the disease.

Why do we need surveillance?

• Helps in detecting outbreaks and intervening in affected areas
• To monitor ongoing threats
• To evaluate public health care policies
• To ensure that all necessary information is acquired based on which limited resources may be used efficiently

Affordable and reliable diagnostic equipment is a rarity in third world countries. This is where an HCD approach along with surveillance can help create satisfactory diagnostic equipment.

What to expect from such diagnostic equipment?

• Needs to be affordable for low-income populations.
• Easy to use and interpret.
• Must stay viable during storage in their respective environmental conditions.
• Must be reliable and accurate.
• Must be suitable in communities with cultural and religious principles.
• Some equipment may require a certain level of privacy.

An example of a diagnostic equipment that was designed using an HCD approach has been explained in the case study below by the University of Washington. [8] This is a perfect example to illustrate the importance of surveillance and the drastic changes in diagnosis and treatment it can bring about.

Case Study: 

In this study, the entire continent of Africa was broken down into blocks of 9.6 square mile area. Each block was assigned a local group of people to monitor the prevalence of HIV which produced a detailed image of where this disease was mostly prevalent in Africa. It was found that HIV affected more areas in South Africa and the epidemic was found to be non-existent in the majority of the content. Such a fine-grained image of the distribution of this disease would not have been discovered if this surveillance had been done at a national or province level. This information that was collected had a huge impact in the diagnosis, treatment, and prevention of HIV in Africa.

The problem that the officials faced now was that due to the population’s mobility, the infection was spreading faster and administration of treatment for the infection proved to be difficult as each individual was asked to pick up their own prescriptions. This led to many patients missing several doses. Consequently, a new policy was introduced that allowed members of the local HIV-positive peer support groups to pick up and distribute each other’s medications. It is clearly visible here that an HCD approach to treating this infection provided a simple solution that had a drastic impact on the population’s health.

This study led to the discovery of self-testing HIV kits that met all the requirements of diagnostic equipment as listed above and proved to be extremely useful in preventing the spread of HIV. [9] 

It provided the following benefits:

• Diagnose HIV status.
• Diagnose whether HIV medication has been taken (irregular administration of medications leads to aids).
• Negates the need to travel to a clinic.
• Test can be taken in privacy eradicating the fear of the heavy stigma that hovers around this disease

Conclusion

HCD has proved to have a lot of promise in the health care industry. These are only a few areas where it can be applied. There is much scope for its principles in the future of healthcare and we are only beginning to tamper with its possibilities. It can be concluded that using this concept and appropriate resources, any given project can be created and function at its maximum potential. HCD principles serve as the necessary guidelines to do so.

References

1. WHO global strategy on people-centered and integrated health care services
2. Neonatal Phototherapy and Vitals Monitoring Device- Team 49| Parul Agarwal, Marty Puru and Hiba Shahid| ECE 445 Design Review Document|2/22/18
3. Alexandra Nemeth. https://blog.movingworlds.org/an-introduction-to-human-centered-design/
4. Michelle L Henninger  1 , Carmit K Mcmullen  2 , Alison J Firemark  3 , Allison L Naleway  4 ,  Nora B Henrikson  5 , Joseph A Turcotte. Perm J. 2017;21:16-191.
5. Matej Mikulic, Sep 4, 2020. /www.statista.com/statistics/309425/prescription-drugs- market-shares-by-top-companies-globally/
6. Sergey A. Shiryaev1, Pinar Mesci2, Antonella Pinto1, Isabella Fernandes2, Nicholas Sheets3,
   Sujan Shresta3, Chen Farhy1, Chun-Teng Huang1, Alex Y. Strongin1, Alysson R. Muotri2 &
   Alexey V. Terskikh1 Scientific Reports | 7: 15771 | DOI:10.1038/s41598-017-15467-6
7. Drug repurposing: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758385/
8. Laura Dwyer-Lindgren etal. (2019) Nature, 570, 189-193. Mapping HIV prevalence in Sub-Saharan Africa between 2000-2017.
9. WHO prequalification reports. Mylan test kits lateral flow for HIV. www.who.int/diagnostics_laboratory/evaluations/pq-list/190708_pqdx_0320_090_00_pqpr_mylan_hiv_self_test.pdf

About the author

Sai Vandana Srinivasan

Sai is a student at the Manipal Institution of Technology.

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