Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is high or moderate to high where GRADE has been performed and there is a trade off between benefits and harms of the intervention.
Population: People with IPF
Intervention: Nintedanib
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality | No statistically significant difference | Moderate |
Disease progression | Favours intervention | Moderate |
Adverse events | Occurs more commonly with nintedanib compared with placebo (favours comparison) | High |
Serious adverse events | No statistically significant difference | Moderate |
Recommendations as stated in the source guideline The guideline committee suggests clinicians use nintedanib in patients with IPF (conditional recommendation, moderate certainty of evidence).
Note The guideline committee noted that their recommendation places a high value on patient-important outcomes such as disease progression and mortality, with a lower value placed on potentially significant adverse events and cost of treatment. There appeared to be some benefit in terms of disease progression but no significant benefit in terms of mortality was observed. The guideline committee also noted that the desirable anticipated effects of nintedanib are probably large.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there is a trade off between benefits and harms of the intervention. ᵃ
Population: People with IPF
Intervention: Pirfenidone
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality | No statistically significant difference | Moderate |
Acute exacerbation | No statistically significant difference | Low |
Oxygen saturation | No statistically significant difference | Low |
Disease progression | Favours intervention | High |
Photosensitivity | Favours comparison | High |
Anorexia | Favours comparison | High |
Fatigue | Favours comparison | Moderate |
Recommendations as stated in the source guideline The guideline committee suggests pirfenidone in patients with IPF (conditional recommendation for moderate confidence in effect estimates).
Note ᵃ The evidence rating is based upon those outcomes listed as critical in the guideline (mortality, acute exacerbation, and disease progression). The other outcomes are listed as important. Whilst there was no statistical difference, the guideline panel felt there were clinically important benefits for the critical outcomes. In making this decision, a high value was put on the potential benefit of pirfenidone on “patient-important outcomes” such as disease progression and mortality, and a lower value on potentially significant adverse effects and the cost of treatment.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: People with IPF
Intervention: Selective endothelin receptor antagonist (ambrisentan)
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality (follow up: median 52 weeks) | No statistically significant difference | Low |
Mortality and/or disease progression: assessed with composite of death and/or disease progression (follow up: median 52 weeks) | Favours comparison | Moderate |
Disease progression: assessed with change in forced vital capacity in % (follow up: median 72 weeks) | No statistically significant difference | Low |
Adverse events (follow up: median 52 weeks) | No statistically significant difference | Moderate |
Serious adverse events (follow up: median 52 weeks) | No statistically significant difference | Low |
Recommendations as stated in the source guideline The guideline committee recommends that clinicians do not use ambrisentan in patients with IPF (strong recommendation; low certainty of the evidence).
Note Based on one study that was stopped early due to a lack of benefit and increased likelihood of mortality in the intervention group. High price of medication would generate an increased use of resources.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: People with IPF
Intervention: Dual endothelin receptor antagonists (bosentan or macitentan)
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality (follow up: 34-86 weeks) | No statistically significant difference | Low |
Mortality or disease progression: assessed with composite of death or disease progression (follow up: 34-86 weeks) | No statistically significant difference | Low |
Disease progression: assessed with change in forced vital capacity in litres (follow up: 52-80 weeks) | No statistically significant difference | Moderate |
Adverse events (follow up: 34-80 weeks) | No statistically significant difference | High |
Serious adverse events (follow up: 34-80 weeks) | No statistically significant difference | High |
Recommendations as stated in the source guideline The guideline committee suggests that clinicians do not use dual endothelin receptor antagonists in patients with IPF (conditional recommendation; low certainty of the evidence).
Note The guideline committee noted large resources required compared with uncertain benefit. Only studies evaluating bosentan or macitentan were included.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: People with IPF
Intervention: Acetylcysteine monotherapy
Comparison: Control
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality (follow up: median 12 months) | No statistically significant difference | Low |
Adverse events (follow up: median 12 months) | No statistically significant difference | Low |
Quality of life: assessed with change in St George's Respiratory Questionnaire (follow up: median 12 months) | No statistically significant difference | Moderate |
Disease progression: assessed with change in FVC in litres (follow up: median 12 months) | No statistically significant difference | High |
Function: assessed with 6-minute walk test in metres (follow up: median 12 months) | Favours intervention | Very Low |
Recommendations as stated in the source guideline The guideline committee suggests that clinicians do not use acetylcysteine monotherapy in patients with IPF (conditional recommendation, low confidence in estimates of effect).
Note Included patients were mild to moderately impaired, so there is uncertainty to what extent the evidence applies to people with severe impairment of pulmonary function.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes. However, this is uncertain and new evidence could change this in the future.
