BRIEF COMMUNICATION

High Rate of Consent to Bank Biologic Samples for Future Research: The Eastern Cooperative Oncology Group Experience

Thomas Malone, Paul J. Catalano, Peter J. O'Dwyer, Bruce Giantonio

Affiliations of authors: T. Malone, Eastern Cooperative Oncology Group, Boston, MA; P. J. Catalano, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston; P. J. O'Dwyer, B. Giantonio, University of Pennsylvania, Philadelphia.

Correspondence to: Thomas Malone, M.P.A., Eastern Cooperative Oncology Group, 900 Commonwealth Ave., 2nd Floor, Boston, MA 02215 (e-mail: tmalone{at}partners.org).

ABSTRACT

The Eastern Cooperative Oncology Group (ECOG) requires patient consent for the storage and future use of samples left over from its therapeutic cancer clinical trials. The ECOG consent instrument evolved from a simple statement requiring a signature to a more detailed three-question format. Between February 1998 and October 2000, more than 7000 patients were accrued to studies using one of the two consent forms. We analyzed our consent response data by consent type, demographic information, disease site, and institution type to determine the assent rates for future storage and research on biologic samples and to identify possible factors predicting patient refusal. The assent rate for the original banking consent statement was 89.4%, whereas that for the more detailed consent form was 93.7%. Higher assent rates were statistically significant for the detailed consent form versus the original consent form (P= .001), for community-based practices versus academic centers (P<.001), and for patients aged at least 65 years versus those younger (P= .002). The results show that increased patient protection does not result in decreased availability of biologic samples for future research purposes.


There has been great debate over the extent of patient consent documentation required to conduct research on stored biologic samples (1). The value of these samples as a resource to academic and commercial researchers has never been greater, particularly with the availability of the human genome sequence and the focus on targeted therapies. The public discourse resulting from scientific advances over the last decade has led to a heightened awareness of the possible uses of research on an individual's samples and the potential for harm (2). In 1999, the National Bioethics Advisory Commission issued recommendations making it clear that appropriate consent is needed for future use of collected human biologic samples (3).

The Eastern Cooperative Oncology Group (ECOG) has routinely collected biologic specimens from cancer patients participating in therapeutic clinical trials for both diagnostic and correlative research purposes. The need for patient protection regarding the use of stored biologic materials for research resulted in a policy within ECOG requiring specific consent for the collection, storage, and future use of biologic specimens from 1998 forward. The first consent instrument adopted for this purpose consisted of a one-paragraph statement (available at the Journal's web site: http://jncicancerspectrum.oupjournals.org) that was appended to the therapeutic trial consent form. A separate signature was required following this paragraph to acknowledge patient consent. This paragraph, approved by the National Cancer Institute, was added to existing and newly activated trials involving the collection of biologic specimens. The ECOG Coordinating Center collects the consent response at the time of patient registration to the therapeutic trial and communicates it to the ECOG tissue repositories to ensure that samples are not released for research without appropriate consent.

In May 1999, the Intergroup Specimen Banking Committee (ISBC) released guidelines for the collection, storage, and distribution of patient specimens from Intergroup trials (4). In these guidelines, the Committee recommended that the National Action Plan for Breast Cancer (NAPBC) model consent form be used as a template for obtaining informed consent for the use of stored biologic samples in cooperative group research. This recommendation expanded the information provided to the patient relative to that provided by the ECOG's original specimen banking statement. The recommendation included the addition of three specific yes-or-no questions (Table 1Go) that allowed patients to designate the level of research to be performed on their specimens (detailed recommendation available at the Journal's web site: http://jncicancerspectrum.oupjournals.org). In the fall of 1999, ECOG adopted this consent template only for all newly activated trials that collected biologic samples, because ECOG did not want to change the original consent instrument already in use in active trials.


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Table 1. ECOG assent rate for future research on biologic samples by form type*
 
We analyzed the consent responses from all patients accrued to ECOG studies that obtained biologic samples between February 1998 and October 2000 to determine the willingness of patients to provide for unspecified future research on their stored biologic samples and to identify factors predicting patient refusal. The responses were analyzed by demographics, disease site, and ECOG institution type. ECOG institution type was defined as main institution (academic hospital or cancer center), Cancer Group Outreach Program (CGOP) members (community hospitals and private practices affiliated with an academic member), and Community Clinical Oncology Program (CCOP) members (network of community hospitals or practicing physicians that share research resources).

