Salmeterol compared with slow‐release terbutaline in nocturnal asthma A multicenter, randomized, double‐blind, double‐dummy, sequential clinical trial

Brambilla, Christian; Chastang, Claude; Georges, D; Bertin, L.

doi:10.1111/j.1398-9995.1994.tb00834.x

Cited by 39 publications

(6 citation statements)

References 25 publications

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“…All these approaches allow the use of sequential methods in the design and analysis of trials in which the primary clinical concern is the trade-off between the chance of improved efficacy and toxicity (as encountered in trials of aggressive treatments for fatal disease). Even though sequential methods are used more and more in various therapeutic areas [29][30][31][32][33], selection of the proper statistical design (whether SSD or sequen-tial) always depends on the type of clinical study about to be conducted, and there are many clinical trials for which the SSD remains most appropriate (for instance, trials in which the endpoint is obtained very slowly compared with the recruitment rate).…”

Section: Discussionmentioning

confidence: 99%

Comparison of four sequential methods allowing for early stopping of comparative clinical trials

Sebille¹

2000

Clinical Science

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Phase III trials aim to assess whether a new treatment has superior efficacy than a standard treatment. Sequential methods, such as the sequential probability ratio test (SPRT), the triangular test (TT) and so-called one-parameter boundaries (OPB), now allow early stopping of such trials, both in the case of efficacy (alternative hypothesis; H(1)) and in the case of lack of efficacy (null hypothesis; H(0)). We compared the statistical properties of the SPRT and the TT, and of OPB with Pocock (OPB(Delta=0.5)) and O'Brien and Fleming (OPB(Delta=0)) type boundaries, in the setting of one-sided comparative trials with normal response. We studied the type I error (alpha), power (1-beta), average sample number (ASN) and 90th percentile (P90) of the number of patients required to reach a conclusion using simulations. The four tests were also compared with the corresponding single-stage design (SSD). All sequential tests display alpha and 1-beta close to nominal values and, as compared with SSD, allow important decreases in ASN: for example, -48%, -42%, -40% and -31% under H(0) and H(1) for SPRT, TT, OPB(Delta=0.5) and OPB(Delta=0) respectively. For situations between H(0) and H(1), ASNs of all sequential tests were still smaller than the sample size required by SSD, with the TT displaying the largest decrease (-25%). The P90s of the TT and OPB(Delta=0) under H(0) and H(1) were smaller than the P90s of the SPRT and OPB(Delta=0.5), which were similar to the sample size required by SSD. If all sequential tests display approximately similar features, the TT is the most appealing regarding decreases in sample size, especially for situations between H(0) and H(1).

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Section: Discussionmentioning

confidence: 99%

Comparison of four sequential methods allowing for early stopping of comparative clinical trials

Sebille¹

2000

Clinical Science

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“…The extent of the influence of a wrong estimation of the response rate π 0 under standard treatment was investigated on the statistical properties of the one‐ and two‐sided SSDs, STT, and DTT and all tests were compared by simulation. This topic is indeed important to consider as sequential tests have been more and more used in various therapeutic areas [9–19].…”

Section: Discussionmentioning

confidence: 99%

“…The extent of the influence of a wrong estimation of the response rate p 0 under standard treatment was investigated on the statistical properties of the one-and twosided SSDs, STT, and DTT and all tests were compared by simulation. This topic is indeed important to consider as sequential tests have been more and more used in various therapeutic areas [9][10][11][12][13][14][15][16][17][18][19]. The well-known statistical properties of the STT and DTT were found when p 0 was correctly estimated: type I and II errors accurately maintained and substantial sample size reduction as compared with the corresponding SSDs.…”

Section: Discussionmentioning

confidence: 99%

Impact of a misspecification of the response rate under standard treatment in sequential clinical trials

Sébille

2005

Fundamemntal Clinical Pharma

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Phase III trials are aimed at assessing whether new treatments have superior efficacy than standards. Sequential methods, such as the single triangular test (STT) and the double triangular test (DTT), allow for early stopping of such trials. They use stopping boundaries which depend, for a binary endpoint, on pi(0) and pi(1) (response rates under standard and new treatment, respectively) and alpha and beta (type I and II errors, respectively). Thus, a wrong estimation of pi(0) at planning phase might have an influence on their statistical properties. We assessed the extent of this influence by simulations regarding alpha, 1--beta, and average sample number (ASN) and compared the two methods with the one-sided and two-sided single-stage designs (SSD). There was no influence on alpha for any test and the power achieved by the one-sided or two-sided SSD was moderately affected by a wrong estimation of pi(0). However, important drifts (whose magnitude depended on chosen design) were observed for sequential methods concerning power and ASN in case of moderate under- or overestimation of pi(0) (+/-20% compared with its 'true' value). For example, when 'true' values of pi(0) and pi(1) are 0.30 and 0.40, respectively, using design values of 0.10 and 0.20, the power is 0.57 and 0.50 for the STT and DTT, respectively, instead of 0.95. When 'true' values of pi(0) and pi(1) are 0.10 and 0.20, respectively, using design values of 0.30 and 0.40, the ASN under H(0) is 1,309 and 2,019 for the STT and DTT, respectively, instead of 392 and 601, respectively, using the right design. Using sequential methods in comparative clinical trials with binary responses requires a precise knowledge of the response rate under standard treatment to avoid losses in power or inappropriate increases in sample size.

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“…Não observamos maior incidência de efeitos colaterais em todos os grupos avaliados. A maioria dos estudos multicêntricos realizados envolvem pacientes adolescentes e adultos e todos são unâ-nimes em apontar melhor controle da asma após a introdução do salmeterol em uso de modo regular 1,4,5,[29][30][31] . Revelados por decréscimo nos escores clínicos, melhora das provas de função pulmonar, maior estabilidade do pico do fluxo expiratório, menor consumo de b2 agonistas de curta duração, menor freqüência de distúrbios de sono, entre tantos outros.…”

Section: Discussionunclassified

Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered dose inhaler) in children with acute asthma attack

Solé¹,

Rizzo²,

Porto³

et al. 1996

J Pediatr (Rio J)

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Patients during a mild to moderate acute attack of asthma (FEV1: 50 -80% of predicted) were treated with Salmeterol MDI -50mcg or Rotadisk -50mcg or Salbutamol (MDI200mcg). The children were followed by Spirometry, measuring FEV1 (basal) and after treatment: at 30 minutes, 60 minutes and thereafter every 60 minutes until 780 minutes, if the patients mantained the FEV1 above 80% of the predicted value and/or an increment of 20% in the VEF1 basal value. The Salmeterol group showed a significant bronchodilation at 60 minutes which was maintained in half of the patients up to 9 hours. This was not observed in the Salbutamol group: the peak bronchodilatation was observed at 30 minutes and the bronchodilation effect was observed in half of the patients up to 6 hours. There were no significant differences between both presentations of Salmeterol. This drug allowed a prolonged bronchodilator effect and is, according to the several consensus on management of asthma, an adequate option in the treatment of moderate to severe asthma.

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Salmeterol compared with slow‐release terbutaline in nocturnal asthma A multicenter, randomized, double‐blind, double‐dummy, sequential clinical trial

Cited by 39 publications

References 25 publications

Comparison of four sequential methods allowing for early stopping of comparative clinical trials

Comparison of four sequential methods allowing for early stopping of comparative clinical trials

Impact of a misspecification of the response rate under standard treatment in sequential clinical trials

Duration of bronchodilator effect of inhaled Salmeterol (dry powder x metered dose inhaler) in children with acute asthma attack

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