Health Technology Assessment: Point of Care Test Kit

Hemophilia A and von Willebrand Disease

• Most common hereditary bleeding disorders.
• Global prevalence: Approximately 1 in 1,000 individuals.
• Hemophilia A:
  • Prevalence: Approximately 1 in 5,000 males or 1 in 10,000 overall.
  • Estimated cases in India: 140,000.
• von Willebrand disease:
  • Prevalence: Approximately 1% of the general population.
  • Estimated cases in India: Approximately one-third of total cases.
• Registered cases with Hemophilia Federation of India: Approximately 27,000.
• Significant gap between diagnosed and prevalent cases.

Challenges in Diagnosis

• Expensive and time-consuming diagnostic methods.
• Limited comprehensive diagnostic facilities in India.
• Coagulation screening facilities unavailable in many district hospitals and medical colleges.
• Many labs lack facilities to diagnose von Willebrand disease, leading to misdiagnosis as hemophilia A.
• Von Willebrand factor is a carrier for hemophilia A protein.
• High rates of underdiagnosis and incorrect treatment.

Current Standard of Care

• Initial screening: CBC (complete blood count), prothrombin time (PT), and activated partial thromboplastin time (APTT).
• Suspect hemophilia A and von Willebrand disease if normal PT and prolonged/abnormal APTT.
• Confirmatory tests:
  • Cost: Rupees 2,000 to 9,000 across labs in India.
  • Require specialized lab equipment, technical expertise, costly reagents, and fresh blood samples.
• Factor assays are available at limited public health facilities (centers of excellence).
• Time-intensive and expensive procedures.

Point of Care Test Kit

• Developed by ICMR, National Institute of Immunohematology, Mumbai.
• World's first point of care test for diagnosing hemophilia A and von Willebrand disease.
• Manufactured by Bart Biotic India Private Limited.
• Technology: Natural flow immuno-based technology.
• Results in 10 minutes, without advanced expertise or infrastructure.
• Detects factor eight antigen and von Willebrand factor antigen using minimal blood plasma sample.
• Sensitivity: $98.12 \%$.
• Specificity: $98.27 \%$.
• Validated across five leading Indian medical centers.
• Tested for stability for 18 months at 4 degrees Celsius.
• Price:
  • Hemophilia A kit: Rupees 250.
  • von Willebrand disease kit: Rupees 200.
  • Combined cost: Rupees 450.
• Portable and feasible for use at primary health care facilities.
• Facilitates early and accurate qualitative differential diagnosis, enabling timely treatment and referral.

Health Technology Assessment (HTA)

• PICO (Population, Intervention, Comparator, Outcome):
  • Population: Individuals aged 0-40 years presenting with bleeding disorder symptoms.
  • Intervention: Point of care test kit (two scenarios).
  • Comparator: Standard of care test (initial screening followed by confirmatory tests).
  • Outcomes: cost per case tested/detected, number of cases detected, additional cases detected, budget impact.
• Objective: Assess cost per case and budget impact of the point of care test kit compared to standard of care.
• Method: Cost analysis comparing point of care test kit against standard diagnostic method.
• Data: Secondary data (health system cost) and primary health system costing (ICMR, NIIH).

Decision Tree

• Intervention:
  • Scenario 1: All individuals tested using the point of care test kit.
  • Scenario 2: Initial screening with CBC, PT, APTT; point of care test only if APTT is abnormal/prolonged.
• Comparator: Standard of care test with initial screening (CBC, PT, APTT).
  • If APTT prolonged/abnormal: Factor assay (hemophilia A) and immunoturbidometry (von Willebrand factor).
• Outcomes:
  • Positive for hemophilia A or von Willebrand disease.
  • Negative (suggestive of other bleeding disorder).
• Perspective: Public health system perspective.

Results

• Number of Cases Detected:
  • Point of care test (both scenarios) detected more additional cases compared to standard of care.
  • Hemophilia A: Additional cases detected using point of care test ranged from 67,000 to 79,000 more than standard of care.
  • von Willebrand disease: Average 83,000 additional cases detected.
• Cost Analysis:
  • Cost per case tested: 3.5 times lower with point of care test.
  • Cost per case detected: 7 times lower with point of care test.

