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Time to full publication of studies of anticancer drugs for breast cancer, and the potential for publication bias

Published online by Cambridge University Press:  08 January 2010

Petra Harris ,
Andrea Takeda ,
Emma Loveman  and
Debbie Hartwell
Petra Harris
Affiliation:
Southampton Health Technology Assessments Centre
Andrea Takeda
Affiliation:
Southampton Health Technology Assessments Centre
Emma Loveman
Affiliation:
Southampton Health Technology Assessments Centre
Debbie Hartwell
Affiliation:
Southampton Health Technology Assessments Centre
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Abstract

Objectives: Nonpublication of results of clinical trials can contribute to inappropriate medical decisions. The primary aim of this systematic review was to investigate publication delays between conference abstracts and full journal publications from randomized controlled trial results of new anticancer agents for breast cancer. The review was restricted to anticancer agents previously, or due to be, appraised in the United Kingdom by the National Institute for Health and Clinical Excellence. A secondary objective was to identify whether there are any apparent biases in the publication and reporting of these trials.

Methods: We searched six electronic databases up to August 2007, including Medline and the Cochrane Library. Two reviewers independently selected studies, extracted and assessed the data.

Results: Six anticancer treatments were identified: docetaxel, paclitaxel, trastuzumab, gemcitabine, lapatinib, and bevacizumab. Of eighteen included trials, only four publications from three trials reported the same outcomes in both abstract and full publication. Time delays ranged from 5 to 19 months. Eleven trial abstracts were still without a full publication at the end of our searches, varying from 3 to 38 months since abstract publication. Observational analysis revealed no particular publishing biases.

Conclusions: Whereas delays in publication appear reasonable over a period of months, many were not published in full over a period of years and others would appear to be unlikely to ever be published. Further research should investigate the impact of publication delays on the availability of new drug treatments in clinical practice.

Keywords

Breast cancer drugsMethodologyPublication delaySystematic review
Type
METHODS
Information
International Journal of Technology Assessment in Health Care , Volume 26 , Issue 1 , January 2010 , pp. 110 - 116
Copyright
Copyright © Cambridge University Press 2010

