By Sahithi Chekuri
The primary goal of this clinical study is to assess the effectiveness of the device in preventing inflammation of the duct system of the breast. Effectiveness will be determined by the absence of swelling, redness, lumps in breast tissue, and clogs, as well as reduced tenderness and no nipple inversion [1]. Special consideration will be given to nursing women, as they will be excluded from the study to decrease sources of error. Beyond physical signs of inflammation, antibody testing will be conducted to better determine the exact cause of inflammation. The device should prevent external particles or substances from coming into contact with the duct system, with no signs of the seal breaking or losing effectiveness during the wear period. Durability will be assessed by ensuring that, upon removal, no foreign substances are present. Safety evaluations will include skin checks and ultrasound imaging to assess changes in the anatomy before and after device use.
In addition to the primary endpoint, secondary endpoints will provide further insights into the device’s impact. These include assessing quality of life by evaluating user comfort and daily usability, determining cost-effectiveness to ensure affordability and accessibility, and examining sustainability by considering environmental impact and material longevity. Patient feedback will also be gathered to understand user experiences, comfort, and adherence to usage guidelines.
The clinical research for this project will follow the standard FDA clinical trial phases to evaluate the safety, effectiveness, and long-term impact of the device.
Phase 1 will involve 50 participants with no known family history of breast cancer to assess the device’s safety and tolerability. This phase will focus on evaluating skin reactions and changes to breast tissue using non-invasive imaging. Intensive monitoring will be conducted to observe any signs of skin inflammation and to ensure patient adherence to proper device application and use [2].
Phase 2 will expand to 300 participants, randomly selected to represent a diverse population with and without a family history of breast cancer and genetic mutations. The primary goal is to assess the device’s effectiveness in preventing inflammation and its tolerability. Monitoring will include measuring inflammation markers in blood and breast fluid extracted using a breast pump, assessing whether the ducts remain open or closed, and analyzing morphological changes in the duct system through non-invasive imaging such as ultrasound or mammogram. Adherence to device application and usage will also be closely monitored [2].
Phase 3 will involve 2,000 participants, continuing with a randomized selection to include individuals with and without a family history of breast cancer and genetic mutations. This phase aims to confirm the device’s effectiveness and identify any potential side effects. Researchers will monitor inflammation markers through blood and breast fluid analysis, evaluate duct openness or closure, and assess morphological changes in the duct system via imaging. Additionally, adherence to device use will be tracked, along with an evaluation of the long-term effects on skin and breast tissue [2].
Phase 4 will take place after regulatory approval and focus on post-market monitoring. Physicians will continue collecting data on patient usage, noting any side effects or complications that may arise over time. This phase will provide crucial long-term safety and effectiveness data, ensuring optimal use of the device [2].
Metrics to Test for and Length of Phases
The clinical study will be conducted in four phases, with each phase designed to assess the safety, effectiveness, and long-term impact of the device using established medical evaluations.
Phase 1 (6 months)
Check-up schedule: Once every two weeks for the first 2 months, then once a month for 4 additional months.
This phase will focus on evaluating the safety of the device on the skin and ensuring proper patient adherence. Participants will undergo medical skin evaluations to assess any reactions or irritation [3]. Ultrasounds will be used to analyze physiological changes in duct shape and size [4]. Participants will maintain journal entries detailing their device usage and attend interviews to discuss comfort, concerns, adherence, and time in high risk environments. In the first two appointments, patients will demonstrate device application to ensure proper usage.
Phase 2 (1 year)
Check-up schedule: Once every two weeks for 2 months, once a month for 4 additional months, then once every two months for 6 additional months.
