mkdir -p /home/daytona/workspace/hepb-trial && ls /home/daytona/workspace/hepb-t…

~/hepb-trial/generate_protocol.js

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// ─── Document Content ───────────────────────────────────────────────────────

const sections = [
  // ── TITLE PAGE ──
  gap(), gap(), gap(),
  centerPara('RESEARCH PROTOCOL', 36, true, '1F4E79'),
  gap(),
  centerPara('A Randomized Controlled Field Trial to Compare the Immunogenicity', 26, false, '2E4057'),
  centerPara('and Efficacy of a New Hepatitis B Vaccine versus the Existing', 26, false, '2E4057'),
  centerPara('Standard Hepatitis B Vaccine in the Community of Bommalaramaram', 26, false, '2E4057'),
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  twoColTable([
    ['Protocol Version', 'Version 1.0'],
    ['Protocol Date', 'July 2026'],
    ['Principal Investigator', '[Name], MBBS, MD (Community Medicine)'],
    ['Institution', 'Primary Health Centre, Bommalaramaram, Telangana'],
    ['Sponsor / Funding', '[Institution / Grant Body Name]'],
    ['CTRI Registration', 'Pending'],
    ['IEC Reference No.', 'Pending'],
    ['Target Completion', 'July 2027 (12 months)'],
  ]),
  gap(), gap(),
  pageBreak(),

  // ── TABLE OF CONTENTS ──
  heading1('TABLE OF CONTENTS'),
  body('1.  Background and Rationale'),
  body('2.  Objectives'),
  body('3.  Study Design'),
  body('4.  Study Population'),
  body('5.  Sample Size Calculation'),
  body('6.  Randomization and Blinding'),
  body('7.  Intervention'),
  body('8.  Data Collection Tools and Procedures'),
  body('9.  Follow-Up Schedule'),
  body('10. Outcome Measures'),
  body('11. Statistical Analysis Plan'),
  body('12. Ethical Considerations'),
  body('13. Safety Monitoring and Adverse Event Reporting'),
  body('14. Data Management and Quality Control'),
  body('15. Dissemination Plan'),
  body('16. Budget Estimate'),
  body('17. Timeline / Gantt Chart'),
  body('18. References'),
  body('Annexures: Informed Consent Form, Data Collection Proforma, Vaccine Efficacy Formula'),
  pageBreak(),

  // ── SECTION 1 ──
  heading1('1. Background and Rationale'),
  heading2('1.1 Global Burden of Hepatitis B'),
  body('Hepatitis B (HBV) infection remains a major global public health problem. The World Health Organization (WHO) estimates that approximately 296 million people are living with chronic HBV infection worldwide, with 1.5 million new infections occurring annually. HBV is the leading cause of cirrhosis and hepatocellular carcinoma, responsible for an estimated 820,000 deaths per year.'),
  gap(),
  heading2('1.2 Burden in India'),
  body('India is categorized as an intermediate-to-high endemic zone for HBV, with a HBsAg seroprevalence ranging from 2-8% in the general population. The disease imposes a substantial burden on healthcare resources, particularly in rural and peri-urban communities served by Primary Health Centres (PHCs). During internship postings at the PHC of Bommalaramaram, a significant caseload of Hepatitis B was observed, highlighting the urgent need for effective preventive strategies.'),
  gap(),
  heading2('1.3 Current Hepatitis B Vaccines'),
  body('The recombinant DNA-derived Hepatitis B vaccine (HBsAg-based) has been the cornerstone of prevention since the 1980s and is included in India\'s Universal Immunization Programme (UIP). The standard 3-dose regimen (0, 1, 6 months) achieves seroprotective anti-HBs titres (>=10 mIU/mL) in approximately 90-95% of healthy adults. However, 5-10% of recipients remain non-responders, and waning immunity over time is a concern.'),
  gap(),
  heading2('1.4 The New Vaccine'),
  body('A newer generation Hepatitis B vaccine has been developed claiming superior protection rates through enhanced immunogenicity - potentially via improved adjuvant systems (e.g., AS04), higher antigen content, or novel delivery platforms. Preliminary data from phase II trials suggest protection rates of 97-99%. However, real-world comparative data from field settings in India, particularly in communities like Bommalaramaram, are lacking.'),
  gap(),
  heading2('1.5 Rationale for This Study'),
  body('Before recommending adoption of the new vaccine into the PHC immunization schedule, rigorous head-to-head comparison with the existing vaccine under field conditions is required. A Randomized Controlled Field Trial (RCFT) is the most scientifically valid design for this purpose, as it minimizes bias through randomization, allows direct comparison, and generates population-specific efficacy data applicable to this community.'),
  pageBreak(),

