18 Haz Clinical Trial Study Protocol
Protocol Title: A Prospective, Double-Blind Diagnostic Accuracy Study of the Parola Phenomenon in Patients with Symptomatic Hemorrhoids
Protocol Number: S1 (Supplementary Protocol 1)
Protocol Version: 1.0
Date: Oct 14, 2021
Investigators:
Cem Atabiner, Nimsai Academia Principal Investigator
Nimsai Academia Anal Fissure-Hemorrhoid Research Team
Affiliation:
Nimsai Academia, Türkiye
Corresponding Investigator:
Cem Atabiner, info@nimsai.com
1. Introduction and Rationale
The War-Drill Model proposes that hemorrhoids manifest through two distinct mechanisms: War Mode (driven by underlying pathologies) and Drill Mode (triggered by transient hormonal fluctuations). Accurate differentiation between these modes is crucial for targeted therapeutic strategies. The Parola Phenomenon, a novel clinical tool, is hypothesized to provide a simple and rapid method for this differentiation. This study aims to prospectively evaluate the diagnostic accuracy of the Parola Phenomenon, providing empirical validation for its clinical utility within the War-Drill Model framework.
2. Study Objectives
2.1. Primary Objective:
To assess the diagnostic accuracy (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], and overall accuracy) of the Parola Phenomenon in differentiating between War Mode and Drill Mode hemorrhoids.
2.2. Secondary Objectives:
To evaluate the association between Parola Phenomenon responses and established diagnostic criteria (clinical history, endoscopic findings, histopathological examination).
To assess the consistency of Parola Phenomenon diagnostic accuracy across different age and gender subgroups.
3. Study Design
This is a prospective, double-blind diagnostic accuracy study. Participants were assessed for the Parola Phenomenon, and their hemorrhoid mode (War or Drill) was independently confirmed using a comprehensive diagnostic standard (composite reference standard).
4. Study Population
4.1. Inclusion Criteria:
Age: 18-70 years.
Sex: Male or female.
Symptomatic hemorrhoids (≥3 months duration) confirmed by anoscopic or clinical evaluation.
Willingness and ability to provide written informed consent.
4.2. Exclusion Criteria:
Confirmed anorectal malignancy.
Acutely thrombosed external hemorrhoids.
Pregnancy or lactation.
Any medical condition that, in the opinion of the investigator, might interfere with the study procedures or compromise patient safety.
4.3. Recruitment and Setting:
200 patients were enrolled from Nimsai Academia’s affiliated clinics. Recruitment took place from Oct 14, 2021to Nov 14, 2021.
5. Diagnostic Procedures
5.1. Parola Phenomenon Assessment:
A standardized question was posed to each participant: “Does voluntary contraction of your anal sphincter significantly increase the sensation of throbbing or discomfort in your anal area?” (Yes/No response for Parola Positive/Negative). This assessment was performed by a blinded clinician.
5.2. Confirmation of Mode (Reference Standard):
The definitive diagnosis of War Mode or Drill Mode was independently established through a comprehensive reference standard, including:
Detailed Clinical History: Comprehensive patient interview to assess symptom patterns, associated systemic conditions, and hormonal influences.
Endoscopic Findings: Anoscopic and/or colonoscopic examination to identify underlying anorectal pathologies (e.g., anal fissure, fistula, polyps, proctitis, Crohn’s disease, ulcerative colitis, diverticulitis, rectocele, IBS, portal hypertension, pelvic congestion, etc.).
Histopathological Examination: Biopsy samples were collected from suspicious lesions (if present) for histopathological confirmation of underlying pathologies.
5.3. Blinding:
This was a double-blind study. The clinician assessing the Parola Phenomenon was blinded to the results of the comprehensive mode confirmation, and the clinicians/pathologists performing the comprehensive mode confirmation were blinded to the Parola Phenomenon response.
6. Outcome Measures
6.1. Primary Outcome:
Diagnostic Accuracy: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy of the Parola Phenomenon (Yes/No response) against the independently confirmed War Mode or Drill Mode diagnosis.
7. Sample Size Justification
A sample size of 200 participants was deemed sufficient to estimate the sensitivity and specificity of the Parola Phenomenon with a desired level of precision. Based on an anticipated sensitivity of 94% and specificity of 91% (as observed in initial pilot or exploratory analyses), a sample size of 200 provides a 95% confidence interval width of approximately ±5% for sensitivity (ranging from 89% to 99%) and ±6% for specificity (ranging from 85% to 97%), offering robust evidence for its high diagnostic performance.
8. Data Collection and Management
Data were collected using standardized questionnaires and clinical examination forms. All data were anonymized prior to analysis and stored securely on a password-protected server. Data quality control measures were implemented to ensure accuracy and completeness.
9. Statistical Analysis Plan
Diagnostic Accuracy Metrics: Sensitivity, specificity, PPV, NPV, and overall accuracy will be calculated with 95% confidence intervals.
Association Analysis: Logistic regression will be used to assess the association between Parola Phenomenon responses and the independently confirmed modes.
Subgroup Analysis: Accuracy will be assessed across age and gender subgroups descriptively.
Software: Statistical analyses will be performed using R statistical software v4.5.1
10. Ethical Considerations
This study adhered to the Declaration of Helsinki principles. The protocol was approved by the Nimsai Academia Ethics Committee (Protocol S1, Approval Date: October 10, 2021). Written informed consent was obtained from all participants prior to any study procedures.
11. Dissemination Plan
The findings of this study will be submitted for publication in peer-reviewed medical journals and presented at relevant scientific conferences. Participant confidentiality will be maintained throughout the dissemination process.
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