Abstract
Background Requiring written informed consent for a minimal-risk survey may result in limited participation rates.
Methods Data from a cross-sectional survey of 177 older patients (87 blacks and 90 whites) with hypertension enrolled in the managed care Medicare risk product were used to assess participation rates pre- and postwaiver of written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization. Prior to the waivers being granted, patients were contacted two times via mail with an introductory letter and an informed consent document. Those who completed and returned the informed consent document were administered the questionnaire. After 6 weeks, a waiver of written informed consent and HIPAA authorization was obtained from the Institutional Review Board. Nonparticipants were reapproached and asked to complete the questionnaire. Participation rates were recorded before and after receiving the waivers.
Results Participation rates increased from 21.5% in the prewaiver period to 57.4% in the postwaiver period (p < .001). Prewaiver participation differed by demographic subgroup and was higher among whites (26.7%) versus blacks (16.1%; p = .087), men (31.6%) versus women (16.7%; p = .024), and participants ≥ 75 years old (28.4%) versus < 75 years old (14.6%; p = .025). In contrast, the postwaiver participation rate did not differ significantly across race, gender, or age subgroupings. Significant increases in participation rates from the pre- to the postwaiver time period were noted within each demographic subgroup (all p < .01).
Conclusions We identified a substantial increase in participation rates postwaiver of written informed consent and HIPAA authorization in a minimal-risk survey. The need for written documentation for minimal-risk surveys may negatively impact recruitment of blacks, women, and patients < 75 years old.
Few studies have reported the effects of written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization requirements on participation rates in minimal-risk survey research. Requiring written permission before contacting potential research participants or mandating written consent for medical record review research has been reported to be associated with low response rates.1,2For example, Nelson and colleagues found that requiring advance permission to obtain informed consent from patients reduced participation rates in studies, especially at sites requiring written authorization.3In recent years, increasing attention has been given to the importance of human subjects' protection in general and to the informed consent process specifically.4The purpose of the current study was to compare participation rates in a minimal-risk survey among older patients with hypertension from before to after waivers of written informed consent and HIPAA authorization were granted from our Institutional Review Board (IRB).
METHODS
Parent Study Population and Design
The foundation for the current study was derived from the experience of conducting a survey of factors associated with antihypertensive medication adherence. The survey included questions regarding patient demographics, antihypertensive medication adherence, lifestyle modification related to a previous diagnosis of hypertension, complementary and alternative medicine use, quality of life, sexual functioning, satisfaction with access to care, and communication with their health care provider. The survey took approximately 30 minutes to complete. An additional goal of the parent study was to compare survey participation rates via mail versus telephone. As such, participants were randomized on a 1:1 ratio to complete the survey via mail or by telephone. In preparation for the research study, we collaborated with the managed care organization to identify and contact patients potentially eligible for the study through the organization's administrative data systems.
Using stratified block sampling, 200 study participants were randomly selected from the administrative database based on the following inclusion criteria: member of the Medicare risk product, 100 black patients and 100 white patients, at least two documented encounters with a primary or secondary diagnosis of essential hypertension (International Classification of Disease-9th revision code 401.XX as recorded in the managed care organization's administrative database), and continuously enrolled in the managed care organization for at least 1 year at the time of study participation. After excluding 23 patients (incapacitated n = 8, invalid contact information n = 13, institutionalized n = 2), 177 patients were eligible for the survey.
Survey Methodology
Approval for the conduct of the survey with written informed consent was obtained from the Ochsner Clinic Foundation's IRB on November 24, 2002. The study was conducted under the requirement of completion of written informed consent from December 2002 through January 2003. During this time period (prewaiver), patients were mailed an initial introductory letter from the medical director of the managed care organization and the principal investigator of the study, along with an informed consent document. The introductory letter described the purpose of the study, the confidentiality of responses if the patient chose to participate, the request to return the signed informed consent document, and investigator contact information. The informed consent document detailed the specifics of the study, including the potential risks and benefits. When patients returned the signed informed consent document, they were contacted by mail or telephone by trained research staff and asked to complete the survey. Participants who did not return an informed consent document within 4 weeks were resent an introductory letter and consent form. Owing to the low participation rates, waivers of written informed consent and HIPAA authorization were sought and obtained from the IRB on January 29, 2003. After excluding persons who completed the survey (n = 38) or refused participation (n = 3), eligible participants (n = 136) were recontacted by mail or telephone according to the random assignment described above and were asked to participate in the study by completing the survey.