This phase will evaluate the effectiveness of the device while continuing to monitor safety. Testing will include determining whether ducts remain open or closed via breast pump extraction, with open ducts producing fluid that will be analyzed for cytokine levels and inflammatory markers [5]. C-reactive protein levels will be measured in both blood and extracted breast fluid to assess systemic and localized inflammation [6]. Blood tests will also include general chemistry and a complete blood count (CBC), along with inflammatory marker assessments [7]. Imaging techniques from Phase 1, mammograms and ultrasounds, will continue to track changes in breast tissue density, duct morphology, and areas of concern. Journal entries and interviews on adherence and time in high risk environments will be conducted, and adherence to device usage will be monitored, with application demonstrations required in the first two appointments.
Phase 3 (2 years)
Check-up schedule: Once every two weeks for 2 months, once a month for 4 additional months, then once every two months for 18 additional months.
This phase will expand upon Phase 2 with a larger participant pool and a longer monitoring period. The same testing methods will be used to confirm effectiveness and detect potential side effects. Breast pump fluid extraction, cytokine analysis, C-reactive protein testing, and blood tests will continue, along with mammograms and ultrasounds to assess tissue and duct system changes. Long-term effects of device use on skin and breast tissue will also be evaluated. Patient adherence and time in high risk environments will be closely monitored through journal entries, interviews, and device application assessments in the early stages.
Phase 4 (Post-Approval Monitoring)
This phase will involve post-market monitoring to collect long-term data on the device’s use in a broader population. Physicians will continue routine mammograms and ultrasounds to assess ongoing breast health and monitor for any long-term side effects. Additionally, regular skin evaluations will be conducted to ensure that the device does not cause irritation or adverse reactions over extended use.
Each clinical trial phase will focus on different subsets of the target population to ensure that the device is effective under all sorts of conditions and test the long term impact on breast cancer prevention [9].
Phase 1
In this phase, the focus is on patients with no history of breast cancer and are in healthy condition. The ages of the patients will range from 40 to 60 years old [10]. The control group for this subset will be the group that does not use the device. Groups excluded from this phase will be those with a history of breast cancer, had breast surgery, implants, piercings, and is currently breastfeeding. If the patient has a history of breast cancer, it would be hard to pinpoint the cause of the cancer if it recurs once again and surgeries, implants, and the like would make it difficult for the device placement and adhesion. Additionally, piercings, implants, and lactation can cause inflammation and would affect the studies on comfort and usability.
Phase 2
Phase 2 will include patients with a history of breast cancer and other health conditions and the age group will range from 40 to 60 years old. In this phase, the goal is to observe the effectiveness of the device and if a patient has breast cancer due to carcinogen exposure, it would give insight on whether the device can truly prevent breast cancer. The control group would not have the device for the duration of this phase. Groups excluded from this phase would be those with modifications to the breast area, breastfeeding patients, and patients with mastectomies.
Phase 3
Phase 3 will include patients with a history of breast cancer and other health conditions and the age group will range from 20 to 60 years old. This phase will include a much larger population to test the long term impact of the device. The control group would not have the device for the duration of this phase. Groups excluded from this phase would be those with modifications to the breast area, breastfeeding patients, and patients with mastectomies.
Phase 4
Phase 4 will include patients with a history of breast cancer and other health conditions and the age group will range from 20 to 60 years old. For this phase, a large population is needed however, this is for observing the post market impact and customer satisfaction with the device. It is also useful to keep track of breast cancer incidence rates among this population. The control group would not have the device for the duration of this phase. Groups excluded from this phase would be those with modifications to the breast area, breastfeeding patients, and patients with mastectomies.
During this clinical trial, there are many possibilities of device failure or emergencies. To help the patients get the best care and for the clinical team to have all their protocols in order, a harm response plan is needed. This plan should include details on how to provide care for the patients, what protocols are in place to deal with emergencies, and how to handle damages. In the case of a device failure such as allergies, rashes, and irritation, the clinical team should prepare the patient before the experiment starts on how to handle these situations and document it. Possible solutions include removing the device, taking allergy medication, and stopping the usage of the device and informing the team when it interferes with the lifestyle. Additionally, those conducting the trial should have the patient contact information on hand and patients should also have the contacts of the investigators. For serious situations, a list of emergency hospitals and universities should be prepared and shared with all the patients and investigators. For the clinical team, when any problem arises, documenting the damage is paramount and maintaining these records in an organized manner is important. All damaged devices should be retrieved and documented. Data collected from the trials should be secured and backed up to ensure patient privacy and security [11].
