Vaccine vs Preventitive Antiviral Research Study

• Study objectives
• How the pilot study will work
• What will you be asked to do if you participate in the study
• Benefits of participating in the study
• Risks of participating in the study
• Participation
• Confidentiality
• Investigators
• Co-ordinators
• Household Questionnaire (Coming Soon)

» Study objectives

This study is a pilot study for a larger randomized controlled trial that is planned of a larger study that is expected to be completed during the next mismatched year. The full study is intended to ask how effective seasonal prophylaxis with oseltamivir is relative to influenza vaccine in preventing influenza illness in health adults (seasonal prophylaxis means taking oseltamivir daily during the 10-14 weeks in which most influenza activity occurs. This study will also allow us to evaluate risk factors for influenza infection among healthy adults, particularly health care workers, obtain better safety data for oseltamivir before we may need to use it in the next pandemic, and practice procedures for the dispensing and follow up of seasonal prophylaxis in healthcare workers similar to those that Mount Sinai Hospital is planning to use during the next pandemic.

In the winter of 2007/8, this pilot study is intended to assess a number of important feasibility and measurement issues for the trial, including: recruitment strategies, study procedures, appropriateness of timing of serologic measurements for assessing infection, definitions of acute respiratory illness, laboratory testing for cases of acute respiratory illness, and adherence to oseltamivir in people taking the drug for several weeks.

» How the pilot study will work

The study will involve 50 individuals who:

• Are between the ages of 18 and 69 years (inclusive)
• Are residents of Ontario and do not plan to be out of the country for more than 2 consecutive weeks between December 15th and April 1st
• Are willing to be randomized to receive either oseltamivir (Tamiflu) 75mg daily during the influenza season or licensed trivalent inactivated influenza vaccine in October/November
• Do not plan on becoming pregnant during the study
• Are employed for more than 8 hours per week during the study
• Do not have an immunocompromising medical condition

» What you will be asked to do if you agree to participate

If you wish to participate in the study, you will be randomized to either receive regular vaccine or Tamiflu. If you are randomized to the vaccine group, you will get the vaccine in October or November, at the usual time. If you are randomized to the Tamiflu group, you will start taking Tamiflu once a day at the beginning of influenza season. You would keep taking the drug daily for 13 weeks; until April 30, 2008. In addition you will be asked to do the following:

• Attend the study centre 5 to 7 times. The first visit will take about 1 hour. All other study visits will take 15 to 30 minutes each. You will be given $40 per visit to cover the cost of travel and parking
• Have a single tube of blood taken at four separate time points to measure your antibody level to influenza at the beginning of the study, determine your response to the vaccine, and test whether or not you get infected with influenza even if you not get sick
• Keep a daily diary of potential vaccine or medication side effects for 3 weeks
• Contact the study once a week to report any symptoms of acute respiratory illness by web entry, email, or a two-minute telephone call
• If you develop an acute respiratory illness, have a nasopharyngeal swab done. We anticipate that about 50% of people will develop such symptoms. If you test positive for influenza you will also be offered treatment for influenza
• If you are a woman of child-bearing potential, be willing to use an approved method of contraception for the duration of the study period

» Benefits of participating in the study

If you receive Tamiflu and if the infecting influenza strain is not matched to the vaccine (something we will not know until after the study), you may be better protected against influenza than if you take vaccine alone.

There are no other direct benefits to you for participating in this study. It is hoped that your participation will help us test the study procedures for a future trial that will assess how antiviral prophylaxis may be used for protection during a pandemic.

» Risks in participating in study

A small percentage of people have reported nausea, vomiting, abdominal pain, and diarrhea when taking Tamiflu. The symptoms reported were more often associated with the first dose and were reduced if the medication was taken with food.

There have been reports in children and adolescents of abnormal behaviour (confusion, hallucinations, suicide attempts) after oseltamivir was taken to treat influenza. These are believed by most experts to be caused by the influenza rather than by the treatment and occur at a rate of about 1 per 100,000 children prescribed Tamiflu.

The only common side effect associated with influenza vaccine is pain and/or redness at the injection site. This is usually mild and rarely interferes with normally activity. The most common serious side effect of influenza vaccine is allergy which occurs in less than 1 in 10,000 people. Influenza vaccines may also be associated with an approximately 1 in 1 million risk of a neurological disorder called Guillan-Barre syndrome.

If you are randomized to the antiviral group and if you do not take your study medication regularly for the 13 weeks of the influenza season, you may be at an increased risk of influenza infection and of transmitting influenza to your patients and/or family. Thus, it is important to take your medication as directed.

There may be some discomfort and bruising at the site where blood is drawn.

» Participation

Your participation in this study is voluntary. You can choose not to participate or you may withdraw at any time without affecting your medical care.

» Confidentiality

All information obtained during the study will be held in strict confidence. You will be identified with a study number only. No names or identifying information will be used in any publication or presentations. No information identifying you will be transferred outside the investigators in this study. During the regular monitoring of your study or in the event of an audit, your medical record may be reviewed by the Mount Sinai Hospital Research Ethics Board and/or Health Canada.

» Investigators

• Dr. Allison McGeer
• Dr. Bjug Borgundvaag
• Dr. Steven Drews
• Dr. Michael Gardam
• Dr. Kevin Katz
• Dr. Jeffrey Kwong
• Dr. Joanne Langley
• Dr. Mark Loeb
• Dr. Donald Low
• Dr. Shelly McNeil
• Ms. Christine Moore
• Dr. Matthew Muller
• Dr. Janet Raboud
• Dr. Andrew Simor
• Dr. Danuta Skowronski
• Ms. Leslie Vincent

» Co-ordinators

• Ms. Brenda Coleman
• Ms. Karen Green
• Ms. Margaret McArthur