Model Institutional Review Board Application

Letter from the Scientific Advisor | Model IRB Application

Title: ALS Patient Care Database

A. PERSONNEL WHO WILL BE ENGAGED IN THE RESEARCH, AND THEIR QUALIFICATIONS: (Co-Investigators, Research Assistants, etc.)

B. GENERAL STATEMENT OF PROBLEM

1. Purpose: Include concise hypothesis(es) being tested by proposed research.

The central hypothesis of this research is that a voluntary North American database of outcomes for ALS patients can serve as a tool to better understand clinical practices in the care of ALS patients and the relationship between medical practices and clinical outcomes. Further, if shared, these data can serve to improve practices and outcomes in ALS.

2. Background and Significance: Provide summary of facts which led to selection of the problem. Investigator's previous work on the problem. References as appropriate.

Amyotrophic Lateral Sclerosis (ALS) is diagnosed in approximately 5,000 patients in the United States each year. ALS is invariably fatal, usually within 5 years after diagnosis. There are a number of controversies about the best approaches to care for ALS patients. However, most of these questions cannot been definitively answered because the number of ALS cases is too small in an individual neurologist's or hospital's experience. With the advent of new treatments for ALS it will be important for neurologists to evaluate the outcomes of patients on various combinations of therapy. One solution to this problem is to aggregate data from a large number of ALS clinics. This would provide a sufficient sample to study variations in outcomes, even for relatively small improvements in quality of life and/or life expectancy. Previous attempts to develop a shared data base of outcomes for ALS have failed both because of physician concerns about the confidentiality of their data and because of a lack of resources to support a large cooperative data base.

Sanofi is providing financial and logistical support for a North American database of ALS outcomes. They have asked Dr. Fred Anderson, Director of the UMMS Center for Outcomes Research, to manage the central data coordinating center for the ALS Patient Care Database.

C. DETAILED DESCRIPTION OF RESEARCH PLAN (especially as it affects the subject)

1. Inclusion/Exclusion Criteria - As appropriate, explain what steps will be taken to insure that subjects meet the criteria, e.g. healthy, not pregnant.

All patients with a diagnosis of ALS are eligible to be entered into this database. Study data forms for physicians, patients and their care givers will be available in the Neurology clinic. Exclusion criteria include patients and\or care givers who refuse to verbally consent to participate in this project and patients and\or care givers who cannot read or understand English, Spanish, or French-Canadian (the 3 languages in which the data forms are written).

2. Procedures & Methods.

a. Attach a study schema or flow diagram of the protocol as experienced by the research subjects.

1. ALS patient arrives in neurology clinic for routine appointment
2. Neurologist or nurse practitioner describes the ALS Patient Care Database project.
3. Patient eligibility confirmed.
4. Verbal consent obtained from the patient and their care giver.
5. Patient completes a questionnaire.
6. Patient's care giver is also given a questionnaire.
7. Patient is given an informational card containing the confidential ALS Clinic id number, the patient's medical record number, and Dr. _____________'s name and phone number in case there are any questions.
8. The patient and their care giver are asked to repeat the questionnaires at each clinic visit (typically at six month intervals) until death.

b. Discuss the number of subjects and controls and explain statistical basis for the numbers.

This is an observational study. This project will aggregate the data from a large number of North American ALS clinics. Confidence intervals around estimates of proportions will become very small as we accumulate an expected sample of at least 1,000 ALS cases in the first year of this study. The anticipated sample of _________ patients is between ___ and ____ patients per year (essentially all cases seen here).

c. Describe each procedure to be used and include the following information:

1) how long it requires, how often it will be done;

There are no extra procedures.

2) doses & route of administration of any drugs;

There are no experimental or extra medications.

3) will hospitalization be required for research?

No.

4) whether it would always, sometimes or never be required as part of the subject's standard care.

Not applicable.

d. Will there be any material inducements - e.g., direct payment, free hospitalization, care? YES NO X If yes, explain how much, payment schedule, and any partial payment if subject does not complete study.

3. Relationship to standard therapy.

Describe standard therapy that patient would receive if not in the research study. Explain how this research intervention deviates from or replaces generally accepted standard therapy and justify the deviation.

There will be no deviation from standard therapy.

D. DESCRIBE THE POTENTIAL BENEFITS OF THIS PROJECT

Include hoped-for benefit to society and to individual subject. The risk/benefit of the study should be addressed. If there are no direct subject benefits, this should be stated.

The large observational data set to be collected in this study will provide a unique resource for neurologists, health researchers and policy makers. In addition, individual patient data, presented in the context of national benchmarks, should help participating neurologists to improve their practices. Many patients and their care givers may benefit from this opportunity to provide feedback to their physician.

E. DESCRIBE THE POTENTIAL RISK TO SUBJECTS.

1. Are there physical risks? YES NO X

Are there psychological or social risks? YES NO X

2. Describe each risk:

a. Estimate likelihood of occurrence, severity, and duration. If generally accepted quantitative estimates are available based on previous data, these should be stated. Otherwise, qualitative estimates such as "rare", "occasionally", "frequently" may be used.

N/A

b. Explain what steps will be taken to protect against its occurrence, minimizing the harm, methods for early detection of harm, and what procedures will be followed to avoid serious injury, e.g. withdrawal from study or dose reduction.