  // ── SECTION 2 ──
  heading1('2. Objectives'),
  heading2('2.1 Primary Objective'),
  body('To compare the seroconversion rate (anti-HBs titre >= 10 mIU/mL) of the new Hepatitis B vaccine versus the existing standard Hepatitis B vaccine in the community of Bommalaramaram at 1 month after completion of the 3-dose schedule.'),
  gap(),
  heading2('2.2 Secondary Objectives'),
  bullet('To compare the geometric mean titres (GMT) of anti-HBs antibody between the two groups.'),
  bullet('To compare the incidence of clinical and subclinical Hepatitis B infection over 12 months follow-up.'),
  bullet('To assess and compare the safety profile (local and systemic adverse events) of the two vaccines.'),
  bullet('To determine vaccine efficacy (VE) using the formula: VE = (ARU - ARE) / ARU x 100.'),
  bullet('To identify predictors of non-response (age, sex, BMI, immune status).'),
  pageBreak(),

  // ── SECTION 3 ──
  heading1('3. Study Design'),
  twoColTable([
    ['Study Type', 'Randomized Controlled Field Trial (RCFT) - Experimental Study'],
    ['Design', 'Parallel-group, double-blind, active-controlled'],
    ['Setting', 'Community of Bommalaramaram, Yadadri Bhongir District, Telangana, India'],
    ['Duration', '12 months (6 months recruitment + vaccination + 6 months follow-up)'],
    ['Allocation Ratio', '1:1 (equal allocation to both arms)'],
    ['Blinding', 'Double-blind: participants and outcome assessors blinded to allocation'],
    ['Primary Endpoint', 'Seroconversion at 1 month post 3rd dose'],
  ]),
  gap(),
  body('The RCT is the gold standard (No.1 method) for evaluating new vaccines or therapies, as stated in Park\'s Textbook of Preventive and Social Medicine. This design is classified as a Field Trial because: (i) subjects are healthy individuals at risk, (ii) the intervention is preventive (vaccine), and (iii) the setting is a community field location, not a hospital.'),
  pageBreak(),

  // ── SECTION 4 ──
  heading1('4. Study Population'),
  heading2('4.1 Reference Population'),
  body('All residents of Bommalaramaram who are susceptible to Hepatitis B infection (i.e., HBsAg-negative and anti-HBs negative).'),
  gap(),
  heading2('4.2 Inclusion Criteria'),
  bullet('Age 1-40 years (both sexes)'),
  bullet('HBsAg negative on ELISA testing'),
  bullet('Anti-HBs titre < 10 mIU/mL (i.e., not previously immune)'),
  bullet('No prior Hepatitis B vaccination history'),
  bullet('Willing to provide written informed consent (or parental/guardian consent for minors)'),
  bullet('Resident of Bommalaramaram for >= 6 months and intending to remain for study duration'),
  gap(),
  heading2('4.3 Exclusion Criteria'),
  bullet('Known immunocompromised state (HIV, on steroids, chemotherapy, organ transplant)'),
  bullet('Pregnancy or breastfeeding (will be included only after delivery per discretion)'),
  bullet('Known hypersensitivity to any vaccine component'),
  bullet('Serious chronic illness (CKD, liver disease, malignancy)'),
  bullet('Received any live or inactivated vaccine within the past 4 weeks'),
  bullet('Unwilling or unable to comply with follow-up schedule'),
  pageBreak(),