Budget Impact Analysis

• Conducted at 60%, 80%, and 50% coverage of the population.
• Budget for intervention (point of care test) is lower than standard of care in all scenarios.
• Significant cost savings with point of care test implementation (reducing system cost by almost three times).

Advantages of Point of Care Test

• Significant reduction in cost and time.
• Accurate diagnosis due to high sensitivity and specificity.
• Available at all levels of care (unlike current limitations).
• Early detection, facilitating early treatment initiation.

Policy Implications

• Improved access to diagnostics.
• Reduction in out-of-pocket expenditure, decreasing financial burden on families.
• Substantial cost savings for the health system.

Recommendations

• Point of care test kit suitable for qualitative diagnosis of hemophilia A and von Willebrand disease.
• Factor assay needed for quantitative analysis (severity, factor requirement).
• Kit should be available across all levels of public health care systems.
• Formulate standard treatment workflow for diagnosis and referral.

Remarks from Dr. Rucha Patil & Dr. Bipin Kulkarni

• Only 27,000 hemophilia patients are registered in India till date whereas the second most populated country should have more.
• Hemophilia and von Willebrand disease patients are underdiagnosed.
• Kit cost: Around 500 rupees compared to 1,000-7,000 rupees for gold standard tests.
• Can be used anywhere with just a finger prick sample.
• Detection limit: Can only detect 5% and below for severe cases and will miss out mild to moderate cases.
• Lack of diagnostic facilities is a major reason for underdiagnosis.
• Kits can identify severe hemophilia A and rule out von Willebrand disease simultaneously.
• No trained technicians required.

Questions and Answers

• Cold Chain Maintenance:
  • Can be kept at room temperature for six months if controlled room temperature below 25 degrees Celsius. Otherwise, needs refrigeration (2-8 degrees Celsius).
• Kit Functionality:
  • Control line indicates if the test is working. If the control line is faint, the kit may be expiring. Check expiry date.
• Procurement:
  • Available directly from Bart Biotic, a Bangalore-based company.
  • Onboarding onto GEM portal is in progress.
• False Positive/Negative Rates:
  • High sensitivity and specificity (around 98%) for both von Willebrand disease and hemophilia A kits.
• Adoption:
  • Union Ministry of Health and Family Welfare will send policy brief with recommendations to all state departments after assessing cost effectiveness.

Manufacturing

• Bart Biotech is the only manufacturer currently.
• Centralized procurement can be facilitated via the GEM portal.

Post POC Test

• Confirmatory gold standard assay is still required for a lifetime report (PT, APTT, factor eight, and factor nine).
• POC test is useful for initial screening, emergencies, and immediate treatment decisions.

Scenario Analysis and Field Testing

• Scenario one tested everyone with the point of care test, while scenario two used initial screening (CBC, PT, APTT) and then the point of care test only for abnormal APTT results.
• Field testing data is limited, but some hospitals have reported positive experiences with outreach activities.

Procurement Support and Contact Information

• NIIH Mumbai team is available to support states in procuring the kit. They were willing to put one lakh or two lakh kits as needed.
• Contact details will be provided in the chat box for Bipin Kulkarni and the NIIH team.

Government Support and Advocacy

• Cost per test details can be used for tender documents.
• Official letter can be issued to state principal secretaries regarding the hemophilia kit.
• Advocacy with Hemophilia Federation of India (HFI) is ongoing.

State Procurement and Program Integration

• Need to include the kit in state procurement portals.
• Provision should be included in state programs like ROP (state program).

Additional Information and Support

• Complete specifications of the kit, including storage details and video demonstrations, will be shared.
• Policy brief will also be shared.

Concluding Remarks and Future Topics

• Next session will be on long-acting reversible contraceptives.
• State governments can suggest topics for future HTA assessments.
• Communication email ID is listed in the chat box for further queries.