About Us: Research Ethics Board

Multi-site research conducted among a University of Ottawa affiliated institution

The CHEO REB has agreed to accept (but not require) submissions using the common application form developed by the University of Ottawa-affiliated REB’s (Council of REB’s; COREB; http://www.ohri.ca/ohreb/forms.htm ). Investigators are required to submit an application to each COREB member facility in which the research would be conducted. The investigator should first submit the protocol for ethics review to the REB responsible for the primary site of the research.

Note: The University of Ottawa-affiliated REB’s have agreed to share with one another information regarding site reviews of protocols.

Introduction:

Describe the background, including the research that is relevant to the design and conduct of the study. Preliminary human data on the drug or device must be included.
Clinical drug and Medical Device trials

Investigators can refer to the Consort statement (http://www.consort-statement.org/) for information on the necessary components of clinical trials. The International Conference on Harmonization has also produced two guidance documents that are very useful (i.e., The Good Clinical Practice: consolidated guideline from the International Conference on Harmonization (E6) & The Clinical Investigation of Medicinal Products in the Pediatric Population (E11). Both documents can be found on the general web site by using the search terms, ‘E11’ or ‘E6’ (http://www.ich.org/).

Clinical drug trials (Phase I, II, and III) must be approved by Health Canada prior to their commencement. A copy of the Health Canada ‘No Objection Letter’ (NOL) must be forwarded to the REB office prior to final approval of the protocol. Please refer to the HPFB website (http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/clini/ctdcta_ctddec-eng.php ) for further information. The board will only accept applications for clinical drug trials when a Clinical Trial Application (CTA) has already been filed with Health Canada.

For Clinical drug trials, the REB requires an investigator’s brochure or product monograph (as applicable) for clinical drug trials. The Director of Pharmacy must approve these studies prior to submission to the Board.

Clinical medical device trials must comply with the regulations set forth by the appropriate Health Canada regulations (http://www.hc-sc.gc.ca/dhp-mps/md-im/index_e.html). To apply for medical device licensure in Canada, please complete a Medical Devices Establishment Licence Application Form http://www.hc-sc.gc.ca/dhp-mps/compli-conform/licences/directives/gui_mdel-doc_aeim_20051117_tc-tm_e.html . If the device is licensed, or was licensed at the time of purchase, an authorization from Health Canada for research applications is not required under the Medical Devices Regulations. A listing of medical devices licensed in Canada can be found at www.mdall.ca .

In Canada, medical devices are categorized into four classes based on the level of risk associated with their use. Class I devices present the lowest potential risk (e.g. thermometers) and do not as a result, require investigational testing authorization. Class II, III, and IV devices present higher risks to the individual and must be reviewed by Health Canada prior to undergoing further study. If the investigational testing of a device is in conjunction with a drug in a clinical trial then the sponsor must obtain authorization for the clinical trial and authorization for the use of the investigational medical device.

Following a favourable Health Canada review of the Application for Investigational Testing of a Device, Health Canada issues an authorization to conduct research. Health Canada requires notification of REB approval for a study prior to issuing such authorization. Under these circumstances, the CHEO REB can provide to the investigator certification of conditional approval for the study if such approval is the only impediment to the Health Canada license. The final REB approval will only be issued when the CHEO REB receives the No Objection Letter from the Investigator via the sponsor.

In addition, the Chair of the CHEO Product Evaluation Committee must be notified in writing of any purchase of medical devices or equipment to be used for research purposes. The committee shares responsibility with Material Management in ensuring that the supplies used are safe and suitable for our patients as well as works to prevent product duplication and promote standardization of supplies used in the hospital.

Placebo Controlled Trials are permissible under specific circumstances. The Tri-Council Guidelines for research with human subjects and the Final Report of the National Placebo Working Committee on the Appropriate Use of Placebos in Clinical Trials in Canada (July 2004) makes the following statements about placebo versus active treatment controls.

