Neurourology and Urodynamics 953-62 (1990)

Recruitment Experiences in a Stress Incontinence Clinical Trial Patricia A. Burns, Thomas Nochajski, Patricia Clesse Desotelle, and Kevin Pranikoff

School of Nursing (P.A.B., P.C.D.) and Department of Uro/ogy (K.P.), Sfate University of New York, and Research Institute on Alcoholism (T.N.), Buffalo

Major dclays and subsequent altcrations in randomized controlled clinical trials have been attributcd to poor or failed recruitment. This paper presents the recruitment methods used successfully to obtain a homogenous sample of females with stress urinary incontinence. This sample was recruited to investigate the effectiveness of a behavioral treatment. Recruitment methods and their cost effectiveness are presented for the trial’s three year duration. Yields are presented as ratios of recruited/ randomized subjects. Analysis showed professional referrals to have the lowest cost/yield, while newspaper advertisement produced the highest recruitedisubject retention. As a result of this trial’s experiences recoinmendations were made for differing recruitment strategies according to sourceiyield with additional special plans for recruiting elderly, lower income, inner city, or minority subjects.

Key words: randomized clinical trial (RCT), cost effectiveness

INTRODUCTION

Many clinical trials have been severely hampered or defeated in their investi- gative capabilities as a result of poor or failed recruitment. Some of these trials have experienced major delays in the recruitment process which consequently led to decreasing the sample size, altering the entry criteria, or extending the recruitment phase [Benedict, 1979; Collins et al., 1980; Baines, 1984; Fink, 1972; Croke, 1979; Ratzen, 19811. While many clinical trial investigators have attempted to avert these consequences with elaborate recruitment protocols, often these efforts have still proven to be inadequate in obtaining an expedient appropriate sample. Randomized clinical trials have been identified by the National Institute on Aging as a priority for testing the efficacy of incontinence treatments [Consensus Conference, 1988, NIA Workshop, April, 19831, yet a paucity of literature exists which identifies recruitment

Received for publication June 5 , 1989; accepted July 11, 1989.

This work was supported by National Institute on Aging and Divibion of Nursing grant 5UOIAG05260.

Abbreviations used: MESA-Michigan Epidemiological Study on Aging.

Address reprint requests to Patricia A. Burns, Ph.D., State University of New York, 3435 Main Street, 806 Kimball Tower, Buffalo, NY 14214.

0 1990 Wiley-Liss, tnc.

54 Burns et al.

measures for a diagnosis specific (incontinence) clinical trial. Therefore, this paper is an attempt to bridge this informational gap with a recruitment protocol and its subsequent budgetary needs.

Prior to the initiation of our randomized clinical trial which tested the efficacy of a behavioral treatment for stress urinary incontinence, the difficulties of recruiting a homogenous sample with an embarrassing situation were clearly recogniaed. The major impediments in the recruitment process were identified as 1) hesitancy of females to volunteer because of the personal nature of the problem; 2) unavailability of elderly volunteers; and 3 ) lack of physician referrals to a non-medical or surgical treatment protocol. Therefore, additional study specific recruitment strategies were projected as being essential in order to successfully recruit for this clinical trial.

This paper describes the methods adopted by the clinical trial’s research team which enabled them to recruit older volunteer female subjects who were experiencing a problem which was not only socially unacceptable, but also perceived as a natural aging phenomenon. All subjects had to be 55 years or older and physically capable, as well as mentally competent. Females were recruited from a population of Western New York area residents between 55 and 85 years of age. The most recent American household surveys including the National Health and Nutrition Examination Survey follow-up (NHANES) [Harris, et al. 19861, the MESA survey in Washtenaw County [Diokno et a1 , 19861, and the established populations for Epidemiologic Studies of the Elderly (EPESE) [White et al., 19861 report the urinary incontinence prevalence rate to be at least 30%. Using this prevalence rate, we estimated the overall potential recruitment pool in our Western New York area at 41,846. Of this number 1,092 persons actually rcsponded to various recruitment efforts and entered into a three-stage screening procedure before being eligible for randomization into the trial.