Population: People with IPF
Intervention: Anticoagulants ᵃ
Comparison: No anticoagulants
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality (follow up: 48-52 weeks) | Favours comparison | Low |
Disease progression: assessed with FVC change (L) (follow up: mean 48 weeks) | No statistically significant difference | Low |
Disease progression: assessed with FVC decline ≤10% (follow up: mean 48 weeks) | No statistically significant difference | Low |
Adverse events (follow up: mean 48 weeks) | No statistically significant difference | Low |
Serious adverse events (follow up: mean 48 weeks) | No statistically significant difference | Low |
Recommendations as stated in the source guideline The guideline committee recommends that clinicians do not use warfarin anticoagulation in patients with IPF who do not have a known alternative indication for its use (strong recommendation against, low confidence in effect estimates).
Note Even though the confidence in the evidence as assessed by GRADE was low for all outcomes, the guideline committee felt that the increased risk for mortality required a strong recommendation against using warfarin as a treatment for IPF. However, they clarified that people with IPF with an alternative indication for anticoagulation (e.g., venous thromboembolic disease or atrial fibrillation), should follow the appropriate treatment guidelines for these conditions independent of their underlying IPF. ᵃ The guideline searched for evidence for any anticoagulant therapy but only identified one randomised controlled trial (warfarin versus placebo) that met their inclusion criteria.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: People with IPF
Intervention: Phosphodiesterase-5 inhibitor (sildenafil)
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Mortality (follow up: 6-9 months) | No statistically significant difference | Low |
Exacerbations | No statistically significant difference | Low |
Quality of life: St George Respiratory Questionnaire (SGRQ) | Favours intervention | Moderate |
Disease progression: assessed with Forced Vital Capacity (FVC) in litres | No statistically significant difference | Moderate |
Disease progression: assessed with Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | No statistically significant difference | Low |
Dyspnoea: assessed with a change in Borg Dyspnoea Score | No statistically significant difference | Moderate |
Shortness of Breath Questionnaire (SOBQ) Dyspnoea Score Change | No statistically significant difference | Low |
Oxygen saturation | No statistically significant difference | Low |
Function: measured with change in 6-minute walk distance | No statistically significant difference | Low |
Recommendations as stated in the source guideline The guideline committee suggests that clinicians not use sildenafil, a phosphodiesterase-5 inhibitor, for treatment of IPF (conditional recommendation against, moderate confidence in estimates of effect).
Note Despite the small improvement in quality of life with sildenafil there was felt to be net harm due to the lack of benefit for any other outcome.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes. However, this is uncertain and new evidence could change this in the future.
Population: Adults with chronic lung disease (ILD or COPD) ᵃ who have severe chronic resting room air hypoxaemia
Intervention: Long-term oxygen therapy (LTOT)
Comparison: No LTOT
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
LTOT (not further defined) versus room air in people with ILD | ||
Mortality at 12, 24, and 36 months ᵇ | No statistically significant difference | Very Low |
LTOT prescribed for at least 15 hours/day versus no LTOT in people with COPD | ||
5-year mortality risk | Favours intervention | Moderate |
Hospitalisations over 3 years | Favours intervention | Low |
Recommendations as stated in the source guideline The guideline panel recommends that for adults with ILD who have severe chronic resting room air hypoxaemia, LTOT is prescribed for at least 15 hours per day (strong recommendation, very low-quality evidence).
Note The overall evidence rating for this table reflects that the evidence for effectiveness comes from an indirect population of people with COPD. Included in this table is randomised controlled trial (RCT) evidence comparing LTOT with no LTOT. For people with COPD, the guideline also included two non-randomised studies and one RCT that compared LTOT prescribed for 24 hours a day with nocturnal LTOT. See guideline for more details. ᵃ The guideline panel noted that there were no published studies that met their inclusion criteria for people with ILD. They found one unpublished RCT (62 people; 49 with idiopathic pulmonary fibrosis) which did report on outcomes of interest. Due to the lack of published evidence answering this question, the guideline panel chose to consider indirect evidence from trials of people with COPD, along with their clinical experience, other published guidelines and ethical issues around withholding LTOT, when making the above recommendation for people with ILD. Please see the guideline for more details. ᵇ Defined as a critical outcome by the guideline panel; no evidence was found for the important outcomes of dyspnoea, fatigue, health-related quality of life, physical activity in daily life, healthcare resource use, exercise capacity, and safety.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes. However this is uncertain and new evidence could change this in the future.