  // ── SECTION 5 ──
  heading1('5. Sample Size Calculation'),
  body('Sample size is calculated using the formula for comparison of two proportions:'),
  gap(),
  body('n = [Z(alpha/2) + Z(beta)]^2 x [P1(1-P1) + P2(1-P2)] / (P1 - P2)^2', false, true, '1F4E79'),
  gap(),
  body('Assumptions:'),
  twoColTable([
    ['Protection rate - Existing vaccine (P1)', '92% (0.92)'],
    ['Protection rate - New vaccine (P2)', '98% (0.98)'],
    ['Expected difference (d)', '6% (0.06)'],
    ['Level of significance (alpha)', '5% (two-tailed, Z = 1.96)'],
    ['Power (1 - beta)', '80% (Z = 0.842)'],
    ['Calculated n (per group)', '~280'],
    ['Attrition allowance (+15%)', '~322 per group'],
    ['Total sample size', '~644 participants (322 per arm)'],
  ]),
  gap(),
  body('A conservative 15% attrition allowance has been built in to account for dropouts, loss to follow-up, and protocol deviations expected in a community field setting.'),
  pageBreak(),

  // ── SECTION 6 ──
  heading1('6. Randomization and Blinding'),
  heading2('6.1 Randomization'),
  body('Computer-generated randomization will be used (using sealed envelope method or SNOSE - Sequentially Numbered Opaque Sealed Envelopes). A statistician not involved in the trial will generate the sequence using a random number generator. Permuted block randomization (block size 4 or 6) will be used to ensure balanced allocation throughout recruitment.'),
  gap(),
  heading2('6.2 Allocation Concealment'),
  body('Vaccine vials will be pre-coded (A or B) by the trial pharmacist, who will not participate in clinical assessment. Field workers will administer whichever coded vial is assigned per the randomization list, maintaining allocation concealment.'),
  gap(),
  heading2('6.3 Blinding'),
  body('Double-blinding will be maintained:'),
  bullet('Participants: will not know which vaccine they received'),
  bullet('Outcome assessors / laboratory personnel: will be blinded to group assignment when measuring anti-HBs titres'),
  body('The principal investigator and data analyst will remain blinded until primary endpoint data collection is complete. Unblinding will only occur after database lock.'),
  pageBreak(),

  // ── SECTION 7 ──
  heading1('7. Intervention'),
  heading2('7.1 Control Arm - Existing Standard Vaccine'),
  twoColTable([
    ['Vaccine', 'Recombinant Hepatitis B Vaccine (HBsAg, 20 mcg/1 mL for adults; 10 mcg/0.5 mL for children <10 yr)'],
    ['Route', 'Intramuscular, deltoid (anterolateral thigh for children)'],
    ['Dose', '1 mL (adult) / 0.5 mL (paediatric)'],
    ['Schedule', '0, 1, 6 months (3-dose regimen)'],
    ['Cold chain', '2-8 degrees Celsius'],
  ]),
  gap(),
  heading2('7.2 Experimental Arm - New Vaccine'),
  twoColTable([
    ['Vaccine', 'New-generation Hepatitis B Vaccine (exact brand/formulation to be specified in final protocol)'],
    ['Route', 'Intramuscular, deltoid (anterolateral thigh for children)'],
    ['Dose', 'Per manufacturer recommendation'],
    ['Schedule', '0, 1, 6 months (3-dose regimen) - same schedule'],
    ['Cold chain', '2-8 degrees Celsius'],
  ]),
  gap(),
  body('Both vaccines will be stored and transported following WHO cold chain guidelines. Any cold chain break will be documented and the affected vials will be discarded.'),
  pageBreak(),

  // ── SECTION 8 ──
  heading1('8. Data Collection Tools and Procedures'),
  heading2('8.1 Baseline Assessment (Day 0 - before 1st dose)'),
  bullet('Sociodemographic details: Name, age, sex, address, contact number'),
  bullet('Medical history: Prior illnesses, medications, vaccination history'),
  bullet('Physical examination: Weight, height, BMI, blood pressure'),
  bullet('Baseline blood sample: HBsAg (ELISA), anti-HBs titre (ELISA), anti-HBc (to confirm susceptibility), CBC, LFT'),
  gap(),
  heading2('8.2 Data Collection Instrument'),
  body('A pre-tested, structured data collection proforma (Annexure 3) will be used. The proforma will include:'),
  bullet('Part A: Sociodemographic and baseline data'),
  bullet('Part B: Vaccination record and cold chain documentation'),
  bullet('Part C: Adverse event monitoring (local and systemic reactions at 30 min, 24h, 48h, 7 days post each dose)'),
  bullet('Part D: Follow-up serology results'),
  gap(),
  heading2('8.3 Laboratory Methods'),
  twoColTable([
    ['Anti-HBs titre', 'Quantitative ELISA (cut-off: >= 10 mIU/mL = seroprotection)'],
    ['HBsAg', 'ELISA (3rd generation)'],
    ['Anti-HBc IgM', 'ELISA (for incident infection detection)'],
    ['Geometric Mean Titre (GMT)', 'Calculated from log-transformed titres'],
    ['Laboratory', 'Accredited reference laboratory, Hyderabad'],
  ]),
  pageBreak(),