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References

REFERENCES

1. Al-Marzouki, S, Roberts, I, Marshall, T, et al. The effect of scientific misconduct on the results of clinical trials: A Delphi survey. Contemp Clin Trials. 2005;26:331–337.CrossRefGoogle ScholarPubMed
2. Albain, KS, Nag, S, Calderillo-Ruiz, G, et al. Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall survival. J Clin Oncol. 2004;22 (Suppl):A510.CrossRefGoogle Scholar
3. Blohmer, J, Kaufman, M, Eiermann, W et al. , First analysis of the event-free survival of the GeparDuo-study: Neoadjuvant doxorubicin / cyclophosphamide followed by docetaxel (AC-Doc) versus dose-dense doxorubicin and docetaxel (ADoc) in breast cancer. Abstract from 27 Deutscher Krebskongress Berlin. 2006.Google Scholar
4. Burstein, HJ, Spigel, D, Kindsvogel, K, et al. Metronomic chemotherapy with and without bevacizumab for advanced breast cancer: A randomized phase II study. Breast Cancer Res Treat. 2005;94:S6.Google Scholar
5. Cameron, D, Stein, S, Zaks, T et al. , Lapatinib plus capecitabine shows superior efficacy compared to capecitabine alone in patients with ErbB2 positive advanced or metastatic breast cancer initial biomarker data. Proceedings from the 2006 annual San Antonio Breast Cancer Symposium, December 15, 2006. (Abstract 2).Google Scholar
6. Carmichael, J. Current issues in cancer: Cancer chemotherapy: Identifying novel anticancer drugs. BMJ. 1994;308:1288–1290.CrossRefGoogle Scholar
7. Centre for Reviews and Dissemination (CRD). Undertaking systematic reviews of research on effectiveness. Report No. 4. York: CRD; 2001.Google Scholar
8. Chalmers, I. Underreporting research is scientific misconduct. JAMA. 1990;263:1405–1408.CrossRefGoogle ScholarPubMed
9. Dickersin, K, Olson, CM, Rennie, D, et al. Association between time interval to publication and statistical significance. JAMA. 2002;287:2829–2831.CrossRefGoogle ScholarPubMed
10. Geyer, CE, Forster, J, Lindquist, D, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–2743.CrossRefGoogle ScholarPubMed
11. Geyer, CE, Martin, A, Newstat, B, et al. Lapatinib (L) plus capecitabine (C) in HER2+ advanced breast cancer (ABC): Genomic and updated efficacy data. J Clin Oncol. 2007;25 (Suppl):A1035.CrossRefGoogle Scholar
12. Henderson, IC, Berry, D. Demetri GD. Improved disease free and overall survival from the addition of sequential paclitaxel but not from the escalation of doxorubicin dose level in the adjuvant chemotherapy of patients with node-positive primary breast cancer (abstract). Proc Am Soc Clin Oncol. 1998;17:A390.Google Scholar
13. Henderson, I, Berry, D, Demetri, G, et al. Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node positive primary breast cancer. J Clin Oncol. 2003;21:976–983.CrossRefGoogle ScholarPubMed
14. Jackisch, C, von Minckwitz, G, Eidtmann, H, et al. Dose-dense biweekly doxorubicin/docetaxel versus sequential neoadjuvant chemotherapy with doxorubicin/cyclophosphamide/docetaxel in operable breast cancer: Second interim analysis. Clin Breast Cancer. 2002;3:276–280.CrossRefGoogle ScholarPubMed
15. Krzyzanowska, M, Pintilie, M. Tannock I. Factors associated with failure to publish large randomized trials presented at an oncology meeting. JAMA. 2003;290:495–501.CrossRefGoogle ScholarPubMed
16. Lyons, JA, Silverman, P, Remick, S, et al. Toxicity results and early outcome data on a randomized phase II study of docetaxel +/− bevacizumab for locally advanced, unresectable breast cancer. J Clin Oncol. 2006;24:133S.CrossRefGoogle Scholar
17. Mamounas, EP. Evaluating the use of paclitaxel following doxorubicin/ cyclophosphamide in patients with breast cancer and positive axillary node (abstract). Proceedings from the NIH Consensus Development Conference on Adjuvant Therapy for Breast Cancer; November 1–3, 2000, Bethesda, MD.Google Scholar
18. Mamounas, EP, Bryant, J, Lembersky, BC, et al. Paclitaxel (T) following doxorubicin/cyclophosphamide (AC) as adjuvant chemotherapy for node-positive breast cancer: Results from NSABP B-28. Proc Am Soc Clin Oncol. 2003;22:A12.Google Scholar
19. Martin, M, Pienkowski, T, Mackey, J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352:2302–2313.CrossRefGoogle ScholarPubMed
20. McIntyre, J, Moral, M, Bozzo, J. Combination therapy with valproic acid in cancer: Initial clinical approach. Drugs Fut. 2007;32:45–50.CrossRefGoogle Scholar
21. Miller, KD, Wang, M, Gralow, J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: A trial coordinated by the Eastern Cooperative Oncology Group (E2100). Breast Cancer Res Treat. 2005;94:S6.Google Scholar
22. Moher, D. Reporting research results: A moral obligation for all researchers. Can J Anesth. 2007;54:331–335.CrossRefGoogle Scholar
23. Moinpour, C, Wu, J, Donaldson, G, et al. Gemcitabine plus paclitaxel (GT) versus paclitaxel (T) as first-line treatment for anthracycline pre-treated metastatic breast cancer (MBC): Quality of life (QoL) and pain palliation results from the global phase III study. J Clin Oncol. 2004;22:32S.CrossRefGoogle Scholar
24. Montori, VM, Devereaux, PJ, Adhikari, NKJ, et al. Randomized trials stopped early for benefit: A systematic review. JAMA. 2005;294:2203–2209.CrossRefGoogle ScholarPubMed
