Clinical trial databases represent a potentially important tool for assessing compliance with recommended quality measures and determining the next quality measures of importance. ACOSOG is the most recent group to join the NCI-supported cancer cooperative trials group and represents a unique compilation of surgeons and institutions from across the United States. ACOSOG Z0010 is the largest prospective trial to date reported from this cooperative group. Patients registered on Z0010 came from a heterogenous set of institutions, none of which was preselected. However, skills verification requirements were necessary for participation by individual surgeons. There are currently 21 NCCN institutions nationwide, 14 of which enrolled patients onto Z0010. CoC-accredited hospitals are those that have met peer-reviewed guidelines for comprehensive, multidisciplinary cancer care. Sixty-seven percent of patients from Z0010 were treated in CoC-approved institutions. The CoC reports that approximately 75% of newly diagnosed cancer patients in the United States are treated within accredited locations.17
The Z0010 database therefore contains a representative sample of early-stage breast cancer patients treated both within large comprehensive cancer centers and those treated in local hospitals without a cancer-designated focus.
This study represents what is to our knowledge the first review of a clinical trials database to determine compliance with national quality measures in patients with breast cancer. The selected NQF measures, endorsed by ASCO and NCCN, reflect the outcomes of previous clinical trials showing a survival benefit for patients receiving adjuvant radiation, chemotherapy, and hormone therapy.18–20
Although teaching-affiliated hospitals represented the smallest subset of patients enrolled (22.7%) onto this trial, individuals treated at these locations had the highest rates of adjuvant radiotherapy (95.2%), adjuvant chemotherapy (7.9%), and adjuvant Tamoxifen therapy (81.6%). In addition, patients from these treating institutions had the lowest rates of excisional biopsy for diagnosis (28.6%). One possible explanation for this finding is that patients treated in these affiliated hospitals may be less likely to move between hospitals and providers, and their outcomes may be more centralized and retrievable. Although there were statistically significant differences in two NQF measures across institution types, they were very similar with respect to adherence to the reportable measures. The statistical differences are likely due to the large sample sizes available for the radiation and excisional biopsy measures within the ACOSOG Z0010 database.
Compliance with the first NQF measure, whole-breast radiotherapy, was the highest among all three institutional types (90.9–95%). Other reviews have shown similar rates of adherence to this quality measure. A recent analysis of the Medicare–Surveillance, Epidemiology, and End Results Program (SEER) database from 2000 to 2002 revealed 94% compliance with postoperative radiotherapy in 3674 women between the ages of 66 and 70.21
Data from eight NCCN centers collected between 1997 and 2002 revealed a 94% compliance with radiation recommendations for patients with stage I or II breast cancer.22
Statistically significant factors in this data set associated with a lower use of radiation included comorbid illnesses, tubular histology, type of health insurance, and actual NCCN institution. Although our patient population included only 135 patients with Medicaid or lack of insurance coverage, there was a statistically significantly lower proportion of patients receiving radiotherapy in this subgroup. Perhaps a closer look at patients not receiving radiotherapy would help determine the obstacles for the compliance of recommended care.
The number of measurement points needed to assess the treatment of the breast cancer patient is unknown. Measures that show a high degree of compliance, such as radiotherapy after breast-conserving surgery, may not be cost-effective to continue to evaluate. However, the definition of “high” has not been established and may vary on the basis of the stakeholders involved. It is not known whether 100% compliance would be achievable. The National Initiative for Cancer Care Quality (NICCQ) led by ASCO developed a set of 36 breast cancer measures through expert review of established guidelines, review articles, and randomized, controlled trials. Through patient surveys and medical record review, NICCQ documented <85% compliance with 18 of 36 measures.11
This ACO-SOG Z0010 data review identified a similarly moderate (80–81%) compliance with two of the recommended measures, chemotherapy for endocrine nonresponsive tumors and hormone therapy for those with endocrine-responsive disease. The NICCQ outcomes revealed a wide range of compliance with chemotherapy (60–91%) and a smaller range for hormone therapy (85–95%).11
Explanations for lower compliance rates in each of these data sets include the difficulty in assessing the patients’ understanding of the recommendations and/or desire to avoid side effects from adjuvant therapy and their comorbid illnesses that may have affected the ability of their providers to offer and administer additional treatment. Future quality-of-life outcome studies may help in better understanding the noncompliance with these measures.
In an international trial of 1378 breast cancer patients treated from 1998 to 2005, Cheng and colleagues found that 100% adherence to 10 quality indicators offered statistical improvements in overall survival (hazard ratio, 0.46) in comparison to those patients who did not have 100% compliance.7
Included in the 10 quality measures were radiotherapy for breast-conservation patients and hormone therapy for patients with endocrine-responsive disease. Chemotherapy was recommended only for patients aged <50 with node-positive disease. Patients with stage I disease in this subset (479) had a 5-year progression-free survival of 93% if they had 100% adherence versus 87% for <100% adherence to 10 quality measures. The ability to have 100% adherence will be dependent on the health care delivery system, its financial structure, the patients’ and physicians’ biases and preferences, and behavioral practices within the community itself.7
The only system evaluating the use of clinical trials as a benchmark of quality care is the voluntary reporting system developed in Germany.9
A nationwide breast cancer quality-care initiative was developed in 2002 and tracked yearly until the most recent publication in 2007. Eleven quality indicators were recorded, and over time, each showed improvement in patient compliance. Interestingly, adherence was high for endocrine therapy use (93%), while compliance with chemotherapy had a progressive increase from 65 to 81% with tracking and feedback to the institutions. The established benchmark for patients to be enrolled onto clinical trials is 10–20%, and 7% of patients met this measure in 2007 in Germany. Currently, there are no reported breast cancer measuring systems in the United States that use clinical trial enrollment as a marker of quality care.
There are limitations to this secondary review of a prospective clinical trial’s database. Only one of the NQF quality measures was included as an integral part of the Z0010 trial (radiation after breast-conserving surgery). In addition, there was patient movement between institutions. Some patients may have had their surgery at one location and follow-up at another outpatient clinic. The complete record of adjuvant treatments administered may not have been identified by the enrolling surgeon. Additionally, this data set reflects the care received 18 months after registration. We are unable to definitely prove that the radiotherapy was provided within the recommended 12 months or that the chemotherapy, if indicated, was started within the 4-month window after surgery. As with any database, we are limited by what we are asking and how diligent the investigators are in retrieving and reporting accurate data. Fortunately, these data are audited, and although every patient encounter cannot be reviewed, many are, and they are then compared to source documentation to assure compliance within the clinical trial protocol guidelines.
Unlike other medical conditions, the outcomes for patients with cancer have been recorded for over three decades in cancer registries as well as clinical trial databases. Patients within cancer clinical trials have helped to establish the current quality of care measures. As more patients are treated with novel therapies, undergo evaluation with genomic predictors, and are diagnosed with innovative imaging techniques, the quality measures will continue to change. The patients enrolled onto the Z0010 trial showed a high degree of compliance with quality standards that were not yet defined at the time they received treatment. Clinical trial databases afford another means to evaluate our current standards and the patient populations/institutions that may benefit the most from quality review and education. Further trials exploring NQF measures are warranted to better assess the overall impact of the measures on patient care.