Statistical Methods
Participation rates were calculated for the overall study population and by age group (< 75 or ≥ 75 years of age, the median age of the study population), gender, race (white or black), and mode of administration (mail or telephone). Differences in participation rates across subgrouping were assessed using a two-sided chi-square test. For the remainder of the analyses, each participant was given one or two records in the study database. Patients who agreed to participate prior to the study being granted the waivers were given one record representing the prewaiver period. Likewise, patients who refused participation and asked not to be contacted again were given one record in the study database representing the prewaiver period. Patients who did not agree and did not refuse to participate during the period prior to the waivers being granted had two records. The first record reflected nonparticipation in the period prior to the waivers. The second record reflected the period subsequent to the waivers. Participation rates were calculated for each time period (ie, prior to and subsequent to waiver of written informed consent and HIPAA authorization) for the overall study population and by age group, gender, race, and mode of administration. Chi-square tests were used to determine differences in the participation rates across subgroupings within the prewaiver period and the postwaiver period separately. Logistic regression models that took into account the clustering of observations (ie, two records being present for some individuals) were used to compare the significance of the changes in participation rates within age, race, and gender subgroups from the prewaiver to the postwaiver period. Next, a multivariable logistic regression model was used to determine whether differences in participation rates across age, race, and gender subgroups, separately, changed significantly from the prewaiver to the postwaiver period. This regression model included main effect terms for study period (pre- or postwaiver), age group, gender, race, and three separate interaction terms: study period by (1) age group, (2) gender, and (3) race. The p value for each interaction term (eg, race by study period) was used as a measure of significance for the change in the differences in participation rate across subgroups from the prewaiver to the postwaiver period. All analyses were performed using Stata, version 7.0, software (Stata Corporation, College Station, TX).
RESULTS
Of the 177 potential study participants, the median age was 75 years (range 53-93 years), 32% were men, and 49% were black. Overall, 116 people completed the survey, yielding a participation rate of 65.5% (Table 1). Participation rates in the survey were significantly higher among persons ≥ 75 years of age (p = .008) and were nonsignificantly higher among females and whites. Participation rates were 62% for those randomized to complete the survey by mail and 71% for patients assigned to complete the survey by telephone (p = .25).
The participation rate increased from 21.5% (n = 38 of 177 eligible patients) during the prewaiver time period to 57.4% (n = 78 of 136 patients) during the postwaiver time period (p < .001). Prewaiver participation rates differed by demographic subgroup and were 14.6% and 28.4% among patients < 75 years old and ≥ 75 years old, respectively (p = .025); 16.7% and 31.6% among women and men, respectively (p = .024); and 16.1% and 26.7% among blacks and whites, respectively (Figure 1; p = .087). Significantly higher participation rates were observed in the postwaiver compared with the pre-waiver time period (all p < .01). The postwaiver participation rates did not differ significantly within any of the subgroups. Specifically, after being granted a waiver of written informed consent and HIPAA authorization, participation rates were 50.7% and 65.1% among participants < 75 years old and ≥ 75 years old (p = .091), respectively, 61.2% and 47.4% among women and men (p = .143), respectively, and 55.7% and 59.1% among blacks and whites (p = .691), respectively. A significant period by gender interaction was present; men were more likely to participate before the waivers were granted, whereas women were more likely to participate after the waivers were granted (p interaction = .012). The difference in participation rates between blacks and whites was substantially smaller in the postwaiver period compared with the prewaiver period. However, this change was not statistically significant (p interaction = .481). The difference in participation rates for patients < 75 years versus ≥ 75 years was similar in the pre- and postwaiver time periods (p interaction = .975).
DISCUSSION
Requiring written informed consent and HIPAA authorization in a minimal-risk survey of older patients with hypertension resulted in a response rate of only 21.5%. This low participation rate occurred despite two attempts to contact patients and garner written informed consent. Once the study was granted a waiver of written informed consent and HIPAA authorization from the IRB, 57.4% of patients who had not returned the informed consent previously were willing to complete the survey either by telephone or by mail. Overall, we identified a substantial increase in participation rates of 21.5 to 57.4% from pre- to postwaivers of written informed consent and HIPAA authorization.