  // ── SECTION 9 ──
  heading1('9. Follow-Up Schedule'),
  multiColTable(
    ['Visit', 'Timing', 'Activity'],
    [
      ['Visit 0 (Enrolment)', 'Day 0 (Month 0)', 'Consent, baseline serology, Dose 1 administration'],
      ['Visit 1', 'Month 1', 'Dose 2 administration, adverse event review'],
      ['Visit 2', 'Month 6', 'Dose 3 administration, adverse event review'],
      ['Visit 3 (Primary endpoint)', 'Month 7 (1 month post Dose 3)', 'Blood sample: anti-HBs titre measurement'],
      ['Visit 4', 'Month 9', 'Clinical review, any HBV symptoms/signs assessment'],
      ['Visit 5 (Final)', 'Month 12', 'Final serology (anti-HBs, HBsAg, anti-HBc IgM), study completion'],
    ]
  ),
  gap(),
  body('Participants who miss a visit will be contacted by telephone within 48 hours. Those lost to follow-up will be documented and included in the intention-to-treat (ITT) analysis.'),
  pageBreak(),

  // ── SECTION 10 ──
  heading1('10. Outcome Measures'),
  heading2('10.1 Primary Outcome'),
  body('Seroconversion rate: Proportion of participants achieving anti-HBs titre >= 10 mIU/mL at 1 month post 3rd dose (Month 7) in each group.'),
  gap(),
  heading2('10.2 Secondary Outcomes'),
  bullet('Geometric Mean Titre (GMT) of anti-HBs at Month 7 and Month 12'),
  bullet('Incidence of Hepatitis B infection (clinical or serological) over 12 months'),
  bullet('Vaccine Efficacy (VE) = [(ARU - ARE) / ARU] x 100, where ARU = attack rate in control, ARE = attack rate in experimental group'),
  bullet('Local adverse events: Pain, redness, swelling at injection site (within 7 days of each dose)'),
  bullet('Systemic adverse events: Fever (>=37.5C), malaise, fatigue (within 7 days of each dose)'),
  bullet('Serious Adverse Events (SAEs): Any hospitalization, life-threatening event, or death (throughout study)'),
  gap(),
  heading2('10.3 Outcome Adjudication'),
  body('All outcomes will be assessed by a trained outcome assessor blinded to group allocation. All SAEs will be reviewed by the Data Safety Monitoring Board (DSMB).'),
  pageBreak(),

  // ── SECTION 11 ──
  heading1('11. Statistical Analysis Plan'),
  heading2('11.1 Analysis Populations'),
  bullet('Intention-to-Treat (ITT): All randomized participants who received at least one dose'),
  bullet('Per-Protocol (PP): Participants who completed all 3 doses and attended Month 7 visit'),
  gap(),
  heading2('11.2 Primary Analysis'),
  body('Seroconversion rates in the two groups will be compared using Chi-square test (or Fisher\'s exact test if expected cell frequency <5). Results will be expressed as:'),
  bullet('Relative Risk (RR) with 95% Confidence Interval'),
  bullet('Number Needed to Vaccinate (NNV) = 1 / (Seroconversion rate new - Seroconversion rate existing)'),
  gap(),
  heading2('11.3 Secondary Analysis'),
  bullet('GMT comparison: Independent samples t-test on log-transformed titres'),
  bullet('Incidence rates: Kaplan-Meier survival analysis with Log-rank test'),
  bullet('Vaccine Efficacy: Calculated with 95% CI using the Greenland and Robins method'),
  bullet('Adverse events: Chi-square test for proportions'),
  bullet('Predictors of non-response: Logistic regression (multivariate)'),
  gap(),
  body('Statistical significance will be set at p < 0.05 (two-tailed). All analysis will be performed using SPSS version 25 or STATA 16.'),
  pageBreak(),