N/A

c. Explain whether or not these risks are from a procedure performed with the intent and reasonable prospect of yielding direct health related benefit to subject.

N/A

3. Confidentiality Considerations: In the course of this research project, might information be obtained about the subject that is of a private or sensitive nature?

YES X NO

If yes, explain steps that will be taken to insure confidentiality.

Patients, care givers and physicians are each research subjects whose confidentiality is to be protected.

PATIENTS and care givers: The neurologist or a member of the neurology clinic staff will explain the study to prospective patients and to their primary care giver. If the patient gives verbal consent, a confidential identification number will be assigned. Only the patient's physician will have access to the identity of study patients and their care givers.

The patient and their primary care giver will each fill out a self-assessment questionnaire.

This same questionnaire will be administered at 3 to 6 month intervals until the patient expires or the diagnosis of ALS is ruled-out.

Questionnaires may be mailed to the patient's home or they may be completed during routine visits to the ALS/MDA Clinic depending on the patient's preference and the time and space constraints in the ALS/MDA Clinic on the day the patient is seen.

PHYSICIANS: Neurologists who wish to participate in this study will send a standard enrollment form to Dr. Anderson at UMMS, who will maintain a secure computer data base of participating ALS clinics and assign a confidential identification number to each clinic and physician. This project has been reviewed and approved by the UMMC IRB.

Neurologists will use their personal and clinic ID numbers on all data forms. Quarterly summary reports of individual physician practices will be sent to participating neurologists by Dr. Anderson. These reports will be identified only by the physician's personal and clinic ID numbers. Dr. Anderson will attach physician names to the sealed envelopes containing the quarterly confidential reports. These sealed envelopes will then be given to the Sanofi sales representative who will deliver the sealed envelope to the neurologist.

Physicians will require between 10 and 20 minutes per patient to complete physician data forms (see attached draft physician data form).

Patients or their family members will require 15 to 30 minutes to complete the patient data forms, which may be done at home prior to the MDA Clinic visit (see attached patient questionnaire).

4. Economic Considerations: In the course of this research project, might subject experience any additional expenses as a result of participation. Include both out-of-pocket costs and expenses that might be covered by medical insurance?

YES NO X

If yes, please explain and justify.

F. DESCRIBE THE SUBJECT POPULATION

1. Characteristics of subject population:

a. The subject population includes (Check as appropriate): ADULTS X CHILDREN

b. Does the study population include ALL ELIGIBLE patients admitted to this institution with the condition being studied? YES X NO NOT APPLICABLE

If you answered YES TO 1b above, you may proceed to question F4, otherwise, continue with 1c.

c. Is the subject population restricted in respect to any of the following characteristics: YES NO

1. AGE RANGE X 2. HEALTH STATUS X

3. GENDER X

4. RACIAL/ETHNIC COMPOSITION X

If you responded YES to any of the above, please include a clear rationale for this restriction.

d. Will the study population specifically include a population of subjects considered "vulnerable". Vulnerable populations are children, mentally impaired, pregnant women, prisoners, fetuses. YES NO X If yes, please explain.

2. What is the source of the subject population?

3. Explain any steps taken to insure that the subject population is representative.

4. How will subjects be recruited for the study? (Consult the HSC Guidelines for restrictions on recruitment of employees, students, and inpatients.)

As part of the routine care of patients diagnosed with ALS,neurologists and/or their clinic staff will describe the purpose of the ALS Patient Care Database to eligible patients and their care givers. If the patient gives verbal consent to participate,they will be given a standard questionnaire(see attached patient questionnaire). A note will be placed in the patient's medical record that he/she has agreed to join this project. It is further proposed that the instructions on the patient questionnaire and patient identification card will serve as a patient information sheet for this project.

If the patient's primary care giver (e.g. spouse, other relative, or friend) gives verbal consent to participate, they will be given a standard questionnaire to complete (see attached patient care giver questionnaire). Participating neurologists or an authorized clinic staff member will assign identification numbers to prospective patients. A secure log will be maintained in the Department of Neurology containing the names and study ID numbers of participating patients. No unique patient identifiers will be collected in the central ALS Patient Care Database.

This should be sufficient, since only the patient's own physician will have access to their identities. We propose that the physician's completion of our participation agreement will constitute informed consent for neurologists (see attached draft of physician participation agreement). An informational letter has also been developed for participating neurologists to give to ALS patients and to their care givers at the time of recruitment for this study (See attached sample letter).

G. METHOD FOR OBTAINING INFORMED CONSENT

1. Are you requesting a waiver of the requirement for obtaining consent? YES NO X If yes, Please justify the request: and proceed to Section VI

2. As a group, are these subjects expected to be competent to give consent for themselves? YES X NO

3. Will a signed consent form be required? YES NO X

4. Will verbal consent be obtained? YES X NO

5. Will a fact sheet be given to subjects? YES X NO

6. Does subject population include minors? YES NO X

7. If yes, will children be given an assent form to sign? YES NO

8. If not, explain how the children will be approached to assent to participation. (Consult the HSC Guidelines for information about children in research studies)

9. Identify specific individuals in the project who will obtain consent from subjects. (e.g. MDs, Research Assistants,)

10. Explain the circumstances under which consent will be obtained. (i.e. how will you insure that potential subjects have adequate time to consider their options, and that possible coercion is minimal)

See #4 above.