Population: People with IPF
Intervention: Proton-pump inhibitor or H2 antagonist
Comparison: No proton-pump inhibitor or H2 antagonist (no additional information)
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Disease progression at 1 year: measured as ≥10% decline in forced vital capacity (FVC) ≥50 m decline in 6-minute walk distance (6MWD), or death | No statistically significant difference | Very Low |
Disease progression at 1 year: measured as ≥10% or ≥5% decline in FVC or death | Favours intervention | Very Low |
Overall mortality 1 to 5 years ᵃ | No statistically significant difference | Very Low |
IPF-related mortality: 1 to 2.6 years | No statistically significant difference | Very Low |
Exacerbations: 30 weeks to 1 year | No statistically significant difference | Very Low |
Hospitalisations: at 90 days or at 30 weeks to 1 year, or at 1 year to 2.4 years | No statistically significant difference | Very Low |
Lung function ᵇ | No statistically significant difference | Very Low |
Lung function at 90 days (L) and at 90 days (% predicted): measured as FVC | Favours intervention | Very Low |
Respiratory symptoms ᶜ | No statistically significant difference | Very Low |
All adverse effects at 1 year ᵈ | No statistically significant difference | Very Low |
Recommendations as stated in the source guideline We suggest not treating patients with IPF with antacid medication for the purpose of improving respiratory outcomes (conditional recommendation, very low quality evidence).
Note ᵃ The guideline also reported results for overall mortality at 90 days, 30 weeks, 1 year and 5 years. All time points reported no statistically significant difference between treatment groups underpinned by very low quality evidence. ᵇ Lung function was measured at 90 days (mmol/min/kPa - measured as diffusion capacity for carbon monoxide [DLCO]); 90 days (% predicted - DLCO); 90 days ([m] - measured as 6MWD); 30 weeks ([m] - 6MWD); 30 weeks ([L] - measured as change in FVC); 1 year ([L] - FVC); 1 year (% predicted) - FVC); 1 year ([m] - 6MWD). ᶜ Respiratory symptoms were measured at 90 days (Leicester Cough Questionnaire Score); 90 days (cough/day - 24 hour cough frequency); 8 weeks (cough/day - 24 hour cough frequency); 30 weeks (University of California San Diego Shortness of Breath Questionnaire); 30 weeks (change in the St. George’s Respiratory Questionnaire score). All time points reported no statistically significant difference between treatment groups underpinned by very low quality evidence. ᵈ The guideline committee also reported results for all adverse effects at 90 days; Severe adverse effects at 90 days; Gastrointestinal adverse effects at 90 days and 1 year; Pulmonary infection adverse effects at 90 days and 1 year. All of which found no statistically significant difference between treatment groups, underpinned by very low quality evidence. Severe adverse effects at 1 year occurred more commonly with proton pump inhibitors or H2 antagonists compared with no proton pump inhibitors or H2 antagonists, also underpinned by very low quality evidence.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes. However, this is uncertain and new evidence could change this in the future.
Population: People (mean age 50-76 years) with refractory breathlessness associated with chronic obstructive pulmonary disease
Intervention: Opioids
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Breathlessness: change from baseline | No statistically significant difference ᵃ | Very Low |
Breathlessness: post-treatment score | Favours intervention | Low |
Exercise tolerance: 6‐minute walk test: total distance ᵇ | No statistically significant difference ᶜ | Very Low |
Exercise tolerance: 6‐minute walk test: change from baseline ᵇ | Favours comparison | Very Low |
Quality of life | No statistically significant difference | Very Low |
Adverse events: constipation | Occurs more commonly with opioids compared with placebo (favours comparison) | Very Low |
Adverse events: nausea and vomiting | Occurs more commonly with opioids compared with placebo (favours comparison) | Very Low |
Adverse events: drowsiness | Occurs more commonly with opioids compared with placebo (favours comparison) | Very Low |
Note The overall rating in this table reflects the only primary outcome of breathlessness as defined by the Cochrane review which underpins this Cochrane Clinical Answer (CCA). The other outcomes in this table have been classed as secondary outcomes by the Cochrane review. The Cochrane review underlying this CCA noted that this evidence applies to oral or parenteral opioids. They found no evidence for nebulised opioids. ᵃ Although the difference was not statistically significant, the standardised mean change from baseline was 0.11 points better with opioids compared with placebo (ranging from a 0.40 point reduction in breathlessness to a 0.19 point increase). ᵇ Based on a subgroup analysis. The CCA also reports other subgroup analyses for exercise tolerance with a statistically significant difference in favour of opioids for exercise tolerance (workload watts and maximum work cycle) and no statistically significant difference between treatment groups for exercise tolerance (treadmill distance and time on treadmill). A GRADE assessment was not performed for these subgroups. See the CCA for more details. ᶜ Although the difference was not statistically significant, the total distance was 28 metres better with opioids compared with placebo (ranging from 113 metres better to 58 metres worse).
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
- How do opioids compare with placebo for reducing refractory breathlessness in adults with advanced disease and terminal illness?
Use of this content is subject to our disclaimer