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Colorectal cancer screening by fecal occult blood testing has been an important public health test and shown to reduce colorectal cancer–related mortality. However, the low participation rate in colorectal cancer screening by the general public remains a problematic public health issue. This fact could be attributed to the complex and unpleasant operation of the screening tool.
This study aimed to validate a novel toilet paper–based point-of-care test (ie, JustWipe) as a public health instrument to detect fecal occult blood and provide detailed results from the evaluation of the analytic characteristics in the clinical validation.
The mechanism of fecal specimen collection by the toilet-paper device was verified with repeatability and reproducibility tests. We also evaluated the analytical characteristics of the test reagents. For clinical validation, we conducted comparisons between JustWipe and other fecal occult blood tests. The first comparison was between JustWipe and typical fecal occult blood testing in a central laboratory setting with 70 fecal specimens from the hospital. For the second comparison, a total of 58 volunteers were recruited, and JustWipe was compared with the commercially available Hemoccult SENSA in a point-of-care setting.
Adequate amounts of fecal specimens were collected using the toilet-paper device with small day-to-day and person-to-person variations. The limit of detection of the test reagent was evaluated to be 3.75 µg of hemoglobin per milliliter of reagent. Moreover, the test reagent also showed high repeatability (100%) on different days and high reproducibility (>96%) among different users. The overall agreement between JustWipe and a typical fecal occult blood test in a central laboratory setting was 82.9%. In the setting of point-of-care tests, the overall agreement between JustWipe and Hemoccult SENSA was 89.7%. Moreover, the usability questionnaire showed that the novel test tool had high scores in operation friendliness (87.3/100), ease of reading results (97.4/100), and information usefulness (96.1/100).
We developed and validated a toilet paper–based fecal occult blood test for use as a point-of-care test for the rapid (in 60 seconds) and easy testing of fecal occult blood. These favorable characteristics render it a promising tool for colorectal cancer screening as a public health instrument.
Colorectal cancer ranks globally as the third-leading and second-leading cancer type in terms of incidence and mortality rates, respectively. The incidence rate of colorectal cancer continues to rise because of aging populations and lifestyle changes. The continuous increase in its incidence rate has brought considerable health burdens worldwide [
Among the screening methods described earlier, flexible sigmoidoscopy and colonoscopy are the gold standard primary screening methods [
To address this issue, we herein proposed a toilet paper–based fecal occult blood test (JustWipe) encompassing a toilet paper designed for fecal specimen collection and the reagents required for fecal occult blood test. For fecal specimen collection, we evaluated the working performance of the specially designed toilet paper. Moreover, we also developed and verified the analytical reagents used in the toilet paper–based tool. Based on the toilet paper design and analytical reagents, comparisons between the toilet paper–based tool and commercially available Hemoccult SENSA, as well as routine hospital fecal occult blood tests, were conducted to validate the new tool’s clinical utility and show that by using the novel toilet paper–based fecal occult blood test, we could easily collect fecal specimens in a regular buttocks-wiping move after defecation and detect fecal occult blood rapidly and accurately.
The toilet paper–based fecal occult blood test (JustWipe; Sigknow Biomedical Co Ltd) contained the testing paper for fecal specimen collection and the necessary reagents, as illustrated in
Design of the toilet paper-based fecal occult blood point-of-care test (JustWipe). TMB: 3,3’,5,5’-tetramethylbenzidine; H2O2: hydrogen peroxide.
The appearance of the JustWipe: (A) The front side of the toilet testing paper with the hand handle side is clearly marked. (B) The backside of the toilet testing paper has a stool collection area with water repellent polyester cloth.
Comparison between JustWipe and typical fecal occult blood testing processes.
To examine the variation in specimen collection using the toilet paper–based fecal specimen collection, 18 volunteers were recruited for the evaluation. For three consecutive days, each volunteer collected a specimen after defecation using the JustWipe method directly with a testing paper device. The weight of the testing paper was measured before and after collecting the specimen. The specimen weight from the testing paper was calculated by subtracting the testing paper weight before wiping from the testing paper weight after wiping.
We conducted a qualitative performance evaluation to determine the limit of detection of the reagents used in JustWipe according to Clinical and Laboratory Standards Institutes (CLSI) EP12-A2 User Protocol for Evaluation of Qualitative Test Performance [
We evaluated both intraassay and interassay repeatability based on CLSI EP12-A2 [
The reproducibility between untrained users (n=50) and trained medical staff (n=2) using the test reagents was evaluated based on CLSI EP5-A3 Evaluation of Precision Performance of Quantitative Measurement Methods guidance [
We collected 70 convenience nonduplicate stool specimens from the central medical laboratory of Chang Gung Memorial Hospital Linkou branch between September 11, 2019 and March 24, 2020. The study was approved by the Institutional Review Board of Chang Gung Medical Foundation (No. 201901287B0). The stool specimens were collected in wards by nurses and placed into routine stool collection tubes [
Study design flowchart. FOBT: fecal occult blood test.
