Ethics Consultation: Recruitment Problems

Reason for Consult: Difficulties Recruiting Subjects for Trial

IRIS Synopsis: The Insulin Resistance In Stroke (IRIS) Trial is a multi-center, randomized controlled trial to determine the effectiveness of pioglitazone for reducing the risk of stroke or myocardial infarction (MI) in patients with a recent ischemic stroke or transient ischemic attack (TIA) and insulin resistance. Pioglitazone is a medication that improves insulin resistance, a condition in which insulin does not work effectively because the body is resistant to its effects. Insulin resistance can lead to diabetes and is thought to cause blood vessel disease, including stroke and heart attack, in patients with and without diabetes. Pioglitazone, by treating insulin resistance, may prevent stroke and heart attack. If this trial demonstrates a benefit of pioglitazone, it will open up a completely new therapeutic option for stroke treatment and perhaps for treatment of other vascular diseases.

IRIS Current Recruitment Strategies:

UCSF: Monitor inpatient service with NV census, contact fellow on service for permission to approach the patient about participation in the IRIS. If the patient is still hospitalized, the research assistant (RA) speaks directly with the patient and then call them to follow-up with them. If the patient is already discharged, the RA sends the subject a contact letter and brochure about the IRIS trial. In this letter, the RA will include a “Do not Contact” postcard. After 14 days of the patient mailing, if the RA does not receive the “Do not Contact” post card, the RA will contact the subject to answer any questions about the trial and to discuss interest in arranging additional consent and screening visits.

Monitor NV Outpatient service by reviewing medical records of patients scheduled for clinic. The RA then contacts the treating physician directly and asks for permission to approach the subject. The RA tries to meet with the subject after the clinic visit, but if the RA is unable to do so, the RA sends the contact letter with brochure and “Do not Contact” postcard to the subject.

SFGH: On a monthly basis, get data sent from the THREDS database containing patients that may be eligible for the study. Then perform queries on the data we get sent. Contact the treating physician of potentially eligible subjects via email or mail for permission to contact the subject. If permission is granted, then the RA sends out the contact letter with brochure and postcard.

Problems on IRIS:

• The RA was not getting data from the SFGH THREDS database since August because it has been in transition with CTSI taking over. Fortunately now they are up and running again and the RA has received some data.
• Another hurdle to IRIS enrollment has been a lack of responses from PCPs when the RA sent out letters for permission to contact subjects at SFGH. Therefore, the PI submitted a modification to send emails to the treating physicians in the hopes that this would increase the responses, but it seems the response has been the same with emails.
• There have not been as many eligible participants on the UCSF in-service. A lot of SAH patients and not as many ischemic strokes, or ischemic stroke patients that are not eligible for the study.
• When eligible patients are identified, they either send in the do-not contact postcard or when the RA calls the RA does not get return calls or when the RA speaks with them they are not interested in participation.

Suggestions from the Ethics Consultant:

• Contacted other research coordinators, e.g. in vascular surgery for tips or possibility of referral of patients
• Meet with ER coordinator
• Page or call physicians if we do not hear back from the email or letter sent
• Get community physicians involved.
• Present the IRIS Trial at community centers or senior centers

Biostatistical Consultation: Answering Reviewers' Questions

Reason for Consultation: Statistical Questions About Case-Control Design

Manuscript: “Relationship between Reasons for Disciplinary Action by State Licensing Boards and Types of Unprofessional Behaviors”

Editor's Comments: The study employed a case-control design to study the association between reasons for disciplinary action by state licensing boards and types of unprofessional behaviors. The article was well written, though a couple of analytical issues should have been described with more details or clarity.

• First, in this study, each case is matched with two controls. Although Table 1 offers an overall summary of the data, a more informative univariate analysis can be presented by appropriate tests that account for the 1:2 matching structure. In addition, one or two more sentences should be added to describe the rationale of conditional logistic regression since it is not as popular as the unconditional one. I suggest a separate section be created to discuss statistical methods used in the analysis under the Methods section.
  
• Second, is there any interaction between the types of unprofessional behaviors and other covariates being adjusted (e.g. sex)? A more thorough analysis by including appropriate interaction terms and/or stratification might be helpful to enhance the understanding of the association being studied.
  
• Third, the appropriate interpretation of the results, which is also related to the limitation of the case-control design, should be more clearly conveyed. Although several odds ratio suggest an association between unprofessional behaviors and disciplinary action, it should be emphasized that the significance or impact of unprofessional behaviors at medical school on future working behaviors at the population level also depends on factors that could not be captured by a case-control design such as absolute risk and prevalence of exposure. For example, if the absolutely risk of disciplinary action for subject with/without unprofessional behaviors is 3% and 1%, respectively, then the odds ratio is around 3, suggesting an association. Nevertheless, the absolute risk is still only 3%. If the prevalence of the unprofessional behavior is low, then the problem becomes even more minor.

Suggestions from the Biostatistics Consultant:

This consult was scheduled to give advice on statistical aspects of a recent paper submission. The paper has requested.

1. A justification for the conditional logistic regression approach. I have furnished 3 references which explain that this is the desirable analysis for matched case control studies.

http://ije.oxfordjournals.org/cgi/content/abstract/9/1/89 - Pike MC, Hill AP, Smith PG. Bias and efficiency in logistic analyses of stratified case-control studies. International journal of epidemiology 1980;9(1):89-95.

http://epirev.oxfordjournals.org/cgi/reprint/16/1/33 - Thompson WD. Statistical analysis of case-control studies. Epidemiologic reviews 1994;16(1):33-50.

http://tinyurl.com/yum2pd - Breslow N. Design and analysis of case-control studies. Annual review of public health 1982;3:29-54.

2. P-values in table 1. The appropriate OR and test should be the OR for matched studies and McNermar’s test. This is covered on p. 40 of the Thompson paper. A simple way to obtain this would be to perform a conditional logistic regression with each of the predictors in Table 1 added one-at-a-time as a single factor. This would be the simplest approach since SPSS has very limited capabilities.

3. Interactions: Mary was advised to consider which would be plausible and then return for assistance in fitting and interpreting them.

4. Practical significance: Mary was advised to consider this issue seriously. If she can obtain an estimate of the % of graduates who are disciplined, then it is possible to obtain a proportion of people with the risk factor who will be disciplined. This is helpful addition.