Skewed analysis

Abstract

While Cahill et al1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar are to be credited for considerable work addressing an important problem in their decision and economic analysis, the numbers don't add up, and the conclusion is unsubstantiated.Table 1 proposes the probability of the cervix measurement ≤15 mm is 0.0119 (0.0100-0.0168).1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Based upon the model hypothetical cohort population of 4 million, the number of women with cervix measurement ≤15 mm would be 47,600. If 100% of these women received progestogen, then based upon the chosen reference study2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar (relative risk, 0.56; 95% confidence interval, [CI], 0.36–0.862Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar), 7235 preterm births (PTB) would be prevented, with a 95% CI of 2292–10,479–not the 95,920 proposed in Table 4.1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The overestimate of PTB prevention by a factor of 13 skews the model in favor of universal sonographic screening and produces a total cost saved >13 times the reasonable optimal scenario. Furthermore, assuming that 100% of women would be screened and that 100% of women with a cervix ≤15 mm would receive progestogen would be unreasonable in a real-world effectiveness model. The CI demonstrates that, even under the optimized model, as few as 2292 PTB might be prevented.The purpose of modeling cervical length screening combined with progestogen treatment for short cervix would be a reasonable belief that treating pregnant women with short cervix ≤15 mm with progestogen would decrease PTB–this is based upon 67 total events from 1 study.2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google ScholarThe authors chose not to include the study of O'Brien et al3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar in Table 1,1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar despite the fact that it is the largest single trial of progestogens to prevent PTB and has a risk of bias equivalent or superior to the studies of Meis et al4Meis P.J. Klebanoff M. Thom E. et al.Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.N Engl J Med. 2003; 348: 2379-2385Crossref PubMed Scopus (1256) Google Scholar or Fonseca et al.2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar The authors infer that they excluded the study of O'Brien et al3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar on the basis that the progestogen formulation was different; yet O'Brien et al3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar used vaginal progesterone and the model of Cahill et al1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar used vaginal progestogen.Finally, the cost-effectiveness model is heavily influenced by cost of neonatal severe morbidity, which is estimated to be >19,000 times more expensive than the advocated test (ultrasound), and advocated intervention (progestogen). Therefore, it is important to get numbers right, since slight changes in the number of severe morbidity cases would swing the cost dramatically. The trials used to support the intervention of progestogen to prevent PTB2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar, 3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar do not provide evidence of reduction in neonatal severe morbidity; therefore the model layers presumption based upon inference and the gestalt conclusion is unsupportable. While Cahill et al1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar are to be credited for considerable work addressing an important problem in their decision and economic analysis, the numbers don't add up, and the conclusion is unsubstantiated. Table 1 proposes the probability of the cervix measurement ≤15 mm is 0.0119 (0.0100-0.0168).1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Based upon the model hypothetical cohort population of 4 million, the number of women with cervix measurement ≤15 mm would be 47,600. If 100% of these women received progestogen, then based upon the chosen reference study2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar (relative risk, 0.56; 95% confidence interval, [CI], 0.36–0.862Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar), 7235 preterm births (PTB) would be prevented, with a 95% CI of 2292–10,479–not the 95,920 proposed in Table 4.1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The overestimate of PTB prevention by a factor of 13 skews the model in favor of universal sonographic screening and produces a total cost saved >13 times the reasonable optimal scenario. Furthermore, assuming that 100% of women would be screened and that 100% of women with a cervix ≤15 mm would receive progestogen would be unreasonable in a real-world effectiveness model. The CI demonstrates that, even under the optimized model, as few as 2292 PTB might be prevented. The purpose of modeling cervical length screening combined with progestogen treatment for short cervix would be a reasonable belief that treating pregnant women with short cervix ≤15 mm with progestogen would decrease PTB–this is based upon 67 total events from 1 study.2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar The authors chose not to include the study of O'Brien et al3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar in Table 1,1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar despite the fact that it is the largest single trial of progestogens to prevent PTB and has a risk of bias equivalent or superior to the studies of Meis et al4Meis P.J. Klebanoff M. Thom E. et al.Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.N Engl J Med. 2003; 348: 2379-2385Crossref PubMed Scopus (1256) Google Scholar or Fonseca et al.2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar The authors infer that they excluded the study of O'Brien et al3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar on the basis that the progestogen formulation was different; yet O'Brien et al3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar used vaginal progesterone and the model of Cahill et al1Cahill A.G. Odibo A.O. Caughey A.B. et al.Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.Am J Obstet Gynecol. 2010; 202 (e1-8): 548Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar used vaginal progestogen. Finally, the cost-effectiveness model is heavily influenced by cost of neonatal severe morbidity, which is estimated to be >19,000 times more expensive than the advocated test (ultrasound), and advocated intervention (progestogen). Therefore, it is important to get numbers right, since slight changes in the number of severe morbidity cases would swing the cost dramatically. The trials used to support the intervention of progestogen to prevent PTB2Fonseca E.B. Celik E. Parra M. Singh M. Nicolaides K.H. Progesterone and the risk of preterm birth among women with a short cervix.N Engl J Med. 2007; 357: 462-469Crossref PubMed Scopus (810) Google Scholar, 3O'Brien J.M. Adair C.D. Lewis D.F. et al.Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.Ultrasound Obstet Gynecol. 2007; 30: 687-696Crossref PubMed Scopus (226) Google Scholar do not provide evidence of reduction in neonatal severe morbidity; therefore the model layers presumption based upon inference and the gestalt conclusion is unsupportable. Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysisAmerican Journal of Obstetrics & GynecologyVol. 202Issue 6PreviewThe purpose of this study was to estimate which strategy is the most cost-effective for the prevention of preterm birth and associated morbidity. Full-Text PDF ReplyAmerican Journal of Obstetrics & GynecologyVol. 204Issue 5PreviewWe appreciate the recent interest by Dr Andrews in our study entitled, “Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis,” as well as the opportunity to clarify a few points raised in his letter. Full-Text PDF