MATERIALS AND METHODS Sample Size

Sampling is one of the methodological issues that Fetter et al. [1989] regard as critical for a successful clinical trial. They specify some of the issues that need consideration when determining whether to use a homogeneous or heterogenous sample. In this study, a homogeneous sample was selected Decause women with only stress or mixed incontinence were treated as opposed to women with all types of incontinence. While this may limit the generalizability of the findings, it was more feasible for itnplementation than attempting to use sampling stratification methods. This is especially true given 1) funds allocated for the research; 2) overall costs involved in attempting to recruit a wider sample; and 3 ) limited substantiation for the treatment’s erfectiveness in womcn with other types of incontinence.

Another sampling issue that Fetter et al. [1989] point out as critical for successful clinical trials is the calculation of an adequate sample size. There is a need to expose a minimum number of subjects to risk, yet it is also necessary to obtain enough subjects in order to detect significant differences when they exist [Fetter et al., 19891. Prior to initktion of the randomized clinical trial (RCT), a pilot study was conducted in order to assess the potential efficacy of the treatment, and the feasibility of the procedure, as well as for purposes of estimating effect size necessary for calculations of an optimal sample size. Following the formulas given in Friedman et al. [1984], the effect sizes were estimated for the present study [Dormer, 19841. The

Recruitment: Cost and Retention 55

pilot study’s electromyograph post-contraction sustained score was the dependent measure used as the basis for the power analyses. For a power level of .80, at an alpha level of .05, a sample size of 45 subjects per condition was calculated as necessary to detect an effect size of .54. While this is a large effect size [Cohen, 19881, the pilot study results with only 10 subjects per cell had already shown an even larger average effect size of .56.

Screening Procedures

Recruitment respondents had to progress successfully through three screening processes before being eligible for randomization into the study. l h e first screening procedure consisted of a telephone interview by the nursc coordinator. At this time, the interviewer obtained a urological symptom history and described the nature of thc clinical trial. During this interview the coordinator delved into the actual nature of their urine loss problem to determine severity. Candidates who were experiencing a minimum of three losses per week were eligible for the second screening. At this time, subjects completed an informed consent, Mini-Mental State Exam [Folstein et al., 19751, CES-D Depression Scale [Radloff, 19771, and were assessed for the etiology of their incontinence with a physical examination. Those who demonstrated urine loss upon provocative testing and were without physical limitations proceeded to the third screening. At this final screening a urodynamic evaluation was performed using a DANTEC 2100 Urodynamic System recorder where cystometry, urethral pressures, and profilometry were obtained in both supine and standing positions. Participants who met final study criteria (i.e., diagnosis of stress or mixed incontinence) were then randomized in blocks of twelve into either of two treatment groups (Kegel Exercise alone, Biofeedback & Exercise) or a control group.

Randomization

Blocked randomization was used to assign a balanced number of subjects to each group. A block of three was used to ensure an equal number of group assignments after every third subject had been admitted to the trial. The method for order of assignments was accomplished by assigning a computer generated random number between 0 and I to each subject. The assignments were ranked from lowest to highest according to the random number with the lowest ranking belonging to Group 1 (Kegel Exercises), the intermediate Group 2 (Biofeedback and Kegel), and the highest to Group 3 (Control Group).

Subject number Random number Group assignment

.52

.01

.67

.09

.98

.33

Exclusion

Figure 1 displays the percentage and rationale for ineligibility at each of three trial screenings. As can be seen, the first screening process resulted in exclusion of 67.2% (n = 700) of the 1,042 respondents, thereby allowing only 23% (n = 207) to be