  // ── SECTION 12 ──
  heading1('12. Ethical Considerations'),
  heading2('12.1 Ethical Approval'),
  body('This protocol will be submitted to the Institutional Ethics Committee (IEC) of the concerned institution for review and approval before commencement. The trial will be registered with the Clinical Trials Registry of India (CTRI).'),
  gap(),
  heading2('12.2 Informed Consent'),
  body('Written informed consent will be obtained from all participants (or parent/guardian for minors below 18 years) prior to enrolment. The consent form will be provided in English and Telugu. Participants will be informed of:'),
  bullet('Purpose and procedures of the study'),
  bullet('Risks and potential benefits'),
  bullet('Right to withdraw at any time without penalty'),
  bullet('Confidentiality of data'),
  bullet('Contact details of the PI and IEC for queries'),
  gap(),
  heading2('12.3 Risk-Benefit Assessment'),
  body('Both groups receive an active Hepatitis B vaccine. No participant will receive a placebo (saline injection), thus the ethical concern of withholding protection is eliminated. The risk is limited to minor injection-site reactions and rare systemic adverse events, consistent with established vaccine safety profiles.'),
  gap(),
  heading2('12.4 Confidentiality'),
  body('All data will be anonymized. Participant identity will be protected using unique identification codes. Paper records will be stored in locked cabinets accessible only to authorized study personnel. Electronic data will be password-protected.'),
  gap(),
  heading2('12.5 Declaration of Helsinki'),
  body('The study will be conducted in full conformity with the Declaration of Helsinki (2013 revision), ICMR National Ethical Guidelines for Biomedical and Health Research Involving Human Participants (2017), and applicable Indian regulatory requirements (CDSCO/New Drugs and Clinical Trials Rules 2019).'),
  pageBreak(),

  // ── SECTION 13 ──
  heading1('13. Safety Monitoring and Adverse Event Reporting'),
  body('A Data Safety Monitoring Board (DSMB) comprising 3 independent experts (one clinician, one statistician, one ethicist) will review safety data every 3 months. Stopping rules will be pre-specified: if the rate of SAEs exceeds pre-defined thresholds, the DSMB may recommend suspension or early termination.'),
  gap(),
  body('Adverse events will be graded per WHO/CIOMS scale:'),
  multiColTable(
    ['Grade', 'Description', 'Action'],
    [
      ['Grade 1 (Mild)', 'Transient, no intervention needed', 'Document and monitor'],
      ['Grade 2 (Moderate)', 'Some limitation in activity, minimal intervention', 'Document, symptomatic treatment'],
      ['Grade 3 (Severe)', 'Marked limitation, medical intervention needed', 'Immediate report to PI and DSMB'],
      ['Grade 4 (Life-threatening)', 'Immediate risk to life', 'Unblind, emergency care, DSMB, IEC, CDSCO notification within 24h'],
    ]
  ),
  pageBreak(),

  // ── SECTION 14 ──
  heading1('14. Data Management and Quality Control'),
  bullet('All data will be entered into a password-protected electronic database (Epi Info 7 / REDCap)'),
  bullet('Double data entry will be performed by two independent data entry operators'),
  bullet('Range checks, logic checks, and consistency checks will be programmed into the database'),
  bullet('Source document verification will be conducted by a study monitor every 2 months'),
  bullet('All deviations from the protocol will be documented and reported to the IEC'),
  bullet('Data will be backed up on an encrypted external server weekly'),
  pageBreak(),

  // ── SECTION 15 ──
  heading1('15. Dissemination Plan'),
  bullet('Results will be published in a peer-reviewed journal (e.g., Indian Journal of Community Medicine, Vaccine)'),
  bullet('Findings will be presented at national and state-level community medicine conferences'),
  bullet('A summary report will be shared with the District Health Officer, Yadadri Bhongir District, for policy consideration'),
  bullet('Community feedback meeting will be held in Bommalaramaram at study completion'),
  pageBreak(),