To ensure validity and reliability during the clinical trial for the device, it is essential to implement methods and processes that minimize bias in order to obtain valid results. Randomization is one method used to prevent selection bias as it involves randomly putting participants in either the device group or control group. This makes sure that we can be more confident that any differences in results are because of the device, not because the group was different to begin with [10]. This makes our group more comparable and helps to draw better results and conclusions.
Another method known as Blinding is crucial for reducing performance and detection biases. Double-blinding, where neither participants nor researchers know who is receiving the actual intervention, is considered the gold standard [11]. For device studies specifically, implementing a sham device that resembles the actual device but lacks therapeutic effect can maintain effective blinding while providing a valid comparison [12]. Standardized protocols represent another essential component of bias prevention. Developing and adhering to detailed procedures for device application, data collection, and outcome assessment ensures consistency across all trial sites and participants [13]. This standardization reduces variability that could confound results.
Comprehensive training and monitoring of all personnel involved in the trial is necessary to maintain protocol adherence. Regular monitoring activities help identify and address protocol deviations promptly, preserving data integrity[14]. Well-defined inclusion and exclusion criteria help select a representative sample of the target population. Considering factors such as age, medical history, and relevant anatomical modifications enhances the generalizability of findings to real-world clinical settings [15].
Finally, addressing confounding variables is essential for isolating the device's true effect. Collecting data on potential confounders (e.g., hormonal status, genetic predispositions) and adjusting for these factors during analysis strengthens the validity of conclusions regarding treatment efficacy [16].
The primary endpoint of this clinical trial is to assess the effectiveness of the device in preventing inflammation within the duct system. This will be determined by the absence of key symptoms, including swelling, redness, lumps, clogs, tenderness, or nipple inversion. Secondary endpoints will focus on evaluating the impact on quality of life, cost-effectiveness, sustainability, and patient feedback, ensuring a comprehensive assessment of the device’s overall benefits.
A Statistical Analysis Plan (SAP) will be developed prior to data collection, outlining statistical methodologies, approaches to handling missing data, and planned subgroup analyses. This structured approach will enhance the trial’s validity and reproducibility. Intention-to-treat (ITT) analysis will be employed to include all randomized participants in their originally assigned groups, regardless of adherence. This preserves the benefits of randomization and provides a realistic estimate of the device’s effectiveness in a real-world setting. In contrast, Per-Protocol Analysis will focus on participants who strictly followed the study protocol, allowing for an assessment of the device’s efficacy under ideal conditions.
To address missing data, the study will implement multiple imputations and other statistical techniques to minimize bias and maintain statistical power. Additionally, interim analyses will be conducted at predefined points to monitor both safety and efficacy. These analyses will follow predefined stopping rules, ensuring that the trial can be terminated early if safety concerns arise or if overwhelming efficacy is observed.
A key aspect of the study design includes subgroup analyses, where predefined groups (e.g., based on age, genetic factors, race, and socioeconomic status) will be analyzed separately to explore differential effects. This ensures the device's efficacy across diverse populations, promoting equitable healthcare outcomes. To maintain the integrity and credibility of the trial, an independent Data Monitoring Committee (DMC) will oversee progress, prioritize participant safety, and ensure data reliability.
Finally, the study will adhere to established transparency and reporting guidelines, including the CONSORT (Consolidated Standards of Reporting Trials) guidelines, to ensure that the trial methodology and findings are reported with clarity and transparency. By implementing these rigorous scientific and ethical measures, the trial aims to provide robust evidence of the effectiveness and safety of the device.
Page done by: Sahithi Chekuri