56 Burns et al.

~ LIMITED MOBILITY

CONCOMITANT

FAILURE TO LOSE URINE 136sb WITH STRESS MANEUVERS

REFUSED RANDOMIZATION

Screen Ope TELEPHONE INTERVIEW

Included N = 173 Excluded N = 169 Screen Three

URODYNAMIC EVALUATION

, URGE SYMPTOMS 39 4 2 NO LOSS OF URETHRAL

INFORMATION - 23 7% CLOSURE PRESSURE CANCELLED

2 3% PHYSICAL PROBLEMS

2 7% "TIME CONSTRAINTS

10 5%

INFECTION SELF TREATMENT RINARY TRACT

RESIDUAL: 1324. ANSPORTATION 106%

Included N = 342 OTHER 50 c c URINE FLOW.: Excluded N = 7W 15 MVSEC

Included N - 135 Excluded N - 38

Fig. 1. Screening process.

excluded by the remaining procedures. The major reasons for exclusions were urine loss attributed to urgency (28.9%, n = 202) and information seekers (27.996, n = 195).

While there may have been some false positives in the first group of exclusions, a less rigorous screening process would have allowed more individuals to proceed to the second and third screening, while not guaranteeing eligibility. Furthermore, the increased additional cost in time and effort expended by the trial personnel would have created an unnecessary financial burden and hinder the progress of the clinical trial.

Approximately half of those subjects who progressed through the first screening were excluded by the second screening process. However, it should be noted that of the 169 excluded, 72 (42.7%) cancelled their appointments for various reasons. Had these individuals continued, there is a strong possibility they could have met study criteria. The remaining 97 individuals were excluded by the second screening for either minimal symptoms (27.8%, n = 47), randomization refusal (13.696, n = 23), or failure to demonstrate a urine loss with stress maneuvers, (7.1%, n = 12). Other physical problems excluded the remaining 15 subjects.

One hundred seventy-three subjects successfully met the study criteria during the physical examination (second screening), and were eligible for the final urodynamic evaluation. As a result of the stringent screening procedure, 869 subjects were excluded during prior evaluations, leaving only 38 to be eliminated during the most invasive portion of the trial, the urodynamic screening. Figure 1 again illustrates the percentages of subjects excluded during this final stage. At this stage the majority of subjects failed to demonstrate loss of urethral closure pressure (39.4%. n = 15) or cancelled their appointments (23.770, n=9) . A few presented with urinary tract infections (10.596, n = 4) or had poor detrusor function.

Recruitment: Cost and Retention 57

TABLE I. Sociodemographic Characteristics of Study Subjects (N = 135)

Response

Sociodemographics N 7c

Age (yr) 55-60 61 45.2 61-70 60 44.4 7 1-76 14 10.4

White 132 97.8 Black 3 2.2

Married 95 70.4 Not married 40 29.6

Graduate school 20 14.8 College graduate 14 10.4

High school completed 33 24.4 <High school 18 13.4

Ethnicity

Marital status

Education

Post high school 50 37.0

Income 0-$9 ,999 21 20.0 $ I O,O(N1-$19 ,999 41 34.8 920,000 -$39,9 9 9 41 30.4 $40,000 -greater 20 14.8

This controlled three-step screening process resulted in obtaining a clinical trial sample of 135 individuals, which was 13% of the total initial respondents (n = 1,042). Therefore, for every eight respondents, one subject actually met all criteria and was eligible for randomization. The uncompromising screening procedurc appeared necessary not only to obtain subjects who met study criteria but also to obtain subjects who were willing to endure the entire intervention and follow-up procedures.

RESULTS Study Subject Characteristics

The sociodemographic characteristics of the clinical trial subjects arc shown in Table I. The subjects were predominantly white and middle class (80% reported income greater than $10,000 per year), with a majority of them being married (70.4%) and having a post-high-school education (87.0%). Almost half of the sample were aged 55-60 (45.2%) with 44.4% in the 61-70 group. All overall mean age of study subjects was 62 years. Our recruitment yield was excellent in the S S - 70-year-old age range, but the representation of the 2 7 1 -year-old group was minimal. Only 10% (14) were over 70 years of age with just five subjects above the age of 75. Recruitment of elderly study participants in clinical trials has been proposed by some [Leader and Neuwirth, et al., 19781 to be difficult, whereas others had no recruitment problems [Vogt et al., 19861. Our limited recruitment of the older female could have been due to either the personal nature of the problem, the small

58 Burns et al.

. . . . * ..... --*-- 1987

JAN FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC

MONTH

Fig. 2. Frequency of initial responses by month and year.

percentage of these "old-old" elderly females dwelling in the community, or their acceptance of incontinence as part of the aging process.

