Motivated by money? The impact of financial incentive for the research team on study recruitment.
Medicine, Experimental (Government finance)
Research ethics (Standards)
Research grants (Standards)
Research grants (Ethical aspects)
|Publication:||Name: IRB: Ethics & Human Research Publisher: Hastings Center Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 Hastings Center ISSN: 0193-7758|
|Issue:||Date: Jan-Feb, 2010 Source Volume: 32 Source Issue: 1|
|Topic:||Event Code: 900 Government expenditures; 350 Product standards, safety, & recalls; 290 Public affairs Advertising Code: 91 Ethics|
|Product:||Product Code: 8000200 Medical Research; 9105220 Health Research Programs; 8000240 Epilepsy & Muscle Disease R&D NAICS Code: 54171 Research and Development in the Physical, Engineering, and Life Sciences; 92312 Administration of Public Health Programs|
|Geographic:||Geographic Scope: Canada Geographic Code: 1CANA Canada|
Biomedical research is a very competitive arena. Investigators not
only compete for internal and external funding for their clinical
trials, but also for healthy people or patients to enroll in their
studies. Indeed, one of the largest obstacles investigators face is
getting people to enroll in their trials. (1) Thus, budgets for
conducting clinical trials increasingly include financial remuneration
to research participants; they might also include financial remuneration
to the research team.
Although studies have been conducted to determine whether payment to participate in research influences a person's decision to enroll in a study, (2) little is known about what motivates researchers to conduct and complete studies. One explanation is that researchers have the desire to contribute to medical knowledge with the hope that such knowledge will benefit future generations of patients. Other factors might include answering a specific research question, publishing the results of research in peer-reviewed journals, professional enhancement, and financial remuneration.
With the growth in industry sponsored clinical trials, there has been increasing concern about the ethics of financial remuneration for research-related activities. Although the impact of financial incentive on the research team has been perceived as important by industry and the public, the significance of this impact is unknown. (3) Media reports about industry payments to investigators with the headlines "Drug Trials Hide Conflicts for Doctors" (4) and "Bounty-Hunting Doctors Recruit Human Guinea Pigs" (5) reflect a negative view of such payment practices and suggest that researchers' financial ties to industry sponsors might compromise their obligations to trial participants. This was one of the issues that emerged from the investigation of the death of a young man involved in a gene transfer trial. (6)
Due to a fortuitous set of circumstances at our institution, we had the opportunity to explore the issue of financial remuneration to the research team for research-related activities. We examined whether financial remuneration to the research team in a neonatal intensive care unit (NICU) impacted either the rate at which the research team approached parents about research participation or the rate at which parents provided consent to participate.
Neonatology is an area of medicine with an intense amount of clinical research focusing on the extremely low birth weight infant. Clinical trials within NICUs often vie for the same population of patients, making trial recruitment a challenging activity. (7) Moreover, because parents or guardians are asked to enroll their newborn in a clinical trial at a time when they are experiencing great stress and anxiety as a result of the preterm birth, (8) they find decisions about trial participation difficult. Thus, one tactic to increase the number of patients enrolled in trials would be for the trial sponsor to provide financial remuneration to members of the research team for time spent in the recruitment process. The remuneration might only be provided if a patient or surrogate provides consent to participate.
We examined the recruitment and informed consent rates for two separate clinical trials with nearly identical inclusion criteria that were conducted concurrently in the NICU of a tertiary institution in Canada. Infants born at less than 1,250 grams (approximately 2.75 pounds) birth weight were eligible for entry into one of two randomized controlled trials. The trials--both of which were initiated by investigators--examined commonplace therapies designed to provide respiratory support for preterm newborns when they were close to being extubated. At the time the studies were conducted, the NICU had a policy that parents could be asked to enroll their newborn in only one interventional study during the infant's first week of life.