Other studies have documented low response rates when written informed consent was required for medical record review2or when a return postcard was required before contacting a patient for a health-related survey (response rates 19% and < 30%, respectively).1In 2003, Angus and colleagues conducted an analysis of individuals who were first contacted by mail to achieve consent and were subsequently assigned to receive a mailed or electronic survey for completion.5Only 25% of the eligible individuals returned the signed consent form and were invited to complete the survey; the overall survey response rate (completed surveys returned) was only 20%. Nelson and colleagues noted that stringent policies regarding the contact of potential participants can threaten the validity of research results.3In our study, a response rate of 21.5% before waiver of written informed consent and HIPAA authorization would have been inadequate to draw conclusions about the health status of older patients with hypertension.
In addition to the overall low response rate encountered in our study, the need for written informed consent and HIPAA authorization resulted in lower participation among black patients, women, and persons < 75 years of age. The differences in demographic characteristics between those who responded pre- and postwaiver revealed a potential selection bias, which may negatively impact scientific validity. Other minimal-risk studies have reported differences in participation by race, gender, and age when written informed consent processes are required. Yawn and colleagues reported higher study refusal rates among women when written authorization or consent was required prior to review of medical records.6They noted that this “authorization bias” could distort outcomes data.6Consistent with the results of the present study, Woolf and colleagues reported that older patients, men, and whites were more willing to give consent to be contacted for a health assessment survey or for medical record review.7Thus, it is likely that patients willing to provide written informed consent may differ in important respects from those who are not. In such cases, conclusions based on the subset of responders have the potential to mischaracterize the health status of the larger population.7One of the best ways to reduce biases caused by nonparticipation is to increase participation rates.8The results of our study suggest that when conducting minimal-risk survey research, a waiver of written informed consent and HIPAA authorization from the IRB may be a key element for achieving sufficient response rates. A waiver of the written process does not provide investigators with a waiver of the responsibility to fully inform potential participants and to maintain the confidentiality and privacy of all patient data. For example, even after obtaining a waiver of informed consent, patients in the current study were informed of the purpose of the study, survey questions, and confidentiality of the data being collected.
Title 45 of the Code of Federal Regulations part 46 (45 CFR 46) is the human subject protection regulations enforced by the Office of Human Research Protections.9These are the Department of Health and Human Services' regulations that mandate IRB review and informed consent for federally funded research. Most institutions extend these requirements to all human subject research regardless of funding source. The regulations have more flexibility than many realize.
Adult survey research can be exempt from IRB review under 45 CFR 46.101(b)(2) unless both of the following apply:
information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to the subjects; and; and
any disclosure of a human subjects' responses outside the research endeavor could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation.9”
Exempt research means exempt from the regulations at 45 CFR 46 that mandate IRB review and informed consent.9If a study is judged to be exempt research, then an informed consent document is not required. Surveys involving the collection of sensitive information that maintain patient identifiers would not qualify under the exempt regulations. Research involving pregnant women, fetuses, human in vitro fertilization, or prisoners is excluded from exempt research by an official footnote to this regulation.9However, the appropriate institutional authority, often the IRB chair or a research committee, must make this decision.
To be conducted, nonexempt research must obtain IRB approval if federally funded or if the institution has applied these principles to all human subject research. Written informed consent is required unless the following conditions are met for a waiver (Title 45 CFR 46.116(d)):
“The research involves no more than minimal risk to the subjects; The waiver or alteration will not adversely affect the rights and welfare of the subjects; The research could not practicably be carried out without the waiver or alteration; and Whenever appropriate, the subjects will be provided with additional pertinent information after participation.9”
Item (3) is usually a debatable point and requires interpretation by the IRB. If evidence can be presented that informed consent will “practicably” make the research impossible owing to dramatically reduced response rates that render the study invalid, then an IRB might reasonably determine that a waiver of written informed consent is justified under the regulations. This will vary depending on the details of the study, an IRB's perception of risk, and the manner in which the local IRB interprets this regulation.