The incontinence history of the clinical trial group revealed an average of 12.4 years of urine loss symptoms. This history represented a relatively lengthy time period, suggesting that the average subject was 50 years of age and menopausal when the urine loss problem began. Of thc 135 clients recruited, 73.2% reported a worsening of the problem within the last three years, which seemed to be the precipitating reason for volunteering for this clinical trial.

Time of Entry and Source of Referral

Recruitment began in March of 1985 with excellent initial response to the recruitment procedures. Figure 2 displays the monthly frequency of initial interviews for the three clinical trial years. As the line graph indicates the month of March was the best month for recruitment throughout all trial years. Another surge of inquiries occurred during the late summer and early fall for the trial years 1985 and 1986.

Newspaper Advertisements

Advertisements or editorials in the major area paper may have been the reason for increased responses in the month of March for all three trial years. These recruitment methods produced a rapid influx of respondents which represented a strain on the time and resources of the staff personnel. Figure 3 shows the percentage of individuals that responded to the various recruitment sources. As can be seen, the first news editorial (March, 1985) produced a large number of respondents and, correspondingly, a large number of entries into the study. As the bar graph depicts, in 1985 approximately 26% of the total number of respondents were the result of this recruitment strategy. However, a significant number of potential subjects were lost due to inability of the personnel to manage the overwhelming response.

Recruitment: Cost and Retention 59

I- z W

W P a

30 4 27

N = 232

21

18

15

12

9

6

3

0 NEWS NEWS NEWS

N.19

NEWS - N = 6 1

SUBURBAN PHYSICIAN

N = 313

POSTER BROCHURES OTHER 3/85 9/85 86 87 PAPERS

REFERRAL SOURCES

Fig. 3. Response to variow recruitment methods.

Newspaper advertisements in the year 1986 yielded 22% of the total respon- dents with 1987 yielding only 2% of total respondents. Over the three year trial period, approximately 50% of the total respondents were recruited as the result of advertisements or articles in the newspaper.

Poster

The second most productive recruitment mechanism was a well-planned poster campaign. The sections of the city and suburban areas were divided according to number of appropriate centershnd stores. The campaign began in the furthest areas from the center, during the spring and summer, with closer areas reserved for the late summer and fall seasons. The rationale for this strategy was to enable subjects to commute during clement weather. Posters with tear-off postage-paid reply cards were placed in drug stores, senior citizen centers, and shopping mall restrooms. Approx- imately six replies were received daily, and these potential subjects were readily screened and scheduled for appointments.

Other sources of referral for the study includcd responses to a health feature on a local television show, professional referrals. and responses to advertisements in various weekly newspapers and distribution of brochures. If the number of respon- dents from sources of referral depicted in Figure 3 are compared to the number of respondents derived from the newspaper advertisement, it can be seen that the most effective method of recruitment was the newspaper advertisement, with the least effective source being professional referrals. While a large portion of initial respondents was obtained from the poster campaign compared to the newspaper entries, the percentage of study entries was much less. However, an attractive element of the poster distribution was a steady influx of responses as shown by the relatively flat line in 1987 (see Fig. 2). This steady response rate was easily handled by the clinical trial personnel without resorting to a waiting list. As a result, the

60 Burns et al.

TABLE 11. CosVRetention of Recruitment Methods

Cost ($) Retention

Per subject Total Recruitment method Printinp Personnel" Total randomized respondents Entry ratio

Posters Newspaper Suburban papers Brochures Media presentation Doctor Other referrals Total

1,321 1,690

917 538

No charge No charge No charge

4,443

3.388 2,278

308 139 222 250 1 24

6,711

4,709 3,969 1.225

671 222 250 1 24

11,154

196 (24) 45 (87)

122 (lo) 338 (2) 28 (8) 0 (0) 3 (4)

732 (135)

313 52 1 61 29 89 I S 14

1,042

13:l 6: 1 6: I

is: I 1 1 : l

None 4: 1 8: 1

"Includes time expended to implcment the mcthod and screen the responses.

number of potential clients lost due to a lengthy time period between initial contact and screening was markedly reduced.

