A Research Proposal For PhD Application

Exploring Novel Research in Health Policy for Thyroid Disease Management

Peiqi Guo g.peiqi@wustl.edu January 2024 A Research Proposal for PhD Application Submitted to the Department of Management, Policy and Community Health UTHealth Houston

1. Introduction

1.1 Background Information

As a vital organ, the thyroid plays a crucial role in the functioning of the human body. Thyroid hormones start participating in our body’s functioning since fetal development.1 However, thyroid disease is one of the most commonly known endocrine diseases. Not only is it well-known, but also prevalent in many countries. In the United States, about 1 out of 20 people may be troubled by thyroid disease throughout their lives.2 NHANES results from 2015-2018 also reveal a result of 5.05% standardized prevalence of thyroid disease.3 Compared to men, women have a 7 times higher chance of being affected by thyroid disease. 1 out of 8 women in the United States will be troubled by thyroid disease or thyroid disorder throughout their lifetime.2

1.2 Problem Statement

There are multiple, commonly well-known thyroid diseases: hypothyroidism, hyperthyroidism, thyrotoxicosis, thyroid crisis, thyroid cancer, and so on.4 Thyroid cancer is one of the most severe diseases among these subcategories. In 2015, an estimate of 62,000 new cases occurred in the United States. However, thyroid cancer remains relatively low in mortality rate (0.5 per 100,000) compared to other types of carcinomas.5, 6 The trend of thyroid cancer incidences keeps climbing with a 5.58 APC (Annual Percent Change) in 2010.7 This indicates a large population of patients suffering from thyroid cancer and its related symptoms. Part of the patients, especially those who have had thyroidectomy, are required to have hormone treatment for life after initial treatments such as surgery and iodine-131 radiation treatments. These patients also suffer higher risks of cardiovascular disease, especially coronary heart disease (CHD), based on a nationwide observational study reported in Nature.8 Studies have shown that although thyroid cancer survivors may gradually achieve a health-related quality of life (HRQoL) close to a healthy population in the long term, a significant number of survivors receive negative impacts on their HRQoL from thyroid cancer. More importantly, this study clearly pointed out that thyroid cancer survivors are understudied and require more study and help.9 Long-term lifetime treatments not only cause health issues but also impose enduring psychological and economic stress on patients and their families.

2. Literature Review

Health policies and economic research specifically in the thyroid cancer area are still under development, but numerous pioneer studies have been conducted. A systematic review by Kim et al. reviewed research articles related to the economic impacts of thyroid cancer. This systematic review included 49 studies. These studies featured four types of cost analysis: Cost Analysis, Cost-minimization Analysis, Cost-effectiveness Analysis, and Cost-utility Analysis. Reviewers further summarized four major research topics among these 49 articles.

First: comparing costs of hemithyroidectomy versus total thyroidectomy for low to intermediate-risk papillary thyroid carcinoma.

Second: cost evaluation of immediate surgery versus close monitoring, two treatment strategies for micro papillary thyroid carcinoma.

Third: cost evaluation of total thyroidectomy for Prophylactic Central Neck Dissection (pCND) versus low-risk papillary thyroid carcinoma.

Fourth: cost evaluation of molecular tests as a method for monitoring indeterminate thyroid nodules.10

It is noticeable that most current studies tend to focus on Differentiated Thyroid Cancer (DTC). There are fewer health economic studies on undifferentiated or dedifferentiated thyroid cancers, such as anaplastic thyroid cancer (ATC). This may be due to its extremely progressive and fatal nature, with an average 6-8 months median survival and a 35% 6-month survival rate13, 14. The extremely high fatality rate often does not leave time for ATC patients to undergo further treatments. However, more new treatments for ATC are under pre-clinical investigations and may potentially become available, such as gene therapy, novel targeted inhibitors, apoptosis enhancers, Aurora kinase inhibitors, combination treatments, and so on.15 Current studies also do not include health policy research about policies on iodine intake to prevent thyroid disease and thereby reduce the risks of thyroid cancer. Studies have pointed out that although iodine deficiency is no longer a dominant public health issue, certain subgroups, such as pregnant women, still suffer from iodine deficiency risks.16 It is necessary and valuable to study how health policies could help improve and prevent iodine deficiency in cost-efficient and effective strategies.