The use of an active treatment comparator in a clinical trial of a new therapy is an appropriate study design when established effective therapy or therapies exist for the population and indication under study.
A placebo comparator is only acceptable in the following situations:
- There are no established effective therapies for the population and for the indication under study.
- Existing evidence raises substantial doubt regarding the net therapeutic benefit of available therapies,
- Patients are refractory to the available therapies by virtue of their past treatment history or known medical history,

a. The study involves adding a new investigational therapy to established effective therapies (established effective therapy + new therapy vs. established effective therapy + placebo),

b. Patients have determined that the response to the established effective therapies for their condition is unsatisfactory to them,

c. Patients have previously refused established effective therapies for their condition.

Pandemic planning

The Board had endorsed the following principles for planning in a pandemic.

Any mobilization and re-allocation of research staff should be based on the needs of human subjects.
Every effort should be made to preserve the integrity and viability of those clinical trials meeting the following criteria:
- The trial holds out the prospect of immediate (physiologic) benefit (that relates to improved disease state / morbidity etc) to the research subject, AND
- The trial involves the provision of optimal care to research subjects that would otherwise not be available off – study.
Other criteria could be added to these as required. For example, if a further rationalization of services was required, those clinical trials studying interventions to cure or alleviate illness could be retained whereas those aimed at preventing illness or improving health might be inactivated for the duration of the crisis.

During a pandemic influenza outbreak, the Board’s activities would similarly be reorganized to focus on those having an immediate impact on the welfare and safety of human subjects. Practically speaking, initial and ongoing review would be restricted to protocols meeting the above criteria. The Board would partner with any centralized REB that might be implemented by the federal or provincial governments and the federal funding agencies.

Objectives: State the objectives of the study as hypotheses.

Study design and methods:

Describe the involvement of human subjects, including study procedures. Give detailed procedures for treatment, dose adjustments, etc.
Clearly delineate standard vs. experimental aspects of the treatment provided.
Describe alternatives to experimental therapy, if any.
Describe the randomization procedure, if applicable.
Describe the types, frequency and duration of tests, admissions, outpatient visits.
Consider specifying a Data Safety Monitoring Board (DSMB) if the study involves an investigational agent & blinded design.
Define criteria for withdrawing subjects from the study.
Specify the number of participants drawn from CHEO and other centres.

Analysis of the study:

Delineate the outcomes to be measured and analyzed.

Subject selection and recruitment:

Describe the rationale for research subject selection based on age/gender/ethnicity/racial categories.

·Of note, investigators who intend to collect racial information on subjects will be asked by the Board to describe the scientific basis for doing so. Health research that includes race as a variable has been criticized for lacking rigour in conceptualization, terminology and analysis. The issues include: the stigma associated with medical research that includes race or ethnicity (e.g., Ashkenazi Jews & Tay-Sachs), the inappropriate aggregation of heterogeneous racial/ethnic groups; ethnocentric bias in defining categories (e.g., non-whites), and the use of race as an explanatory variable when the underlying constructs are variables that should & can be measured directly (e.g., SES, educational status, ethnicity).
If justified, the Board routinely recommends that the investigators consider using the categories employed by Statistics Canada, that are felt to be more appropriate to Canadian society. The Census categories are also nice because they give respondents the opportunity to describe themselves in their own terms rather than forcing choices among pre-coded categories. These can be accessed from the Statistics Canada website (under groups of people designated as visible minorities).
Describe the process for recruiting patients into this research study; physicians have a duty to manage existing and potential conflicts of interest. The College of Physicians & Surgeons of Ontario’s (CPSO) has issued guidance on the topic of recruitment of patients into clinical trials by physicians (see http://www.cpso.on.ca/policies/policies/default.aspx?ID=1540 ).
The Primary CHEO Site Investigator’s name should not be included in any advertisement for research. The College of Physicians & Surgeons of Ontario (CPSO) prohibits the use of the physician’s name in any communication offering a product or service to the public http://www.cpso.on.ca/policies/policies/default.aspx?id=1778

Strategies/procedures for recruitment (See PHIPA description on Page 39 for more information).