Recruitment Method Expenditures

The recruitment methods used in this study had varied expenses depending on the time expended by personnel and the actual cost of the method. Table I1 displays the various sources of recruitment with their respective costs.

The newspaper advertisement (total costs = $3,969) was the most efficient method with the highest retention of respondents. The media presentations and referrals, although least expensive, were less efficient. The overall study recruitment costs were $1 1,154 with an average cost of $83 per clinical trial subject. The expenses incurred as a result of the newspaper advertisement were $45 per subject randomized. Given that this method yielded the greatest number of inquiries, it appears to be a relatively inexpensive and effective strategy. Even though the poster method was approximately five times more costly ($196/subject) than the newspaper advertisement, personnel stress was greatly reduced due to the smaller but steadier subject response.

DISCUSSION

Newspaper advertisements produced the greatest number of responses and had the best respondentirandomized subject ratio (6: 1). All recruitment methods com- bined had a slightly higher ratio of 8 : l . Although the ratio for the newspaper advertisement was excellent, the fact that responses occurred within 2 to 3 days produced a time conflict for personnel responsible for screening and scheduling appointments. The inability to screen this large influx of respondents within an expedient time period resulted in a loss of approximately two hundred subjects. The major benefit of the poster campaign was the staggered rate o l response, which allowed personnel adequate time to manage potential subjects more cfficiently . Professional referrals were the least effective, a finding which supports the experi- ences of the Canadian National Breast Screening Study (CNBSS), and Coronary Primary Prevention Study (CPPT), who were forced to replan their recruitment

Recruitment: Cost and Retention 61

methods when professional referrals failed [Baines, 1984; Agras and Marshal, 1979; Agras et al., 19821.

Even though professional referrals historically prove inadequate, it was retained as a first step in this trial’s recruitment protocol. Pamphlets describing the study were sent to all area gynecologists and urologists. The purpose of this strategy was to communicate to physicians that they would remain the study subjects’ primary care provider. Upon completion of the study and to maintain rapport, a comprehensive report describing the patient’s progress was sent to each participant’s private physician.

This study’s recruitment strategies yielded an average “research volunteer” who was female Caucasian, in her early senior years, married, and of middle income status. Even though the newspaper advertisement was read by subscribers in a large metropolitan city, volunteers were mainly middle class suburbanites. This finding led the investigators to focus final recruitment efforts at the major surrounding suburban areas.

CONCLUSIONS

From this trial’s recruitment experiences, the following conclusions were made:

1. Prior to initiating a newspaper recruitment strategy, with expected high rates of responses, provisions should include a) adequate personnel for screening and scheduling and b) sufficient hours to treat or study a large number of subjects.

2. A poster campaign is appropriately initiated for recruitment when desiring a steady rate of volunteer responses.

3 . The costibenefit ratio of each recruitment method should be thoroughly analyzed and included as the first step in a clinical trial’s procedure manual.

4. An efficient data management system should be in operation well in advance of recruitment efforts, in order to record the information necessary for appointment-making, follow-up, and reporting.

5 . A well-planned screening protocol with specific guidelines for telephone interviews, assures quality as well as quantity of trial participants.

Our experience in recruiting older females was excellent in the 55 -70-year-old age group. The major problem encountcred was the inability to obtain a representative sample above 70 years of age. In a more recent pilot study conducted by the principal author the following strategies were found to be successful in attracting these “older” volunteer female participants:

1. Recruitment beginning in spring and ending in fall. 2. Transportation and provisions for the subject and companion. 3 . Monetary reimbursement. This was found to be a necessary provision when

free cholesterol and Papanicolaou testing failed to act as an incentive.