Study A was a multicentered, federally funded, placebo-controlled trial involving a medication that was the standard of care for treatment of newborns nearing extubation in order to prevent apnea of prematurity, an immature and irregular breathing pattern in preterm babies. Trial participation required parental consent and randomization within the first 10 days of life. For newborns not enrolled in the trial, the medication under investigation was routinely prescribed just prior to extubation. As a part of trial participation, parents were offered the opportunity to bring their child to the affiliated neonatal neurodevelopmental follow-up clinic until the child reached 18 months corrected age.
[FIGURE 1 OMITTED]
Study B was a single-center, unfunded trial involving two different forms of noninvasive respiratory support following extubation. The NICU had experience with both types of ventilation strategy, though one approach was the standard of care and the other was used infrequently. The only time requirement for enrollment was that participants be randomized prior to extubation.
Additionally, they all received research training from the physician-investigator, but none had taken a course or obtained a certificate in research ethics. Once parents gave consent for their newborn's participation, the attending neonatologist wrote the orders for the study medication or ventilation strategy.
For study A, members of the research team were financially compensated for their time by a predetermined amount only if they were successful in obtaining parental consent; thus, they obtained no compensation for time spent approaching parents who declined to enroll their newborn in the study. Payments were made to the collective research team and were used to send two members of that team to an international conference the following year. For study B, there was no financial compensation to the primary investigators or other members of the research team.
Parents were not informed that there was more than one study in which they could enroll their child. They were also unaware that if they gave consent for their child to participate in study A, the research team would be financially remunerated. At the time studies A and B were conducted, the institution did not require researchers to disclose in study information documents or consent forms that researchers would receive financial remuneration for enrolling patients in clinical trials.
The hospital research ethics board approved our study, which included approval for retrospective examination of the eligibility log books for studies A and B for the period of October 1, 2002, to October 1, 2003. We abstracted data from the log books for birth weight, gestational age, gender, study eligibility, approach, and consent. Due to the retrospective nature of our study, members of the research team were unaware when they approached parents for consent that their rate of approach would later be under investigation. Comparisons between the two studies were performed using the Mann-Whitney test for continuous variables and the chi-square or Fisher's exact test for categorical variables. McNemar's exact test was used to determine if the study type had an effect on approach rate. All analyses were done in SAS 9.1 (SAS Institute Inc., Cary, NC).
The eligibility criteria were identical for the two studies. Of approximately 1,000 admissions to the NICU in the year that comprised our study period, 84 newborns were eligible for both studies. For the purposes of this analysis, multiples were counted as a single unit, leaving 71 sets of parents who could be approached to enroll their newborn in study A or study B. The research team approached 43 (61%) of the parents to enroll their newborns in study A and 12 (17%) for study B. Of those approached for study A, 16 gave consent for trial participation. Of those approached for study B, all 12 gave consent for trial participation.
When examined as a proportion of the total number of newborns eligible to participate, consent was obtained from 21% of the parents whose newborns were eligible for study A and from 17% of the parents whose newborns were eligible for study B. When examined as a proportion of the total number of parents approached for trial participation, consent was obtained from 35% for study A and 100% of the parents approached for study B (Figure 1). There is a statistically significant difference between the approach rates for the two different studies (p < 0.0001). There is an opposing statistically significant difference between the consent rates for the two studies when considered as a proportion of those approached (p < 0.0001). The consent rate for study A at our institution was lower than the mean reported for other centers conducting the trial.
Our retrospective analysis suggests that the prospect of financial remuneration to the research team may have increased the rate at which parents were approached to enroll their newborn in a competitive research setting. The same research team was responsible for recruiting participants for two competing studies, though the team was financially compensated only when consent was obtained for one of the studies. During the recruitment process the research team was aware of the competition for trial participants. The respiratory therapists had responsibility for ensuring that eligible newborns had equal opportunity to participate in either trial. Nonetheless, the research team approached parents about enrolling their newborn in a trial at a higher rate for study A, which provided the team with financial remuneration, than for study B, which provided no remuneration. Interestingly however, the final number of newborns enrolled in each study was not significantly different. This is because parents were much more likely to agree to enroll their newborn in the study for which the team was not financially rewarded. Of note, the parents were unaware of how either study was financed, and there was no financial remuneration to parents who enrolled their child in a study. Furthermore, parents were not aware that their child was eligible for more than one trial.