We recruited 58 volunteers to use JustWipe as a point-of-care test in the period between March 1, 2019 and January 31, 2020. The volunteers were recruited from the Chang Gung Memorial Hospital and Chang Gung University. The study was approved by the Institutional Review Board of Chang Gung Medical Foundation (No. 201900133B0). The volunteers were asked to follow the instructions of JustWipe after defecation: the volunteer wiped his or her buttocks to collect stool specimens with the toilet paper–based fecal specimen collection device, followed by the steps of folding the device and applying the reagents. The volunteers interpreted the results themselves after 60 seconds of reaction. Subsequently, for testing with Hemoccult SENSA, the volunteers collected the rest of the specimens (a volume greater than that of a thumb) and sent the specimens to the medical staff within 20 hours which were kept at room temperature or stored between 2 ℃ to 8 ℃ and shipped to the laboratory next day. For Hemoccult SENSA (Beckman Coulter), the stool specimens received by the laboratory were then tested by medical staff according to the instructions of Hemoccult SENSA.
The questionnaire was designed to assess the usability and user preference of the JustWipe. The questionnaire contained 12 questions about the user’s experience of the toilet paper–based fecal occult blood test (
Questionnaire used for usability evaluation. There were 12 questions on the questionnaire to assess the three aspects of the test, namely, operation friendliness, ease of reading the results, and information usefulness.
Group | Number | Items | Average agreement, % |
Information usefulness | 1 | Did you know that the detection target is fecal occult blood? | 100 |
2 | Did you know that the testing result is not an indicator of cancer? | 98.6 | |
3 | Did you know that the testing result is only for physical conditions? | 100 | |
4 | Do you know what to do after testing? | 88.3 | |
5 | If the test result is positive, would you go to the hospital for further examination? | 93.8 | |
Operational friendliness | 6 | Are the two bottle designs easy to identify? | 89.0 |
7 | Do you understand all of the items in the device using the instruction manual? | 86.2 | |
8 | Is detailed company information provided in the instruction manual? | 87.2 | |
9 | Are all cautions clearly presented to the user? | 87.6 | |
10 | Are the operational procedures clearly presented to the user through icons and words? | 86.9 | |
Ease of result reading | 11 | Is your interpretation of the circle window the same as the medical staff’s result? | 95.2 |
12 | Is your interpretation of the control area the same as the medical staff’s result? | 99.7 |
We used a one-way analysis of variance (ANOVA) to test weight differences among specimens collected on different days. Kruskal-Wallis one-way ANOVA was used to test weight differences among specimens collected by different individuals. The statistical analysis of the two diagnostic test evaluation studies followed the statistical guidance on reporting results from studies evaluating diagnostic tests [
We evaluated the variation of specimen collection when using the toilet paper–based fecal specimen collection device (
Weight distribution and variation of fecal specimens that are collected among (A) different days and (B) different users.
An imprecision curve of the analytical reagents used in JustWipe was used to illustrate the analytical characteristics (
Analytical characteristics of the test reagents: (A) limit of detection, (B) positive probabilities for 5 and 15 µg/mL, and (C) reproducibility among trained (medical staff) or untrained users.
A comparison of the performance between JustWipe and a typical fecal occult blood test (O-tolidine–based test) was conducted using 70 clinical specimens collected in a tertiary referral hospital. The overall agreement was 82.9% (52/70); the positive agreement and negative agreement were 83.9% (26/31) and 82.1% (32/39), respectively (
Performance comparison between JustWipe and a typical fecal occult blood test, and between JustWipe and Hemoccult SENSA.
Comparison | Hospital fecal occult blood test | Hemoccult SENSA | |||||||||||
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Positive | Negative | Total | Positive | Negative | Total | ||||||
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Positive | 26 | 7 | 33 | 16 | 2 | 18 | ||||||
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Negative | 5 | 32 | 37 | 4 | 36 | 40 | ||||||
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Total | 31 | 39 | 70 | 20 | 38 | 58 | ||||||
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Estimate (95% CLa) | 83.9 (70.7, 97.1) | 82.1 (69.8, 94.3) | 82.9 (73.9, 91.9) | 80.0 (62.1, 80.0) | 94.7 (87.5, 102) | 89.7 (81.7, 97.7) |
a95% confidence limits calculated as (estimate – 2 standard error, estimate + 2 standard error).
The intended use of JustWipe is testing occult blood in the stool at home or at a point of care. Thus, we evaluated the performance of JustWipe when it was used as a point-of-care test according to the manufacturer’s instructions. The overall agreement was 89.7% (52/58); the positive agreement and negative agreement were 80.0% (16/20) and 94.7% (36/38), respectively (
Of the 58 volunteers, there were 32 (55.2%) women and 26 (44.9%) men. The average age of the volunteers was 59.1 (SD 12.7) years. We asked the volunteers to complete the questionnaire (12 questions included) after using JustWipe as a point-of-care test. We summarized the results of the questionnaire into three categories: information usefulness (Q1, Q2, Q3, Q4, and Q5), operational friendliness (Q6, Q7, Q8, Q9, and Q10), and ease of reading results (Q11 and Q12). In terms of information usefulness, average agreement percentages for Q1, Q2, Q3, Q11, and Q12 were 100%, 98.6%, 100%, 88.3%, and 93.8%, respectively. In the category of operational friendliness, average agreement percentages for Q6, Q7, Q8, Q9, and Q10 were 89%, 86.2%, 87.2%, 87.6%, and 86.9%, respectively. For the category of ease of reading results, Q11 had an average of 95.2% and Q12 had an average of 99.7%.