3. Research Thesis Topics

The primary research question should focus on how health policy can help reduce or prevent thyroid disease, specifically thyroid cancer. This research topic can be dissected into more detailed and approachable research questions. There are several ways to decompose this topic. Two possible methods include decomposing the research topic based on types of thyroid disease and health policy research fields.

3.1 Thyroid Diseases

Narrowing down to specific thyroid diseases, including hypothyroidism, hyperthyroidism, Hashimoto’s disease, thyroid cancer, and so on, is essential. The first three diseases listed are usually considered chronic and may require lifetime monitoring and treatments. Hashimoto’s disease, or Hashimoto’s thyroiditis, is a special case as it is a chronic autoimmune disease and also a primary factor in hypothyroidism.17 In addition, studies have shown a statistically significant association between Hashimoto’s disease and papillary thyroid cancer (PTC).18 Therefore, studying the health policies on Hashimoto’s disease becomes even more valuable.

Thyroid cancer as a major research topic could also be further decomposed into two subgroups: differentiated thyroid cancer (DTC) and dedifferentiated thyroid cancer (DeDTC). DTC includes papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), and Medullary thyroid cancer (MTC). DeDTC is dominated by anaplastic thyroid cancer (ATC). As mentioned above, one major difference between DTC and DeDTC is their median survival and mortality rates.15 There are numerous health economics studies on DTC, but few to none on DeDTC. Considering its extremely low median survival, it may seem not valuable to study the health policy and economics of DeDTC patients. However, it is still crucial to study how healthcare can better assist these terminal patients. For instance, researchers may study the health policies on hospice or palliative treatments for DeDTC patients aimed at improving their quality of life in their final stages. Humanistic care is as important as curing. Studies also point out the importance of health education and awareness for specific health resource disparity groups. Health policies on how to educate these groups may also help reduce DeDTC incidences.19

3.2 Health Policy Research Fields

The broad research topic may also be broken down by different research fields such as health policy analysis, health economics, long-term quality of care, decision sciences, outcome research, epidemiology modeling, etc. Taking long-term quality of care as an example, researchers may study the long-term quality of life of thyroid disease patients and their economic stress due to frequent revisits. A systematic review of current health policies related to thyroid disease is also necessary. Researchers may also combine different fields together to design comprehensive studies. For instance, it is valuable to conduct research on determining the balance between thyroid recurrence risks and cardiovascular risks induced by hormone treatment. In combination with decision science, health economics, and long-term quality of care, researchers may provide suggestions on recommended hormone treatment doses and revisiting schedules.

3.3 Thesis Topics

To be more specific, here are three thesis topics under the larger scope of health policy for thyroid disease:

(i) Effectiveness Evaluation of Iodine Warning Labels on Food Packaging for Thyroid Disease Patients

(ii) Effectiveness Evaluation of Iodine Supplement Policy on Iodine Deficiency Elimination

(iii) Health Economics Analysis for Anaplastic Thyroid Cancer Patients

We have reviewed some current journal articles in the previous sections, and most of them have not covered the above three topics yet. More importantly, research studies on these three topics are valuable and practical.20 They may provide detailed evidence, suggestions, and recommendations for the health policy-making process. Due to the length limitation of the article, the following paragraphs will focus on topic (i) and discuss a possible research plan.

4. Research Methodology

4.1 Research Design & Data Collection

This study will adopt both quantitative and qualitative research methods to evaluate the effectiveness of iodine warning labels on food packages for thyroid disease patients. The quantitative research may help analyze numerical data and provide statistical evidence for the topic. A structured survey experiment is necessary to collect numerical and categorical data from participants. Qualitative research, such as in-person or online interviews, may help construct a deeper understanding of participants’ personal experiences and perceptions of iodine warning labels. By combining these two types of research methods, this study shall provide a comprehensive understanding of the effectiveness of iodine labels and offer practical suggestions to policymakers.