PHIPA (Personal Health Information Protection Act, 2004) prohibits the use of patient contact information for the purposes of recruitment into a research study without the express consent of the patient. Accordingly, information about patient eligibility cannot be released to a research team, unless members of that team would normally have access to such information in the provision of clinical care (e.g., an endocrinologist who is both an investigator and clinician studying diabetic children), or the patient has consented to such a release of information.

When the practitioner is also an investigator on the research team, the Board requires that recruitment occur at arms-length from clinical care. The Board is concerned that eligible families who are under a practitioner’s care may feel beholden to him/her and inclined to agree to the study to please then or express their appreciation for their child's care. To minimize this possibility, the Board requires that another member of the care team first approach families about the study. If required, the treating practitioner-investigator can then answer any questions raised by families who were interested in participating.

When this standard cannot be met, the Board may require additional measures to ensure that consent is entirely voluntary and uninfluenced by the patient-practitioner relationship and the potential research interests of the investigator. These decisions are made on a case-by-case basis.

1. Proposals are due (by 12:00 p.m.) on the 3rd Tuesday of every month (See submission schedule on page 5). The REB meets the first Wednesday of every month to review the submissions (See meeting schedule on page 5). In most instances, investigators of applications submitted to the full Board will be invited to attend a board meeting of the REB to discuss their project.

2. The number of protocols reviewed per month is limited to ensure thorough review of each application. Protocols are generally reviewed on a first–come first–served basis, although priority may be given to a proposal because of mitigating circumstances (e.g., the protocol offers treatment that would not be available otherwise and is considered urgent).

3. All proposals must be in English. Materials should be double-sided and pages numbered consecutively; collated in complete packages, and each document stapled individually and then black-clipped or bound by elastics in collated packages.

4. The board requires one original package with original signatures, and 18 copies of the collated package. The complete package includes: The application form, the protocol, the synopsis and the consent/assent and recruitment documents as well as the investigator’s brochure and product monograph for clinical drug trials, as appropriate.

5. The turn-around time for submissions that require review by the full Board is approximately six (6) weeks from the date of submission. Submissions that are incomplete or require modifications will delay this process.

6. Under exceptional circumstances, an executive committee of the REB can be convened to review a protocol in which the standard of full review could not be met for compassionate reasons or because of the delays involved in full Board review would seriously compromise the research. Examples of this type might include ‘natural experiments’ that merit immediate study such as the impact of a catastrophic event on the number and nature of mental health patients presenting to the ER. Urgent submissions of this type can also occur when a clinical trial protocol provides the only modality for eligible patients to access treatment and no other alternative treatment is available.

The REB Chair or his/her proxy should be consulted to determine whether or not a submission will be considered for this type of urgent review. The authorizations of the Department Head and the Division Chief as well as that of Director of Pharmacy (for clinical drug trials) are required prior to submission. Other routine authorizations required of full Board submissions can be secured after the initial submission. The Ethics Coordinator should be notified as soon as possible of an investigator’s intent to submit an urgent review request.

Room R250F, 401 Smyth Road, Ottawa, Ontario, K1H 8L1

Telephone: (613) 737-7600, ext. 3272

Guidance with respect to Sample Size Calculations
Dr. Simon Dagenais and Dr. Nick Barrowman, May 2006

What is a clinical trial?

A clinical trial is a study that measures the outcomes of human participants who receive an intervention. There are numerous elements involved when a REB is deciding whether a clinical trial is ethical. One of those considerations is whether the clinical trial is likely to result in scientifically valid data. An appropriate sample size is essential to making that determination.

What should a research protocol contain regarding sample size?

The research protocol for a clinical trial must identify the specific outcome(s) that will be used to assess the efficacy of an intervention. If several outcomes will be used, one must be identified as the primary outcome. In order to determine whether the results of a clinical trial are statistically significant and therefore have the potential to improve health care, the study must plan to enroll a sufficient number of participants. The research protocol must indicate the desired study sample size and provide a suitable justification for it.