25. Nabholtz, J, Pienkouski, T, Mackey, J, et al. Phase III trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) with FAC (5-fluorouracil, doxourbicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer (BC) patients: Interim analysis of the BCIRG 001 study. Proc Am Soc Clin Oncol. 2002;21:A141.Google Scholar
26. O'Shaughnessy, J. Developments in the systemic therapy of early-stage breast cancer. Eur J Cancer Suppl. 2007;5:3–10.CrossRefGoogle Scholar
27. O'Shaughnessy, J, Nag, S, Calderillo-Ruiz, G, et al. Gemcitabine plus paclitaxel (GT) versus paclitaxel (T) as first-line treatment for anthracycline pre-treated metastatic breast cancer (MBC): Interim results of a global phase III study [abstract 25]. ASCO. 2003;22:7.Google Scholar
28. Overmoyer, B, Silverman, P, Leeming, R, et al. Phase II trial of neoadjuvant docetaxel with or without bevacizumab in patients with locally advanced breast cancer. J Clin Oncol. 2004;22 (Suppl):727.CrossRefGoogle Scholar
29. Overmoyer, B, Silverman, P, Leeming, R, et al. Phase II trial of neoadjuvant docetaxel with or without bevacizumab in patients with locally advanced breast cancer. Breast Cancer Res Treat. 2004;88:S106.Google Scholar
30. Piccart-Gebhart, MJ, Procter, M, Leyland-Jones, B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–1672.CrossRefGoogle ScholarPubMed
31. Sartor, CI, Fitzgerald, F, Laurie, B, et al. Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control for node positive breast cancer in CALGB 9344. Proc Am Soc Clin Oncol. 2003;22:30–40.Google Scholar
32. Sartor, CI, Peterson, BL, Woolf, S, et al. Effect of addition of adjuvant paclitaxel on radiotherapy delivery and locoregional control of node-positive breast cancer: Cancer and leukemia group B 9344. J Clin Oncol. 2005;23:5–7.CrossRefGoogle ScholarPubMed
33. Scherer, R, Langenberg, P. von Elm E. Full publication of results initially presented in abstracts. Cochrane Database Syst Rev. 2007;2.Google Scholar
34. Schrag, D. The price tag on progress – chemotherapy for colorectal cancer. N Engl J Med. 2004;351:317–319.CrossRefGoogle ScholarPubMed
35. Sherrill, B, Allshouse, A, Amonkar, M, et al. A quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis comparing lapatinib plus capecitabine compared to capecitabine for metastatic breast cancer (MBC). J Clin Oncol. 2007;25:A18.CrossRefGoogle Scholar
36. Shields, PG. Publication bias is a scientific problem with adverse ethical outcomes: The case for a section for null results. Cancer Epidemiol Biomarkers Prev. 2000;9:771–772.Google ScholarPubMed
37. Slamon, D, Eiermann, W, Robert, N, et al. Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC (R) T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC (R) TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2 positive early breast cancer patients: BCIRG 006 study. Breast Cancer Res Treat. 2005;94:S5.Google Scholar
38. Slamon, DJ. Second interim efficacy analysis of the BCIRG 006 trial: Adjuvant chemotherapy with or without trastuzumab in HER2-overexpressing breast cancer. Clin Breast Cancer. 2007;7:449–450.Google Scholar
39. Smith, I, Procter, M, Gelber, RD, et al. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomised controlled trial. Lancet. 2007;369:29–36.CrossRefGoogle ScholarPubMed
40. Smith, IE; on behalf of the HERA study team. Trastuzumab following adjuvant chemotherapy in HER2-positive early breast cancer (HERA trial): Disease-free and overall survival after 2 year median follow-up. ASCO. 2006; Scientific Special Session.Google Scholar
41. Spielmann, M, Roche, H, Delozier, T, et al. Safety analysis from PACS 04: A phase III trial comparing 6 cycles of FEC100 with 6 cycles of ET75 for node-positive early breast cancer patients, followed by sequential trastuzumab in HER2+ patients: Preliminary results. J Clin Oncol. 2006;24:632.CrossRefGoogle Scholar
42. Takeda, A, Loveman, E, Harris, P, et al. Time to full publication of studies of novel chemotherapy drugs for breast cancer, and the potential for publication bias. HTA. 2008;12:1–68.Google Scholar
43. The HERA study team. Trastuzumab (H: Herceptin (R)) following adjuvant chemotherapy (CT) significantly improves disease-free survival (DFS) in early breast cancer (BC) with HER2 overexpression: The HERA Trial. Breast Cancer Res Treat. 2005;94:S9.Google Scholar
44. Trotta, F, Apolone, G, Garattini, S, et al. Stopping a trial early in oncology: For patients or for industry? Ann Oncol. 2008;19:1347–1353.CrossRefGoogle ScholarPubMed
45. Von Minckwitz, G, Raab, G, Schuette, M, et al. Dose-dense versus sequential adriamcycin / docetaxel combination as preoperative chemotherapy (pCHT) in operable breast cancer (T2-3, N0-2,M0)—primary endpoint analysis of the GEPARDUO-Study. Proc Am Soc Clin Oncol. 2002;21:A168.Google Scholar
46. Wagner, LI, Wang, M, Miller, K, et al. Health-related quality of life among patients with metastatic breast cancer receiving paclitaxel versus paclitaxel plus bevacizumab: Results from the eastern cooperative oncology group (ECOG) study E2100. Breast Cancer Res Treat. 2006;100:S239.Google Scholar
47. Wakelee, H. In focus: Non-small cell lung cancer: E1505. Clin Adv Hematol Oncol. 2007;5:206–207.Google Scholar