As mentioned above, data collection is divided into two parts: quantitative and qualitative. The survey experiment is one of the most important data collection procedures in this study. The experiment will be divided into two parts, pre-intervention and post-intervention. After collecting demographic and basic information, participants will be asked to imagine they are shopping at a grocery store and provide four choices of products in each question. In each question, two choices are foods containing high iodine, and two choices are foods with low or no iodine. After the pre-intervention questions, they will enter the post-intervention questions. They will be informed about the two types of iodine warning labels: high iodine warning label and low iodine warning label. In these questions, they will be provided with four choices in each question as well:

1. High iodine food with a high iodine warning label.

2. High iodine food with no label.

3. Low iodine food with a low iodine warning label.

4. Low iodine food with no label.

Participants will be asked 10 questions per group in 3 groups of questions in the pre-intervention phase. Following the pre-intervention phase, participants will also be asked 10 questions per group in 3 groups of questions in the post-intervention phase. An interview will be the last procedure to collect personal experiences and subjective reflections on the shopping experiences of participants.

5. Sample Selection

Sample selection is crucial for this study to achieve objective and statistically significant results. Geographically, participants should be recruited across regions to avoid socioeconomic differences and healthcare disparities. Regarding demographics, participants are required to have been diagnosed with at least one thyroid disease, such as hypothyroidism, hyperthyroidism, thyroid cancer, Hashimoto’s disease, and related conditions. Age, gender, race, ethnicity, and other demographic requirements are not limited. This selection criteria ensures the study focuses on participants for whom iodine intake is a significant dietary consideration and ensures a diverse range of thyroid disease patients in terms of thyroid disease severity and demographic diversity.21

Participant recruitment may seek help or cooperation from university medical schools, endocrinology clinics of local hospitals, online patient groups, social media platforms, and so on.

6. Data Analysis

6.1 Data Analysis Method

Collected data will be analyzed using multiple data analysis methods. For quantitative data, the statistical hypothesis testing method will be adopted to test the hypothesis. Quantitative data will be processed through a designed data pipeline to ensure it follows ethical protocols and does not leak any participants’ personal privacy information. Descriptive statistics (such as mean, median, and standard deviation) will be initially conducted to help researchers better understand these data. In the next step, inferential statistics will assist researchers in testing the hypothesis. Depending on the data format, the student t-test could be an appropriate statistical hypothesis testing method. Qualitative analysis may require assistance from artificial intelligence technologies such as sentiment analysis and token frequency analysis through natural language processing.

6.2 Tools and Software

There are several potential tools and software to assist with data analysis procedures. Top choices include: R, Python, and their related packages. Python is at the top of the list due to its applicability, universality, and economic efficiency. Python is open source and free of charge. Additionally, it provides abundant packages to reduce workload. These Python packages include: ‘Pandas’, ‘NumPy’, ‘SciPy’, ‘Matplotlib’, ‘Seaborn’, and so on. Python is also a popularly used language for artificial intelligence and natural language processing. Its package ‘nltk’ could help with the qualitative analysis procedure.

Some other technologies may assist with data collection procedures. For instance, the front-end programming language JavaScript may help build the web-based experiment application. MySQL could be adopted as the back-end database to store data. There are also other available technology stacks that could be adopted after evaluation based on a further detailed experiment design.

7. Implications for Health Policy and Services

Findings from this research may have meaningful influence on health policy, especially for thyroid disease management and iodine deficiency populations. If the study results demonstrate the effectiveness of iodine warning labels on food packaging and improve thyroid patients’ awareness of food and dietary choices, it may illustrate the benefits of mandatory food package label policy to policymakers. For thyroid disease patients who need to restrict iodine intake, it could make it much easier for them to identify low iodine food on the shelf while grocery shopping.