There were many factors other than the remuneration plan--including trial design, parental acceptance of research participation, and aspects of the research team (e.g., team motivation, scientific curiosity, determination to succeed, and peer pressure)--that could have impacted how the research team approached parents about trial enrollment and whether the parents agreed to enroll their child in the trial presented to them. Although both trials enrolled preterm newborns about to be extubated, there were significant differences between the two trials. Study A was a placebo-controlled drug trial, and parents have reported greater reluctance to enroll their child in a trial that does not guarantee that the child will receive an active medication. (9) Study B examined the difference between two modes of respiratory support. Parents may have been more likely to consent to this trial because they did not understand the subtle differences between the two types of respiratory support or because they perceived the strategies to be a minor intervention. The requirement for long-term follow-up for study A was unlikely to have improved enrollment as there is national health care in Canada and, therefore, easy access to medical care. The follow-up requirement may in fact have scared some parents away from enrolling their newborn because of the long-term commitment for follow-up once the interventional part of the trial was over.
Although the respiratory therapists were trained by the physician-investigators about what information to provide during the informed consent process, they may have been more comfortable discussing the ventilation strategies involved in study B than the medications and their side effects involved in study A. Thus, from their perspective, there may have been a lower perception of risk associated with the study of ventilation strategies than with a study involving a medication. It's also possible that the presentation style of the research team may have been influenced by the possibility of financial remuneration. The team may have been circumspect in presenting information to the parents so as not to give the appearance that their attempt to obtain consent was motivated by money. On the other hand, it's difficult to know if the prospect of financial remuneration affected the recruitment process for study A--it's possible that parents felt pressured to participate in study A and thus decided not to enroll their child in it.
When presented with the results of this report, the respiratory therapists did not recollect feeling influenced by the financial reward associated with study A. They did recall being highly motivated to ensure the success of study A as it was part of a high-profile, multicentered trial. However, they indicated that they had felt more comfortable discussing study B with parents as it involved a ventilation strategy for which they already had experience counseling parents.
Increasingly, professional associations, granting agencies, and national governing bodies are providing guidelines for the ethical management of research funds. (10) Sponsor payments to investigators are generally deemed acceptable as payment for time spent in research activities, though past practices of giving physicians and other members of the research team finder's fees for identifying eligible patients for pharmaceutical trials (11) is now considered ethically problematic. (12) Today, many ethics review boards require investigators to disclose their fee schedules and study budgets as part of the protocol review. And at some institutions, investigators are required to disclose financial ties to the trial sponsor in the consent process and/or in the consent form. (13) This requirement was not in place at the time studies A and B were conducted.
Further questions remain as to what effect financial remuneration has on a research team's activities. There may be a point at which the amount of the financial remuneration or the manner in which it is assigned could negatively impact the ethical conduct of the researcher. On the other hand, studies answering important research questions are worth pursuing in patients' best interests, and it is important to recognize that clinical researchers deserve to be both supported and promoted in their efforts to conduct sound ethical research.
There were no sources of funding. There are no conflicts of interest to declare. The data were presented at the Pediatric Academic Societies meeting in May 2005 but have not been published in any other format.
(1.) Walson PD. Patient recruitment: U.S. perspective. Pediatrics 1999;104:619-622.