  // ── SECTION 16 ──
  heading1('16. Budget Estimate'),
  multiColTable(
    ['Item', 'Details', 'Estimated Cost (INR)'],
    [
      ['Vaccine (New)', '322 participants x 3 doses', '96,600'],
      ['Vaccine (Existing)', '322 participants x 3 doses', '32,200'],
      ['Laboratory (Serology)', '644 participants x 3 time points', '1,93,200'],
      ['Personnel (Field workers x 3)', '12 months x salaries', '3,60,000'],
      ['Stationery and proformas', 'Printing, data entry', '15,000'],
      ['Cold chain equipment', 'Ice boxes, thermometers', '25,000'],
      ['Data management (REDCap)', 'Software, IT support', '20,000'],
      ['Miscellaneous (transport, etc.)', '-', '30,000'],
      ['TOTAL', '', 'Approx. INR 7,72,000'],
    ]
  ),
  pageBreak(),

  // ── SECTION 17 ──
  heading1('17. Timeline (Gantt Chart)'),
  multiColTable(
    ['Activity', 'Month 1', 'Month 2', 'Month 3-4', 'Month 5-6', 'Month 7', 'Month 8-12'],
    [
      ['Protocol finalization & IEC submission', 'X', 'X', '', '', '', ''],
      ['CTRI registration', '', 'X', '', '', '', ''],
      ['Pilot study / pre-testing', '', 'X', '', '', '', ''],
      ['Community sensitization & baseline survey', '', '', 'X', 'X', '', ''],
      ['Enrolment and Dose 1 (Month 0)', '', '', 'X', 'X', '', ''],
      ['Dose 2 (Month 1 post enrolment)', '', '', '', 'X', 'X', ''],
      ['Dose 3 (Month 6 post enrolment)', '', '', '', '', '', 'X'],
      ['Primary endpoint blood sampling (Month 7)', '', '', '', '', '', 'X'],
      ['Follow-up visits (Months 9, 12)', '', '', '', '', '', 'X'],
      ['Data analysis and report writing', '', '', '', '', '', 'X'],
      ['Dissemination of results', '', '', '', '', '', 'X'],
    ]
  ),
  pageBreak(),

  // ── SECTION 18 ──
  heading1('18. References'),
  body('1. World Health Organization. Hepatitis B Fact Sheet. WHO, 2023. Available at: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b'),
  body('2. Park K. Park\'s Textbook of Preventive and Social Medicine. 26th ed. Jabalpur: Banarsidas Bhanot Publishers; 2021. p. 94.'),
  body('3. Ministry of Health and Family Welfare, Government of India. Universal Immunization Programme. New Delhi: MoHFW; 2023.'),
  body('4. ICMR. National Ethical Guidelines for Biomedical and Health Research Involving Human Participants. New Delhi: ICMR; 2017.'),
  body('5. Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. WMA, 2013.'),
  body('6. New Drugs and Clinical Trials Rules. Ministry of Health and Family Welfare, Govt. of India; 2019.'),
  pageBreak(),

  // ── ANNEXURE A ──
  heading1('Annexure 1: Informed Consent Form (English)'),
  body('TITLE OF STUDY: A Randomized Controlled Field Trial to Compare the Immunogenicity and Efficacy of a New Hepatitis B Vaccine versus the Existing Standard Hepatitis B Vaccine in the Community of Bommalaramaram', false, true),
  gap(),
  body('I, _____________________________________, son/daughter/wife of _________________________, residing at __________________________________________, have been explained in my own language about the purpose, procedures, risks, and benefits of the above-mentioned study by the principal investigator.'),
  gap(),
  body('I understand that:'),
  bullet('My participation is completely voluntary.'),
  bullet('I may withdraw from the study at any time without giving any reason and without affecting my medical care.'),
  bullet('My identity will remain confidential and my personal data will be used only for this research.'),
  bullet('I have had sufficient time to consider my participation and ask any questions, which have been satisfactorily answered.'),
  bullet('I will receive 3 doses of a Hepatitis B vaccine and 3 blood samples will be collected over 12 months.'),
  gap(),
  body('Signature / Thumb Impression of Participant: _____________________   Date: ____________'),
  gap(),
  body('Signature of Witness: _____________________   Date: ____________'),
  gap(),
  body('Signature of Principal Investigator: _____________________   Date: ____________'),
  pageBreak(),