Why are REB’s interested in sample size calculations?

Sample size calculations are inherently ethical. A clinical trial that plans to recruit too few participants may be unable to accomplish its statistical objectives, thereby jeopardizing its scientific validity. This reduces the study’s potential to benefit society, threatening the risk/benefit ratio presented to participants during the informed consent process. Conversely, a clinical trial should not expose more participants than absolutely necessary to an unproven and potentially harmful intervention.

Should I consult a statistician?

Yes. These guidelines are intended to outline requirements for the simplest of sample size calculations and will not be applicable to all studies. Investigators contemplating clinical trials are strongly encouraged to consult with a statistician regarding sample size calculations prior to submitting a proposal to the REB. When applicants do not provide a suitable justification for the proposed sample size, they will be asked to do so prior to final REB approval.

What about pilot studies?

The REB recognizes that many clinical trials being proposed are innovative and may not be able to provide all parameters needed to justify the sample size. When faced with this situation, it is generally recommended to first conduct a small pilot study. Pilot studies provide investigators with an opportunity to assess the feasibility of their study methods with a small number of participants prior to undertaking a large clinical trial. In addition, one of the objectives of a pilot study is to gather data on the outcome measure that will be used in sample size calculations for future clinical trials. If an investigator is unable to provide the REB with any credible data on which to base a sample size calculation, and they are in fact proposing to conduct a pilot study, a statement to that effect may be provided in lieu of a sample size calculation.

Steps for calculating a sample size for a clinical trial with a continuous outcome measure:

1. Specify the primary outcome and outcome measure

It is best to choose a primary outcome that is clinically relevant and for which a validated and responsive outcome measure is available. Although multiple outcomes may be collected, one must be identified as the primary outcome.

2. Identify the minimal clinical important difference (MCID) in the primary outcome measure

This is the threshold difference below which clinicians do not feel the improvement noted is important enough to change their practice. This can be established from previous studies or may have been reported when the outcome measure was validated.

3. Specify the expected variance in the outcome measure

The clinical presentation of participants will often vary over time and can be established from a pilot study, previous studies for the same intervention/indication/population, or may have been reported when the outcome measure was validated.

4. Select the desired power level

The power level varies from 0 to 1 (or 0-100%) and represents the likelihood that a study will report statistically significant results with the parameters entered into the sample size calculation.

5. Select the type-I error rate

The type-I error rate also varies from 0 to 1 (or 0-100%) and represents the likelihood that a study will report statistically significant results when no true difference exists between the groups being compared.

6. Select 1-sided or 2-sided hypothesis testing

A 1-sided sample size calculation can only report whether the intervention is statistically significantly superior to the control. A 2-sided sample size calculation can report whether the intervention is statistically significantly superior to the control, as well as whether the control is in fact superior to the intervention. Investigators should always select a 2-sided sample size calculation unless there are compelling reasons not to do so.

7. Estimate study loss to follow-up: The sample size calculation reports the final number of participants required for data analysis, not the starting number of participants enrolled. It must therefore be increased to adjust for projected study dropouts.

8. Input parameters into sample size statistical software.

Impact of individual components on sample size

Here is the impact of varying each component of the sample size calculation on the sample size:

Component	Impact
Primary outcome measure	A more responsive outcome measure decreases sample size
MCID	A larger MCID decreases sample size
Variance	A smaller variance decreases sample size
Power	A smaller power decreases sample size
Type-I error rate	A larger type-I error rate decreases sample size
Tails	A 1-tailed analysis decreases sample size
Loss to follow-up	A lower rate of loss to follow-up decreases sample size

Other comments

When a clinical trial will measure multiple outcomes that are of equal importance, investigators can provide a sample size calculation for each outcome in the research protocol. The largest sample size among these equally important outcomes can then be used for enrolment purposes.