In this study, we developed a toilet paper–based point-of-care test (JustWipe) for the rapid detection of fecal occult blood. An ordinary buttocks-wiping move on the toilet was adapted as the mechanism of stool specimen collection. Specimen collection by buttocks-wiping was evaluated to be useful and stable. In addition, a set of test reagents was developed and characterized. We compared the performance of JustWipe with that of a typical fecal occult blood test in a central laboratory setting. Moreover, we also demonstrated the performance of JustWipe as a point-of-care test. Based on the toilet paper–based device, stool specimens can be collected with a regular buttocks-wiping move. A rapid test result is available within 60 seconds using the test reagents. An ordinary user can operate the test easily, rapidly, and with reproducibility. The ease of operation and reliability render the novel fecal occult blood test a promising tool for colorectal cancer screening.
Troublesome operation of stool specimen collection is considered one of the obstacles affecting participation in colorectal cancer screening [
The analytical evaluation of the test reagents used in JustWipe demonstrated several favorable characteristics, including high sensitivity, high repeatability, and high reproducibility. Low-concentration hemoglobin could be detected with minimal day-to-day variation (high repeatability) and person-to-person variation (high reproducibility). Regarding the analytical sensitivity of the test reagents, the test reagents were found to have adequate analytical sensitivity to detect occult fecal blood in colorectal cancer patients. In a population study including 5.8 million individuals, a hemoglobin concentration of approximately 20 µg/mL could detect colorectal cancer with a detection rate of 5.2% in men and 2.2% in females. The hemoglobin concentration for the colorectal cancer patients identified in that study was between 172.8 and 231 µg hemoglobin/g feces [
We validated JustWipe in the settings of a central laboratory and point of care. In both settings, JustWipe showed high agreement with typical test methods. In the setting of the central laboratory, both JustWipe and the comparative test (O-tolidine–based fecal occult blood test) were performed by medical staff. The positive agreement (83.9%) and negative agreement (82.1%) were quite balanced (
The major aim of designing JustWipe was to improve the usability of fecal occult blood testing. We assessed the usability of JustWipe using a questionnaire (
Although the volunteers from our trial in the point-of-care test setting would be representative of the target population with respect to the range of age, sampling bias could still exist in the validation setting for the point-of-care test trial. All volunteers were recruited from the urban region in northern Taiwan. The average age of the recruited volunteers in the point-of-care test was 59.1 (SD 12.7) years. The range of age was approximately the age of the target population for most cancer screening programs. In the majority of Europe, the colorectal cancer prevention program recommends screening for people above 50 years old [
We developed and validated a toilet paper–based point-of-care test for detecting fecal occult blood. The result showed that the toilet paper–based collection of fecal specimens was stable. The test reagents of the point-of-care test also showed high repeatability and reproducibility. The novel toilet paper–based point-of-care test revealed high agreement with the comparative methods in both central laboratory and point-of-care test settings. The usability evaluation of the point-of-care test showed high operation friendliness and high ease of reading results. The favorable characteristics render the proposed novel point-of-care test a promising colorectal cancer screening tool.
Repeatability for a longer period (20 days) for the analytical characteristics of the test reagents.
Qualitative test results for both methods in the central laboratory.
Qualitative test results for both methods in the point-of-care test setting.
Association between individual usability indicators and result discordancy. The table showed the contingency table for each question on recruited volunteers with discordance and concordance result.
Using the mobile device for interpretation of test results. The workflow demonstrates how to use a mobile phone to assist interpretation with artificial intelligence model prediction.
This table contains the demographic characteristics of age, gender, education, and occupation of the recruited volunteers.
analysis of variance
Clinical and Laboratory Standards Institutes
computed tomographic
This work was edited by American Journal Experts. This work was supported by Sigknow Biomedical Co Ltd (SCRPD2I0011) and Chang Gung Memorial Hospital (CMRPD2J0031-33).
H-YW conceptualized the study. H-YW and T-WL wrote the manuscript, analyzed the data, plotted the figures, and created the tables. S-BH and HCC performed the experiments. SY-HC and J-JL reviewed and edited the manuscript for important intellectual content. M-HW obtained funding and supervised the study. All authors discussed the results and revised the manuscript.
This work was supported by Sigknow Biomedical Co Ltd (SCRPD2I0011). S-BH and H-CC were the employees of the Sigknow Biomedical Co Ltd.