Investigators conducting nonexempt research for which informed consent is not waived may have documentation of informed consent waived by the IRB in the following situations (45 CFR 46.117(c)):
An IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either:
the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality. Each subject will be asked whether the subject wants documentation linking the subject with the research, and the subject's wishes will govern; or
the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context.9”
Waiver of documentation of consent means that there is no requirement for a signed consent form, but the requirement for a consent process, such as a verbal consent discussion on the telephone, remains intact. In the present study, all patients were informed in writing about the purpose of the study, the content of the survey questions, the potential risks and benefits of the study, and commitment to maintaining the confidentiality of the data. In the postwaiver period, all patients were given access to the full survey (either by mail or by telephone) and the opportunity to voluntarily complete the survey.
In conducting minimal-risk survey research, there are several options in complying with regulatory requirements. First, one should explore if the research qualifies as exempt. If not, then the investigator could provide information to the IRB for determination of waiver of informed consent or simplification of informed consent into a brief script along with a waiver of documentation of consent. Finally, if the waiver of informed consent does not apply in a nonexempt study, the investigator may consider whether a waiver of documentation of informed consent is appropriate. Others have recommended that IRBs provide simplified forms for this type of research.10
HIPAA research authorization under the privacy rule is another regulatory requirement for a covered entity. There are detailed documents on HIPAA regulations in research (see <http://privacyruleandresearch.nih.gov/>) and in minimal-risk research. Key issues to be aware of include the following:
Most IRBs will waive the HIPAA authorization requirements when conditions for waiver of informed consent are present. The requirements for each IRB are a bit different, and additional information may be needed (eg, a HIPAA waiver form to fill out).
The HIPAA does not have a provision to waive documentation of an authorization that parallels the Common Rule's waiver of informed consent documentation. A complete HIPAA waiver should be requested if a waiver of documentation of informed consent applies.
If a consent form is required under the Common Rule, then an authorization form is likely required under the HIPAA. Some IRBs prefer that these documents be combined, whereas others prefer that they be separate documents.
Another Privacy Rule concern is how people included in the study are located, how their contact information is obtained, and how they are then approached for participation. Typically, this occurs prior to obtaining an authorization if one is required. The HIPAA allows for either a notice preparatory to research (if only workforce members will see protected health information or a partial HIPAA waiver for recruitment (when nonworkforce members may see protected health information) to cover this situation. It is a good practice, regardless of whether an authorization is required, to let subjects know how the information to contact them was obtained and what privacy protection measures are being used. In our study, we collaborated with a managed care organization to identify patients. Patients were informed that all responses would be kept confidential.
LIMITATIONS
The results of the current study should be interpreted in the context of its limitations. Although the informed consent document was targeted for patients with at least an eighth-grade reading level, the reading level and cultural orientation of the document may have dissuaded patients with limited education from participating. In addition, the introductory letter and consent form were mailed to the home; these documents may have been lost or received by someone else in the household who opted not to forward the information to the intended recipient. The external validity, the extent to which our findings may be extrapolated beyond our outpatient population, may also be limited. To be eligible, patients were required to have had at least two visits with a diagnosis of hypertension in a large multispecialty clinic as part of a large southern managed care organization. It is possible that patients' willingness to provide written informed consent may differ in other settings. Studies by Yawn and colleagues and Woolf and colleagues described the characteristics of patients in different settings who did and did not give written informed consent for various research studies.6,7Although there were some differences in patient characteristics and study designs, the previous results were similar to those we are reporting: patients who are willing to provide written informed consent differ in important demographic characteristics from patients who do not provide written informed consent. Finally, we cannot be certain that the temporal increase in response rates from the prewaiver to the postwaiver time period was due to the informed consent and HIPAA authorization waivers alone and not due to making a third contact with the potential study participants.
CONCLUSIONS
The current study extends previous results by examining the impact of receiving waivers for written informed consent and HIPAA authorization on response rates in a minimal-risk study. The waiver of informed consent and HIPAA authorization resulted not only in a significant increase in response rates but also in the reduction of demographic differences in response rates after waiver of written documentation. It is important to realize that waiver of written informed consent and HIPAA authorization does not diminish the investigators' responsibility regarding respect for the privacy and confidentiality of the patient or waive the patients' right to refuse to participate in the study.
The requirement for written informed consent and HIPAA authorization in minimal-risk survey studies may adversely impact the ability of investigators to conduct valid research. Although it is requisite for patients to be fully informed about the research study for which they are being asked to participate, our study results suggest that seeking a waiver of written informed consent and HIPAA authorization from the IRB may be important in conducting minimal-risk epidemiologic research.