Rather than providing the result of a sample size calculation as a single number (i.e. n=48 participants), investigators are encouraged to provide a range of numbers based on different assumptions regarding the parameters. A research protocol could provide a table or graph reporting the required sample size for a range of values for each parameter (i.e. MCID, standard deviation, power, type-I error rate, tails, loss to follow-up) if there is uncertainty requiring their estimated values.

Example

A clinical trial is designed to determine the efficacy of an analgesic compared to a placebo for post-surgical pain.

Here are the parameters reported in the research protocol for the sample size calculation:

1.     The primary outcome is pain and the outcome measure is the visual analogue scale (VAS).

2.     The MCID for post-surgical pain using the VAS is 2.0.

3.     The expected standard deviation in VAS in this population is 1.5.

4.     A 2-sided calculation is chosen since both possibilities are of clinical interest.

5.     A power of 90% is chosen.

6.     A type-I error rate of 0.01 is chosen.

7.     A loss to follow-up rate of 25% is expected.

8.     The above parameters are entered into sample size calculation software, with the result that each study group must enroll 24 participants for a total of 48 participants.

Impact of individual components on sample size

Here is the impact of varying each component of the sample size calculation on the sample size:

Component	Impact
Primary outcome measure	A more responsive outcome measure decreases sample size
MCID	A larger MCID decreases sample size
Variance	A smaller variance decreases sample size
Power level	A smaller power level decreases sample size
Significance Type-I error rate	A larger significance type-I error rate decreases sample size
Tails	A 1-tailed analysis decreases sample size
Loss to follow-up	A lower dropout rate of loss to follow-up decreases sample size

Other comments

Rather than providing the result of a sample size calculation as a single number (i.e. n=48 participants), investigators are encouraged to provide a range of numbers based on different assumptions regarding the parameters. A research protocol could provide a table or graph reporting the required sample size for a range of values for each parameter (i.e. MCID, standard deviation, power level, significance Type-I error rate, tails, loss to follow-up) if there is uncertainty requiring their estimated values.

Example

A clinical trial wants is designed to determine the efficacy of an analgesic compared to a placebo for post-surgical pain.

Here are the parameters reported in the research protocol for the sample size calculation:

1.        The primary outcome is pain and the primary outcome measure is the visual analogue scale (VAS).

2.        It is established from previous studies that the MCID for post-surgical pain using the VAS is 2.0.

3.        It is established from previous studies that the expected standard deviation in VAS in this population pain is 1.5.

4.        A 2-tailed sided calculation is chosen since both possibilities are of clinical interest.

5.        A power level of 0.9 (i.e. 90%) is chosen.

6.        A, with a significance Type-I error rate of 0.01 is chosen.

7.        A dropout loss to follow-up rate of 25% is expected.

8.        The above parameters are entered into sample size calculation software, with the result that each study group must enroll 24 participants for a total of 48 participants.

Description of the limits of confidentiality. The researcher may be asked to explain this at greater length (e.g., child abuse, self-harm) in some studies.

Your personal information will be kept strictly confidential except as required or permitted by law.

For Phase I, II, or III clinical drug trials: Representatives of the sponsoring company and/or Health Canada, as well as representatives from the CHEO Research Ethics Board have access to your child’s personal information.

For clinical drug trials funded by NIH (U.S): Representatives of the sponsoring company or government regulators such as the Food and Drug Administration (U.S.) and Health Canada as well as representatives from the CHEO Research Ethics Board have access to your child’s personal information.

Anonymity should be described in simple terms.

I will not be identified in any publication or presentation of this study. Any personal information about me that leaves the hospital will be coded so that I cannot be identified by name.

If a person’s photo is to be published in full.

Although my name will not be published, my child’s photo may be published in full. As a result, my child’s identity cannot be protected fully.

Assurances should be given that the decision to participate or not in the study will not affect the care the individual receives at CHEO.

Your decision to participate or not in this study will not affect the care you receive at CHEO.

Subjects should be informed that participation is entirely voluntary, that they are free to withdraw from the study without penalty or loss of any benefit to which they would otherwise be entitled.