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(3.) Rao JN, Cassia LJS. Ethics of undisclosed payments to doctors recruiting patients in clinical trials. BMJ 2002;325:36-37; Shalala D. Protecting research subjects--what must be done. NEJM 2000;343:808-810; LaPuma J, Stocking CB, Rhoades WD, Darling CM. An ethical debate: Financial ties as part of informed consent to post marketing research. Attitudes of American doctors and patients. BMJ 1995;310:1660-1661.
(4.) Eichenwald K, Kolata G. Drug trials hide conflicts for doctors. New York Times, May 16, 1999.
(5.) Munro M. Bounty-hunting doctors recruit human guinea pigs: Doctors earn thousands by talking their patients into being subjects in drug trials, raising ethical and even legal questions. The Ottawa Citizen, February 23, 2004.
(6.) See ref. 3, Shalala 2000.
(7.) Burgess E, Singhal N, Amin H, et al. Consent for clinical research in the neonatal intensive care unit: A retrospective survey and a prospective study. Archives of Disease in Childhood Fetal Neonatal Edition 2003;88:F280-286.
(8.) Shields-Poe D, Pinelli J. Variables associated with parental stress in the neonatal intensive care unit. Neonatal Network 1997;16:29-37.
(9.) Rothmier JD, Lasley MV, Shapiro GG. Factors influencing parental consent in pediatric clinical research. Pediatrics 2003;111:1037-1041; Gammelgaard A, Knudsen LE, Bisgaard H. Perceptions of parents on the participation of their infants in clinical research. Archives of Disease in Childhood 2006;91:977-980.
(10.) Association of American Medical Colleges (AAMC). Task Force on Financial Conflicts of Interest in Clinical Research. Protecting Subjects, Preserving Trust, Promoting Progress--Policy and Guidelines for the Oversight of Individual Financial Interests in Human Subjects Research, December 2001; Association of American Universities (AAU). Task Force on Research Accountability. Report on Individual and Institutional Financial Conflict of Interest, October 2001; U.S. Department of Health and Human Services. Subpart F--Responsibility of Applicants for Promoting Objectivity in Research for Which PHS Funding Is Sought, 42 U.S.C. 216, 289b-1, 299c--).
(11.) Ferris LE, Naylor D. Physician remuneration in industry-sponsored clinical trials: The case for standardized clinical trial budgets. Canadian Medical Association Journal 2004;171:883-893.
(12.) CMA policy: Physicians and the Pharmaceutical Industry. 2001. http://www.umanitoba.ca/faculties/medicine/media/ CMApolicyphysiciansandindustry.pdf; American Medical Association. Opinion 6.03 Fee Splitting: Referrals to Health Care Facilities, January 2009. http://www.ama-assn.org/ama1/pub/upload/mm/Code_of_Med _Eth/opinion/opinion603.html.
(13.) Wolf, LE. IRB policies regarding finder's fees and role conflicts in recruiting research participants. IRB: Ethics & Human Research 2009;31(1):14-19.
Sharon Unger, Lesley Wylie, Shafagh Fallah, Lee Heinrich, and Karel O'Brien, "Motivated by Money? The Impact of Financial Incentive for the Research Team on Study Recruitment," IRB: Ethics & Human Research 32, no. 1 (2010): 16-19.
* Sharon Unger, MD, FRCPC, is a Staff Neonatologist, Mount Sinai Hospital and Sickkids Hospital, University of Toronto, Toronto, Ontario, Canada; Lesley Wylie, RN, MHSM, is Manager of the Neonatal Neurodevelopmental Follow-Up Program, Mount Sinai Hospital and Sickkids Hospital, Toronto, Ontario, Canada; Shafagh Fallah, PhD, is a Statistician, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada; Lee Heinrich, MD, FRCPC, is Chief of Anesthesiology, Southlake Regional Hospital, Newmarket, Ontario, Canada; and Karel O'Brien, MB, BCh, BAO, FRCPC, is a Staff Neonatologist, Mount Sinai Hospital and Sickkids Hospital, University of Toronto, Toronto, Ontario, Canada.
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