On 2017 Sep 25, Peter Gøtzsche commented:

The primary outcome in the trial called TORCH (“Towards a Revolution in COPD Health”) was total mortality. GlaxoSmithKline randomised 6184 patients to four groups: placebo; salmeterol; fluticasone; and both drugs together. This factorial design is powerful, as it allows the investigators to study three research questions with a sample size that would usually only allow one question to be answered. Such a trial can tell us whether the two drugs are effective, and whether the combination is better than any of its components.

However, nowhere in the 15-page trial report is the factorial analysis to be found, and the abstract gives the readers the impression that the combination was better than any of its components. The analysis in the TORCH trial included only half of the patients, thereby spoiling the advantage of the factorial design, although the published trial protocol stated that a factorial analysis was to be performed (1).

The authors of a letter to the editor used a factorial analysis and showed that the effect of the combination was entirely due to salmeterol (2); the hazard ratio for fluticasone was 1.00 (0.87 to 1.15), p = 0.99. In other similar trials, both GlaxoSmithKline and AstraZeneca did not perform a factorial analysis (3).

1 Gøtzsche PC. Questionable research and marketing of a combination drug for smoker’s lungs. J R Soc Med 2014;107:256-7.

2 La Vecchia C and Fabbri LM. Prevention of death in COPD. N Engl J Med 2007;356:2211–2.

3 Suissa S, Ernst P, Vandemheen KL, et al. Methodological issues in therapeutic trials of COPD. Eur Respir J 2008;31:927–33.

On 2017 Sep 07, Peter Gøtzsche commented:

The primary outcome in the trial called TORCH (“Towards a Revolution in COPD Health”) was total mortality, which was not analysed correctly. GlaxoSmithKline randomised 6184 patients to four groups: placebo; salmeterol; fluticasone; and both drugs together. This factorial design is powerful, as it allows the investigators to study three research questions with a sample size that would usually only allow one question to be answered. Such a trial can tell us whether the two drugs are effective, and whether the combination is better than any of its components.

However, in violation with the published trial protocol (1), nowhere in the 15-page trial report is the correct factorial analysis to be found, and the abstract gives the readers the clear impression that the combination was better than any of its components. The misleading analysis in the TORCH trial included only half of the patients, thereby spoiling the advantage of the factorial design.

The authors of a letter to the editor showed the correct factorial analysis. The effect of the combination was entirely due to salmeterol (2). In contrast, the hazard ratio for fluticasone was 1.00 (0.87 to 1.15), p = 0.99. There was no good reason why a factorial analysis was not done and published (1). Both GlaxoSmithKline and AstraZeneca have not performed the appropriate analysis in other similar trials as well (3).

1 Gøtzsche PC. Questionable research and marketing of a combination drug for smoker’s lungs. J R Soc Med 2014;107:256-7.

2 La Vecchia C and Fabbri LM. Prevention of death in COPD. N Engl J Med 2007;356:2211–2.

3 Suissa S, Ernst P, Vandemheen KL, et al. Methodological issues in therapeutic trials of COPD. Eur Respir J 2008;31:927–33.

On 2017 Aug 28, Peter Gøtzsche commented:

None

On 2017 Aug 28, Peter Gøtzsche commented:

None

On 2017 Sep 07, Peter Gøtzsche commented:

The primary outcome in the trial called TORCH (“Towards a Revolution in COPD Health”) was total mortality, which was not analysed correctly. GlaxoSmithKline randomised 6184 patients to four groups: placebo; salmeterol; fluticasone; and both drugs together. This factorial design is powerful, as it allows the investigators to study three research questions with a sample size that would usually only allow one question to be answered. Such a trial can tell us whether the two drugs are effective, and whether the combination is better than any of its components.

However, in violation with the published trial protocol (1), nowhere in the 15-page trial report is the correct factorial analysis to be found, and the abstract gives the readers the clear impression that the combination was better than any of its components. The misleading analysis in the TORCH trial included only half of the patients, thereby spoiling the advantage of the factorial design.

The authors of a letter to the editor showed the correct factorial analysis. The effect of the combination was entirely due to salmeterol (2). In contrast, the hazard ratio for fluticasone was 1.00 (0.87 to 1.15), p = 0.99. There was no good reason why a factorial analysis was not done and published (1). Both GlaxoSmithKline and AstraZeneca have not performed the appropriate analysis in other similar trials as well (3).

1 Gøtzsche PC. Questionable research and marketing of a combination drug for smoker’s lungs. J R Soc Med 2014;107:256-7.

2 La Vecchia C and Fabbri LM. Prevention of death in COPD. N Engl J Med 2007;356:2211–2.

3 Suissa S, Ernst P, Vandemheen KL, et al. Methodological issues in therapeutic trials of COPD. Eur Respir J 2008;31:927–33.

On 2017 Sep 25, Peter Gøtzsche commented:

The primary outcome in the trial called TORCH (“Towards a Revolution in COPD Health”) was total mortality. GlaxoSmithKline randomised 6184 patients to four groups: placebo; salmeterol; fluticasone; and both drugs together. This factorial design is powerful, as it allows the investigators to study three research questions with a sample size that would usually only allow one question to be answered. Such a trial can tell us whether the two drugs are effective, and whether the combination is better than any of its components.

However, nowhere in the 15-page trial report is the factorial analysis to be found, and the abstract gives the readers the impression that the combination was better than any of its components. The analysis in the TORCH trial included only half of the patients, thereby spoiling the advantage of the factorial design, although the published trial protocol stated that a factorial analysis was to be performed (1).

The authors of a letter to the editor used a factorial analysis and showed that the effect of the combination was entirely due to salmeterol (2); the hazard ratio for fluticasone was 1.00 (0.87 to 1.15), p = 0.99. In other similar trials, both GlaxoSmithKline and AstraZeneca did not perform a factorial analysis (3).

1 Gøtzsche PC. Questionable research and marketing of a combination drug for smoker’s lungs. J R Soc Med 2014;107:256-7.

2 La Vecchia C and Fabbri LM. Prevention of death in COPD. N Engl J Med 2007;356:2211–2.

3 Suissa S, Ernst P, Vandemheen KL, et al. Methodological issues in therapeutic trials of COPD. Eur Respir J 2008;31:927–33.