Our experiences in obtaining female participants has shown that recruitment plans should differ according to the age and socioeconomic group being sought. Special strategies should be employed when seeking eldcrly , lower income, inner city, or minority subjects.

62 Burns et al.

Recruitment is an important part of the overall effort for any major clinical trial. It constitutes a significant portion of the budget as well as personnel time. Clinical trials should continue to document their recruitment efforts to aid in establishing cost-effective and effort-conservative recruitment guidelines.

REFERENCES

Agras WS, Bradford M, Reagan H (1982): Recruitment: An introduction. Circulation 66(Suppl IV):IV-2-IV-5.

Agras WS, Marshal G (1979): Recruitment for the coronary primary prevention trial. Clin Pharmacol Ther 25:688-690.

Baines CJ (1984): Impediments to recruitment in the Canadian National Breast Screening Study: Response and Resolution. Controlled Clin Trials 5: 129-140.

Behavioral Interventions for Incontinence (1983. April): Workshop Proceedings of National Institute on Aging.

Benedict GW (1979): LRC coronary prevention trial: Baltimore. Clin Pharmacol Ther 2.5585. Cohen J (1988): “Statistical Power Analysis for the Behavioral Sciences,” Second Edition. Hillsdale, NJ:

Lawrence Erlbaum Associates, Publishing. Collins JF, Bingham SF, Weiss DG. Williford WO, Kuhn RM (1980): Some adaptive strategies for

inadequate sample acquisition in Veteran’a Administration Cooperative Clinical Trials. Controlled Clin Trials 1:436-448.

Croke G (1979): Recruitment for the National Cooperative Gallstone Study. Clin Pharmacol Ther

Diokno AC, Brock BM, Brown MB, Herzog AR (1986): Prevalence of urinary incontinence and other urological symptoms in the noninstitutionalized elderly. J Urol 136: 1022- 1025.

Donner A (1984): Approaches to sample size estimation in the design o l clinical trials-a review. Statistics in Medicine 3:199-214.

Fetter MS, Feetham SI,, D’Apolito K , Chaze B A , Fink A, Frink BB, Hougart MK. Rnshton CH (1989): Randomized clinical trials: Issues for researchers. Nurs Res 38(2): 1 17-120.

Fink R ( I 972): The impact of efforts to increase participation in repetitive screening for early breast cancer detection. Am J Public Health 62:328-336.

Folstein MF, Folstein S, McHugh PR (1975): Mini mental state: A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189-198.

Friedman LM, Furberg CD, DeMets DL (1984): “Fundamentals of Clinical Trials,” Fourth Printing. Great Road, Littleton, M.4: John Wright, PSG, Inc.

Harris T, Guralnik J , Madans J (1986): The National Health and Nutrition Survey I Follow-up: Prevalence and correlates of urinary incontinence in community dwelling elders. Presented at the 39th annual scientific meeting of the Gerontological Society of America, Chicago.

Leader MA. Neuwirth E (1978): Clinical research and the noninstitutionalized elderly: A model for subject recruitment. J Am Geriatr Soc 26:27-31.

Radloff LS (1977): The CES-D scale: A self-report depression scale for research in the general population. Appl Psycho1 Measurement 1:385.

Ratzan RM (1981): The experiment that wasn’t: A case report in clinical geriatric research. Gerontologist 2 1 (6):297-302.

Vogt TM, Ireland CC, Black D, Camel G , Hughes G (1986): Recruitment of elderly volunteers for a multicenter clinical trial: The Shep Pilot Study. Controlled Clin Trials 7.1 18-133.

White LR, Kohout F, Evans DA, Cornoni-Huntley J, Ostfeld .4M (1986): Related health problems. In: Cornoni-Huntley J , Brock DB, Ostfeld AM, Taylor JO, Wallace RB (eds): “Established Populations for Epidemiologic Studies of the Elderly: Resource Data Book.” Washington, DC: National Institute on Aging, U.S. Department of Health and Human Services.

25(5pt.2):691-694.