Highlights
- •Breast cancer trials are more inclusive than chronic disease trials.
- •Despite this, it was rare for more than 45% of women to be eligible.
- •Clinical and trial eligibility criteria are sometimes substantially different.
- •Many women receive treatments tested in trials for which they would be ineligible.
Abstract
Aim
To describe the proportion of women in Tayside, Scotland diagnosed with early breast
cancer who would have been eligible for influential adjuvant breast cancer trials.
Methods
Phase III trials of adjuvant treatment for breast cancer referenced in five national
guidelines were shortlisted by breast cancer specialists to identify the twelve considered
most influential. Eligibility criteria were extracted from protocols and applied to
a 16-year cohort of women who had received a diagnosis of breast cancer and the proportion
meeting trial criteria calculated. The criteria used clinically in Tayside to make
decisions about use of the trial treatments were also applied to the cohort. Finally,
the proportion of women receiving adjuvant endocrine therapy as part of their care
and who would have been eligible for the trial evaluating that therapy was calculated.
Results
Of the cohort’s 4811 women, 3535 (73%) were eligible for at least one trial but eligibility
for an individual trial rarely exceeded 45%. There were substantial differences between
the proportion of women meeting trial eligibility criteria and the proportion considered
clinically eligible for the same treatment. The proportion of women receiving an endocrine
therapy as part of their care who would also have been eligible for the trial evaluating
that treatment ranged from 17% to 56%.
Conclusion
Clinical eligibility criteria may be at variance with trial criteria. For adjuvant
endocrine therapy, a substantial proportion of women who would have been ineligible
for a trial nevertheless received the trial treatment as part of their care.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- External validity of randomised controlled trials: “to whom do the results of this trial apply?”.Lancet. 2005; 365: 82-93
- Explanatory and pragmatic attitudes in therapeutical trials.J Chronic Dis. 1967; 20: 637-648
- Making trials matter: pragmatic and explanatory trials and the problem of applicability.Trials. 2009; 10: 37
- External validity of randomised controlled trials in asthma: to whom do the results of the trials apply?.Thorax. 2007; 62: 219-223
- External validity of randomized controlled trials in COPD.Respir Med. 2007; 101: 1313-1320
- External validity of randomized controlled trials of glycaemic control and vascular disease: how representative are participants?.Diabet Med. 2013; 30: 300-308
- Are patients in clinical trials representative of the general population? Dose intensity and toxicities associated with FE100C-D chemotherapy in a non-trial population of node positive breast cancer patients compared with PACS-01 trial group.Eur J Cancer. 2011; 47: 215-220
- The guidelines manual.National Institute for Health and Clinical Excellence, London2009
- What kind of randomized trials do we need?.J Clin Epidemiol. 2009; 62: 461-463
- Factors that can affect the external validity of randomised controlled trials.PLoS Clin Trials. 2006; 1: e9
- Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy.JAMA. 2003; 290: 1624-1632
- Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer.Br J Cancer. 2008; 99: 1763-1768
- The importance of nonpharmacogenetic factors in endocrine therapy.Pharmacogenomics. 2012; 13: 721-728
- Early and locally advanced breast cancer: diagnosis and treatment National Institute for Health and Clinical Excellence guideline 2009.Clin Oncol (R Coll Radiol). 2009; 21: 159-160
- American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer.J Clin Oncol. 2010; 28: 3784-3796
- Fractionation for whole breast irradiation: an American Society for Radiation Oncology (ASTRO) evidence-based guideline.Int J Radiat Oncol Biol Phys. 2011; 81: 59-68
Scottish Intercollegiate Guidelines Network. SIGN 84 Management of breast cancer in women. A national clinical guideline. Scottish Intercollegiate Guidelines Network. Edinburgh 2005.
British Medical Journal. Best Practice: Primary invasive breast cancer. 2012 cited; Available from: <http://bestpractice.bmj.com/best-practice/monograph/716/treatment/step-by-step.html>.
- Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality.Br J Cancer. 2013; 108: 1515-1524
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383
- A comparison of systemic therapy utilization in British Columbia, Scotland, and Western Australia with models of “optimal” therapy.Breast. 2012; 21: 562-569
- (Arimidex, tamoxifen alone or in combination) trialists’ group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial.Lancet. 2002; 359: 2131-2139
- A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.N Engl J Med. 2005; 353: 2747-2757
- Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer.J Natl Cancer Inst. 2002; 94: 1143-1150
- Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation.N Engl J Med. 2001; 345: 1378-1387
- A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.N Engl J Med. 2004; 350: 1081-1092
- Randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer.N Engl J Med. 2003; 349: 1793-1802
- Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28.J Clin Oncol. 2005; 23: 3686-3696
- The UK Standardisation of Breast Radiotherapy (START) trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.Lancet Oncol. 2008; 9: 331-341
- The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.Lancet. 2008; 371: 1098-1107
- TACT Trial Management Group; tact trialists. sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomized controlled trial.Lancet. 2009; 373: 1681-1692
- Targeted intra-operative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A Trial): an international, prospective, randomized, non-inferiority phase 3 trial.Lancet. 2010; 376: 91-102
- Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomized phase 3 trial.Lancet. 2011; 377: 321-331
- ATAC Trialists’ Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer.Lancet. 2005; 365: 60-62
Eligibility criteria of randomized controlled trials published in high-impact general medical journals. JAMA 2007;297:1233–40.
- Assessment of differences in patient populations selected for or excluded from participation in clinical phase III acute myelogenous leukemia trials.J Clin Oncol. 2003; 21: 3933-3939
- Herceptin adjuvant (HERA) trial study team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.N Engl J Med. 2005; 353: 1659-1672
Article info
Publication history
Published online: April 07, 2015
Accepted:
January 13,
2015
Received:
January 13,
2015
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
