TABLE 16.
PIRFENIDONE GRADE EVIDENCE PROFILE*
|
Quality Assessment |
|||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of
Studies |
Design |
Limitations |
Inconsistency |
Indirectness |
Imprecision |
Other
Considerations |
|||||||
| Mortality (follow-up 72 wk) | 4 | Randomized trials | No serious limitations | No serious inconsistency | No serious indirectness‡ | Serious§ | None¶ | ||||||
| Acute Exacerbation (follow-up 72 wk‖) | 4 | Randomized trials | Serious** | No serious inconsistency | No serious indirectness | Serious§ | None¶ | ||||||
| Vital Capacity (follow-up 72 wk; measured with: SMD based on FVC% predicted, VC and FVC; better indicated by higher values) | 4 | Randomized trials | No serious limitations†† | No serious inconsistency | Very serious‡‡ | No serious imprecision | None¶ | ||||||
| Photosensitivity (follow-up 72 wk) | 4 | Randomized trials | No serious limitations | No serious inconsistency | No serious indirectness | No serious imprecision | None¶ | ||||||
| Anorexia | 4 | Randomized trials | No serious limitations | No serious inconsistency | No serious indirectness | No serious imprecision | None¶ | ||||||
| Fatigue | 3 | Randomized trials | No serious limitations | No serious inconsistency | No serious indirectness‖‖ | No serious imprecision | None¶ | ||||||
| Stomach Discomfort | 4 | Randomized trials | No serious limitations | No serious inconsistency | Serious*** | No serious imprecision | None¶ | ||||||
| DlCO (better indicated by lower values) | 4 | Randomized trials | No serious limitations | No serious inconsistency | Serious††† | No serious imprecision*** | None | ||||||
| Oxygen
Saturation (follow-up 9 mo; better indicated by higher
values) |
2 |
Randomized
trials |
No serious
limitations |
No serious
inconsistency |
Serious§§§ |
No serious
imprecision |
None |
||||||
| Summary of
Findings |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| No. of
Patients |
Effect |
|||||||||
| Pirfenidone |
No
Pirfenidone |
Relative(95% CI) |
Absolute |
Quality |
Importance |
|||||
| Mortality (follow-up 72 wk) | 30/526 (5.7%) | 39/486 (8%) | RR, 0.77 (0.49–1.21) | 18 fewer per 1,000 (from 41 fewer to 17 more) | ⊕⊕⊕○ Moderate | Critical | ||||
| Acute Exacerbation (follow-up 72 wk‖) | 10/526 (1.9%) | 14/486 (2.9%) | RR, 0.69 (0.2–2.42) | 9 fewer per 1,000 (from 23 fewer to 41 more) | ⊕⊕○○ Low | Critical | ||||
| Vital Capacity (follow-up 72 wk; measured with: SMD based on FVC% predicted, VC and FVC; better indicated by higher values) | 521 | 485 | — | SMD 0.23 higher (0.06 to 0.41 higher) | ⊕⊕○○ Low | Important§§ | ||||
| Photosensitivity (follow-up 72 wk) | 130/526 (24.7%) | 30/489 (6.1%) | RR, 5.3 (1.46–19.24) ¶¶ | 264 more per 1,000 (from 28 more to 1,119 more) | ⊕⊕⊕⊕ High | Important | ||||
| Anorexia | 78/526 (14.8%) | 18/489 (3.7%) | RR, 3.57 (2.15–5.93) ¶¶ | 95 more per 1,000 (from 42 more to 181 more) | ⊕⊕⊕⊕ High | Important | ||||
| Fatigue | 120/417 (28.8%)¶¶ | 72/382 (18.8%) | RR, 2.54 (0.53–12.18) | 290 more per 1,000 (from 89 fewer to 2,107 more) | ⊕⊕⊕⊕ High | Important | ||||
| Stomach Discomfort | 54/526 (10.3%) | 10/489 (2%) | RR, 4.2 (2.17–8.11) | 65 more per 1,000 (from 24 more to 145 more) | ⊕⊕⊕○ Moderate | Important | ||||
| DlCO (better indicated by lower values) | 526 | 486‡‡‡ | — | Not pooled | ⊕⊕⊕○ Moderate | Important | ||||
| Oxygen
Saturation (follow-up 9 mo; better indicated by higher
values) |
171 |
135 |
— |
MD 0.53 higher
(1.01 lower to 2.06 higher) |
⊕⊕⊕○ Moderate |
Important |
||||
The overall quality of evidence rating is listed in the first row and is the one used in the text of the document. The quality rating for outcomes listed in other rows may differ. How these additional outcomes are rated in terms of quality does not influence the final quality rating as they are to inform, but not to make, decisions.
Importance rating: the relative importance of the outcome for decision making. The rating “critical” indicates making recommendations on choice of testing and treatment strategies. The rating “important” indicates that the outcome is important but not critical for making recommendations.
The studies used slightly different doses of pirfenidone.
There are sparse data, leading to imprecison. The number of events and patients in the studies is too small to show an effect or exclude with confidence that no important effect on mortality is achieved. The confidence intervals are wide.
The number of studies is small and publication bias is difficult to detect given the small number of studies.
Two trials (004 and 006) with follow-up of 72 weeks.
One trial (Azuma and colleagues) stopped early because of perceived benefit in relation to exacerbations.
Data were imputed in studies 004 and 006.
It is not clear how important a change in FVC% is for patients. In one trial vital capacity and not FVC was measured.
The study period data for PFT data were used. The SMD was used because there were no standard deviations given for the absoulte difference in FVC (only for FVC in percent predicted). The FVC data used here are derived from the prespecified imputed data in the FDA document for studies 004 and 006 (Table 8).
Data for 004 and 006 were not provided separately and for the meta-analysis it was assumed that this is one study for this outcome.
It is not clear whether this outcome was continuous and how severe it was (whether it was sporadic or transient).
No explanation was provided.
DlCO is not a patient-important outcome.
It is not clear which patients had DlCO measured and the data provided in the publications do not allow for pooling of the results.
The importance of this outcome measure for patients and the relation to patient-important outcomes is uncertain.