Spanish HTA of transbronchial lung biopsy using cryoprobes (cryobiopsy) in diffused lung diseases

The use of cryoprobes in transbronchial lung biopsy (TBLB) has dramatically improved the diagnostic yield of this procedure and obtains larger, higher quality tissue samples than the use of conventional methods. This technique may modify the diagnostic algorithm and may benefit many patients as a possible alternative to surgical lung biopsy (SLB).

REDETS wanted to assess the scientific evidence of the diagnostic yield, safety and cost-effectiveness of cryobiopsy in the diagnosis of diffuse interstitial lung diseases (DILD) compared with SLB and traditional TBLB. “Diagnostic yield” is defined as the percentage of patients in whom a sample can be obtained and used to diagnose correctly.

REDETS has performed a Systematic review of clinical guidelines, health technology assessment reports, systematic reviews and original articles describing the usefulness of cryobiopsy in the diagnosis of DILD. A comprehensive literature search (until June 2016) of clinical guidelines repositories and HTA reports (NICE Evidence Search and the AHRQ Guidelines Clearinghouse) and the MEDLINE, EMBASE and Cochrane Library bibliographic databases was performed. Evaluation of the methodological quality of the documents selected was evaluated using AMSTAR for systematic reviews and an adaptation of the QUADAS-2 questionnaire for original studies

REDETS identified one (1) systematic review and three (3) studies were considered for the analysis. All three studies and the systematic reviews provide the same conclusions. Diagnostic yield for cryobiopsy is 76.9% (95% CI: 67.2-85.3) to 85.9% (95% CI: 78.2-92.2) depending on whether the diagnosis was considered definitive or probably definitive. Comparing cryobiopsy with a surgical lung biopsy, the diagnostic yield of the first compared with surgical biopsy guided by video-assisted thoracoscopic surgery (VATS) shows the yield of cryobiopsy to be lower (83% [95% CI: 78% -87%] vs. 99% [95% CI: 95% -100%]). VATS mortality is higher (2.7% vs. 0.3%, p = 0.045), as is the number of exacerbations (3.3% vs. 0.3%). The mean time to the first adverse event after surgical biopsy was 27.5 ± 73.9 days, versus 0.6 ± 2 days after cryobiopsy. The number of days of hospitalization was significantly shorter for cryobiopsy (2.6 days [0-17] vs. 6.1 days [3-48]). The rate of patients needing an SLB to confirm the diagnosis after a cryobiopsy ranged from 3.6% to 28%. A cost study included in the systematic review mentioned above concluded that cryobiopsy could save between 953 and 1925 euros per patient compared to SLB. Comparing cryobiopsy with conventional transbronchial lung biopsy, cryobiopsy holds a significantly higher diagnostic yield compared to traditional TBLB (86.3% [95% CI: 80.2%-90.8%] vs. 56.5% [95% CI: 27.5%-83.2%]), as well as an odds ratio for reaching a diagnosis of 6.7 (95% CI: 3.6-12.4). The size of the tissue sample obtained with the cryobiopsy procedure was significantly larger than with conventional TBLB (20.4 vs. 4.3 mm2, p = 0.005).

To sum up:

• The diagnostic yield of surgical lung biopsy by VATS is superior to that of cryobiopsy, but this comes at the cost of increased mortality and an increase in the number of exacerbations of the disease
• The diagnostic yield of cryobiopsy is superior to that of conventional transbronchial lung biopsy; the procedure obtains larger and higher quality tissue samples
• Cryobiopsy is a safe test that is associated with few complications or adverse effects. These safety results are limited to the populations included in the studies, and may not be representative of the test’s safety in patients with higher morbidity and mortality due to reduced lung function, hemodynamic instability or other factors
• Initial use of cryobiopsy might avoid the need to perform surgical biopsies in a significant number of patients. However, multicentre clinical trials are necessary to confirm these results in different scenarios and in the various entities that comprise diffuse interstitial lung disease
• The use of cryobiopsy is expected to reduce the costs associated with a surgical lung biopsy. However, further studies are necessary to evaluate its possible cost-effectiveness or cost-utility in more detail

See the full report in Spanish (with summary in English) here.

Subscribe to our newsletter delivered every second week not to miss important reimbursement information.