  // ── ANNEXURE B ──
  heading1('Annexure 2: Vaccine Efficacy Formula'),
  body('Vaccine Efficacy (VE) is calculated as:', false, false),
  gap(),
  body('VE (%) = [(ARU - ARE) / ARU] x 100', true, false, '1F4E79'),
  gap(),
  body('Where:'),
  bullet('ARU = Attack Rate in Unvaccinated (control) group = No. of HBV cases in control / Total in control group'),
  bullet('ARE = Attack Rate in (Experimentally) vaccinated group = No. of HBV cases in experimental / Total in experimental group'),
  gap(),
  body('Example: If ARU = 8% and ARE = 2%, then VE = [(0.08 - 0.02) / 0.08] x 100 = 75%'),
  gap(),
  body('A VE of >=50% with lower bound of 95% CI >30% is generally considered the threshold for vaccine approval by WHO.'),
  pageBreak(),

  // ── ANNEXURE C ──
  heading1('Annexure 3: Data Collection Proforma (Summary)'),
  body('Unique ID: _____________    Date: _____________    Village/Ward: _____________'),
  gap(),
  heading2('Part A - Sociodemographic Details'),
  multiColTable(
    ['Variable', 'Details'],
    [
      ['Name', ''],
      ['Age (years)', ''],
      ['Sex', 'M / F / Other'],
      ['Education', 'Illiterate / Primary / Secondary / Graduate+'],
      ['Occupation', ''],
      ['Family income (monthly, INR)', ''],
    ]
  ),
  gap(),
  heading2('Part B - Baseline Serology'),
  multiColTable(
    ['Test', 'Result', 'Date of Sample'],
    [
      ['HBsAg (ELISA)', 'Positive / Negative', ''],
      ['Anti-HBs (mIU/mL)', '', ''],
      ['Anti-HBc IgM', 'Positive / Negative', ''],
    ]
  ),
  gap(),
  heading2('Part C - Vaccination Record'),
  multiColTable(
    ['Dose', 'Date', 'Vaccine Code (A/B)', 'Batch No.', 'Administered By'],
    [
      ['Dose 1 (Month 0)', '', '', '', ''],
      ['Dose 2 (Month 1)', '', '', '', ''],
      ['Dose 3 (Month 6)', '', '', '', ''],
    ]
  ),
  gap(),
  heading2('Part D - Follow-up Serology'),
  multiColTable(
    ['Visit', 'Date', 'Anti-HBs (mIU/mL)', 'HBsAg', 'Remarks'],
    [
      ['Month 7 (Primary)', '', '', '', ''],
      ['Month 12 (Final)', '', '', '', ''],
    ]
  ),
];

// ─── Build and Save Document ─────────────────────────────────────────────────

const doc = new Document({
  creator: 'Research Protocol Generator',
  title: 'Hepatitis B Vaccine Field Trial Protocol',
  description: 'RCT Protocol for Hep B vaccine comparison at Bommalaramaram',
  styles: {
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        id: 'Heading1',
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        paragraph: { spacing: { before: 400, after: 120 } },
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        paragraph: { spacing: { before: 160, after: 60 } },
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  sections: [
    {
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            right: convertInchesToTwip(1),
            bottom: convertInchesToTwip(1),
            left: convertInchesToTwip(1.25),
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Packer.toBuffer(doc).then(buffer => {
  fs.writeFileSync('/home/daytona/workspace/hepb-trial/HepB_Vaccine_Trial_Protocol.docx', buffer);
  console.log('Document created successfully.');
});

cd /home/daytona/workspace/hepb-trial && node generate_protocol.js 2>&1

python /home/daytona/skills/docx/scripts/office/validate.py /home/daytona/worksp…

ls -lh /home/daytona/workspace/hepb-trial/ && python3 -c "import zipfile; z = zi…

pandoc /home/daytona/workspace/hepb-trial/HepB_Vaccine_Trial_Protocol.docx -t pl…