You are free to withdraw from the study at any time and there will be no penalty to you or your child.

Subjects should be given any new information that might influence their decision to participate in the study (as applicable)

We will inform you of any new information that might influence your decision to continue to participate in this research project.

For biology or genetic studies, subjects should be given feedback regarding any result that may be relevant to their health or that of family members.

If the research uncovers information that might be helpful to your current or future health, the researchers will contact your doctor and discuss what these results might mean. Only the doctor will be notified and the information would be kept confidential and would not become part of your medical record. If these findings are confirmed and it is believed that they are important to your health and would point to a different way of preventing, improving or treating you or your child, your doctor would then offer to discuss these findings with you. Your doctor would first advise you of any risks and benefits of sharing this information with you. Your doctor may also recommend consultation with a genetic counsellor and/or repeat testing in a clinical (not research) laboratory if necessary. It is possible that your doctor may recommend that no additional action is necessary.

Information regarding the patient’s right to compensation should be included (as applicable).

In the event that you suffer injury as a direct result of participating in this study, normal legal rules on compensation will apply. By signing this consent form you are in no way waiving your legal rights or releasing the investigator and the sponsor from their legal and professional responsibilities.

What are the costs of taking part in this study?
You will not be charged for any test or research procedure required for this study. Taking part in this study may, however, lead to added drug-related costs to you or your insurance company. This is because your insurance company or governmental drug insurance programmes (for example, Ontario Drug Benefit Program or Trillium fund) may not fully reimburse your drug-related costs. This would occur whether or not you decide to participate in this study (you will still have to pay for the some of the drugs used in treating your child). You can ask to speak with the CHEO oncology pharmacist about these added costs. No patient will be excluded from this study based on their ability to pay for additional drug costs. Everything possible will be done to help you access reimbursement from your insurance company or other third party payer.
The process of randomization should be described (as applicable).
You will be 'randomized' into one of the study groups described below. Randomization means that you are put into a group by chance. Neither you nor your doctor can choose the group you will be in. You will have an equal (one in ?) chance of being placed in any group. The purpose of randomization is to ensure that those receiving the study medication and those receiving placebo are identical in every other respect. That way, we can know for certain that any differences that we observe between the two groups are due to the study medication and nothing else.
A lay explanation of placebo (as applicable).
A placebo is an inactive substance, which may look like medicine but contains no medicine - a "sugar pill" with no treatment value. A placebo is used in research to compare the effects of a given treatment (in this case the drug, X) against no treatment at all.
A lay explanation of clinical equipoise (as applicable).
Subjects should be advised that the risks and inconveniences of the study are believed to be equivalent across the different study arms (a clinical equipoise), e.g., ‘The purpose of this study is to compare two or more treatments. Based on our current knowledge, we do not know if any (either) of the treatments being studied are significantly better than the other(s) in terms of either effectiveness or side effects. The study would be stopped if we learned that this was not in fact, true.’
An objective and fair explanation of the benefits of participating in the research (as applicable).
It is possible that this study will help develop a new therapy for others with … (specify condition). However, the therapy being offered through this study is experimental. You cannot be certain that there will be any direct benefits to you or your child.
Any effects on fertility and possible teratogenic risks must be described in full for both males and females (as applicable).
· If there is a risk of sperm mutation then: If the drug under study presents a possible risk of sperm mutation & the directive that the subject should not father a child while on the study medication then the following statement: 'It is recommended that females and males who are sexually active, take precautions to avoid pregnancy during treatment. You must notify the physician if pregnancy occurs during the course of this study. Patients on the study should discuss these risks with sexual partners of the opposite sex. Adolescents will be given appropriate information about methods of birth control. For more information about reproductive risks you may contact the study physician.” · Teratogenic risks i.e., 'It is recommended that females and males who are sexually active, take precautions to avoid pregnancy during treatment. You must notify the physician if pregnancy occurs during the course of this study. Adolescents will be given appropriate information about methods of birth control. For more information about reproductive risks you may contact the study physician.”
An explanation of the risks of Blood Draws/Venipunctures
Blood drawing causes some pain and may cause bruising, bleeding or infections at the site of the needle stick. Care will be taken to avoid theses complications. Analgesic (numbing or pain blocking) cream can be used to decrease the pain and discomfort of blood tests.