In addition, the results may also provide suggestions to health education departments such as the Centers for Disease Control and Prevention (CDC). These results may provide suggestions and reference for the CDC when they make health education policies on thyroid disease prevention. Not only for thyroid disease patients, but health education policies may also have significant effects on reducing the iodine deficiency population, especially in pregnant women.22 Studies have shown that the level of iodine status of United States pregnant women is just above the recommendation cutoff of sufficiency. Considering the importance of iodine in embryogenesis, especially fetal neurological development, it is critical to increase iodine status in pregnant women.23 Health policy such as mandatory high iodine labeling may guide and help pregnant women increase their iodine dietary intake.

8. Ethical Considerations

8.1 Ethical Approval

This study involves human participants and thus is required to pass an ethical evaluation. Prior to the study’s initiation, approval from college Institutional Review Boards (IRBs) is mandatory. Supporting materials related to the research will be submitted and evaluated by the IRB. During the research and experiment, participants will be provided with detailed information on research objectives, procedures, potential risks, and other necessary related information. The participants will be required to sign consent forms and clarify their rights during the experiment. The ethical approval procedure aims to ensure the research complies with ethical requirements and provides utmost ethical and confidentiality protection to participants.

8.2 Patient Confidentiality

Patient confidentiality is one of the top critical considerations during this study. Since this study requires the recruitment of patients, a patient confidentiality procedure stricter than usual is required. The study will ensure data collection, data storage, and data usage are in accordance with the Health Insurance Portability and Accountability Act (HIPAA). Access to data and related forms will be strictly restricted to study team members only. All electronic data will be encrypted and stored in accordance with HIPAA regulations with confidentiality and integrity. These procedures will ensure participants’ privacy is respected and in accordance with legal requirements.

9. Timeline and Work Plan

Experiment Year 1

August – September: Research Proposal, Literature Review, Hospital Connections

October: IRB Approval

Experiment Year 2

November - May: Participant Recruitment, Data Collection

June: Data Cleaning and Data Analysis

July - August: Research Report Drafting & Revision

September: Report Final Review and Publication Submission

10. Budget and Resources

The majority of the software and technology used in this study are open-source and free of charge. Participant recruitment and data collection might incur the most costs in this experiment. At least two desktop computers are required. To provide an incentive, we may offer shopping gift cards on an hourly basis. If we require a sample size of 200 and provide 20 dollars per hour for participants, a total of at least 4000 USD is required for participant recruitment incentives. Including desktop computers, potential software fees, and other miscellaneous expenses, an estimated total of 8000 USD would be sufficient.

11. Limitations and Challenges

All studies have limitations and challenges, including this one. One of the top possible limitations is the number of participants. To achieve statistically significant results, a sufficient number of participants is required. However, due to various reasons, it may not be easy to find a sufficient number of thyroid disease patients who are willing to participate in this study. This is why 6 months were allocated for the participant recruitment phase.

The second largest challenge is adhering to data privacy protocols. Due to the involvement of human patients in this study, data privacy protocols such as HIPAA should be strictly enforced throughout the experimental process. These legal and regulatory requirements may pose additional challenges throughout the study procedures.

Third, but not least, this study may face selection bias, response bias, and demographic bias. These challenges should be carefully reviewed and avoided during the study design and participant recruitment procedures.

12. Conclusion

This article began by reviewing current literature on thyroid diseases and related health policies and health services research. It highlighted the prevalence of thyroid disease, especially thyroid cancer. Further, this article identified gaps between health policy and health economics research in thyroid cancer, specifically dedifferentiated thyroid cancer (DeDTC): anaplastic thyroid cancer (ATC). The study further proposes several possible research topics and focuses on the study of the effectiveness evaluation of iodine warning labels on food packages. A relatively detailed research plan was articulated, including thesis topic, research methodologies, experiment design, sample selection, proposed analysis, ethical considerations, timeline, budget estimation, and limitations and challenges. In summary, this article aims to explore some possible novel research topics in the health policy of thyroid disease management which may help improve the long-term life quality of thyroid disease patients.

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