By October 31, 2000, 5411 patients were registered to 40 ECOG coordinated trials that used the original consent paragraph for tissue banking, and 2154 patients were registered to seven trials that used the newer modified (ISBC-revised) consent form, with the three additional questions. Both consent forms had a high rate of assent: 89.4% of patients signed the original ECOG consent form, 93.7% of patients approved question 1 (Q1) of the ISBC-revised consent form, 86.9% approved Q2, and 84.3% approved Q3 (Table 1Go). Comparing the response rate to Q1 with the response rate to Q2 of the ISBC-revised consent form, the willingness to allow future research specific for cancer versus other types of diseases was highly statistically significant (P<.001, McNemar's Test; SAS version 8; SAS Institute, Cary, NC). Comparing ECOG's original consent paragraph with Q1 of the ISBC-revised consent form also revealed a higher acceptance rate of the new form (93.7% versus 89.4%; P<.001). These data demonstrate a high rate of consent for future research use of stored biologic samples among cancer patients participating in clinical trials.

Patient sex or disease site had no effect on consent rates, regardless of which consent form was used. It is important to point out, however, that a substantial number of the consent forms analyzed came from women who participated in two adjuvant chemotherapy trials in breast cancer (Table 2Go). The original ECOG consent form was used for one trial and the ISBC-revised consent form was used for the other. Among patients who signed the original ECOG consent form, there was a statistically significantly higher assent rate by patients aged 65 years or older compared with those younger than 65 years (92.1% versus 88.7%; P<.001). Among patients who signed the ISBC-revised consent form, there was no statistically significant difference between patient age groups, possibly because of a lack of statistical power (Table 2, AGo).


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Table 2. Factors predicting assent rates for patients enrolled in ECOG clinical trials
 
The type of institution enrolling the patient was a factor in determining consent rates. Main institutions had a statistically significantly lower acceptance rate to the original consent form (83.3%) than did CGOP institutions (91.5%; P<.001) and CCOP institutions (95.6%; P<.001). The CCOP acceptance rate was also statistically significantly higher than that for CGOP institutions (P<.001). All three institution types had higher acceptance rates with the ISBC-revised consent form than with the original consent form; however, the differences among the acceptance rates relative to the institution type remained, with statistically significant differences for the comparison between the main institutions and CGOPs or CCOPs (P<.001 for both). Comparing acceptance rates for the ISBC-revised consent form between CGOPs and CCOPs did not reveal a statistically significant difference.

A multivariate analysis with logistic regression found that the following factors predicted consent to bank biologic specimens and use them in future research: using the consent form that followed the NAPBC model (P = .001), being 65 years of age or older (P = .002), and enrolling at a non-main institution (P<.001) (Table 2, BGo).

Several explanations may account for the differences in assent rates among the subgroups. First, variation in the conduct of the consent process is likely to exist among different institutions. This could include region-specific requirements for the format and content of the consent form, and the time and personnel devoted to reviewing information with the patient. Second, there may be differences in the economic and educational level of individuals among the various types of institutions, and multilingual communities may have language limitations. Third, the high assent rate among patients aged 65 years or older may reflect a greater sense of societal responsibility that influences a willingness to provide consent (5) or, alternatively, a willingness to accede to the recommendations of their physicians.

Although there may be differences among individuals in the subgroups that were analyzed, a variable of likely importance, albeit one more difficult for study, is the influence of a patient's a priori beliefs on the merits and risks of clinical research. Thus, the manner in which information is verbally communicated to the patient, especially those who might view clinical research with suspicion, may have a greater effect on patient decision making than does the content of the consent form itself.

We find these results encouraging, because they suggest that efforts at increased patient protection do not result in decreased availability of biologic samples for research purposes. Although many cancer patients who participate in clinical trials support the storage of biologic specimens for future unspecified research, it will be important to know consent rates from noncancer patients, which could provide a broader picture of patients' willingness to allow their samples to be used for future research. Our findings may serve as a baseline for future analyses as the consent process for the storage and use of biologic specimens continues to evolve.

NOTES

This study was conducted by the Eastern Cooperative Oncology Group and was supported in part by Public Health Service grants CA21115 and CA37403 (to Robert L. Comis, M.D.), CA66636 (to Robert Gray, Ph.D.), and CA15488 (to Daniel Haller, M.D.) from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

REFERENCES

1 Weir, RF. The ongoing debate about stored tissue samples, research, and informed consent. In: National bioethics advisory commission: research involving human biological materials: ethical issues and policy guidance, Vol 2. Rockville (MD): U.S. Government Printing Office; 1999. p. F1–F21. Available from: http://bioethics.georgetown.edu/nbac/hbmII.pdf.

2 Andrews L, Nelkin D. Whose body is it anyway? Disputes over body tissue in a biotechnology age. Lancet 1998;351:53–7.[Medline]

3 National Bioethics Advisory Commission. Research involving human biological materials: ethical issues and policy guidance. Vol 1. Rockville (MD): U.S. Government Printing Office; 1999. Available from: http://bioethics.georgetown.edu/nbac/hbm.pdf.

4 Report of the Intergroup Specimen Banking Committee. May 31, 1999. Unpublished.

5 Kaye JM, Lawton P, Kaye D. Attitudes of elderly people about clinical research on aging. Gerontologist 1990;30:100–6.[Abstract]

Manuscript received September 21, 2001; revised February 28, 2002; accepted March 6, 2002.


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