An explanation of the possible use of blood or tissue samples should be given. Subject should be given the opportunity to consent separately to the samples being used for related research usages (as applicable).

The blood / tissue samples obtained for this study are to be used for the express purpose of the research question(s). We would like your permission to use any remaining blood/tissue obtained from you or your child to answer related research questions. ___yes ____no.

An explanation of the risks to insurability relating to genetic testing.

There is a small risk of a release of information from your research records. Health and research records have been used against patients and their families. For example, in Canada, insurance companies may deny insurance to patient's with a certain illness or those that have a genetic risk of disease. Your hospital medical records cannot, however, be released unless required or permitted by law or if you sign a release of information. The researchers of this study will protect your research records so that your name, address and phone number will be kept private.

The Chair of the Research Ethics Board and the role of the committee should be explained.

The CHEO Research Ethics Board (REB) has reviewed and approved this research project. The REB is a committee of the hospital that includes individuals from different professional backgrounds. The Board reviews all research that takes place at the hospital. Its goal is to ensure the protection of the rights and welfare of people participating in research. The Board’s work is not intended to replace a parent or child’s judgment about what decisions and choices are best for them. You may contact the Chair of the Research Ethics Board, for information regarding patient’s rights in research studies at (613) 737-7600 (3272), although this person cannot provide any health-related information about the study.

Subjects must be given an opportunity to obtain a copy of the results.

At your request, you can receive a copy of the study results at the end of the study.

In presenting the research project to staff, the following points must be included:

· Staff is being asked to complete questionnaires as part of a research project.

· The project does not involve quality assurance/improvement, and as such, participation is entirely voluntary and not work-related.

· Full anonymity is assured. The decision to participate or not will in no way be shared with others.

Phrases standardisées pour décrire certains aspects importants du consentement éclair

Description des limites de la confidentialité. On pourrait demander au chercheur d’expliquer ceci en plus grand détail (p.ex. abus contre un enfant, gestes suicidaires) pour certaines études.
Vos informations personnelles sont tenues confidentielles sauf tel que permis ou exigé par la loi. Pour les phases I, II ou III d’essais cliniques de médicaments : Des représentants de la compagnie commanditaire et(ou) Santé Canada, ainsi que des représentants du Conseil d’éthique de la recherche du CHEO ont accès à vos informations personnelles. *Pour les essais cliniques de médicaments subventionnés par le NIH (États-Unis):* Des représentants de la compagnie commanditaire ou d’organismes de réglementation, comme la Food and Drug Administration (États-Unis) et Santé Canada, ainsi que des représentants du Conseil d’éthique en recherche du CHEO ont accès à vos informations personnelles.
L’anonymat devrait être décrit en termes simples.
On ne pourra m’identifier dans aucune publication ou présentation relatives à cette étude. Toute information personnelle sera encodée de façon à conserver ma confidentialité.
Si la photo d’une personne doit être publiée en son entier.
Bien que mon nom ne sera pas publié, la photo de mon enfant pourrait être publiée en son entier. Par conséquent, l’identité de mon enfant ne peut pas être entièrement protégée.
Il faut préciser les mesures prises pour préserver les données d’étude.
Toutes les données seront gardées sous clé par les chercheurs jusqu’à la fine de l’étude; elles seront ensuite détruites.
Il faut préciser que la décision de participer à l’étude ou non n’affectera aucunement les soins reçus à l’hôpital.
Votre décision de participer ou non à cette étude n’affectera pas les soins que vous recevrez au CHEO.
Il faut informer les sujets que la participation est entièrement volontaire, qu’ils sont libres de se retirer de l’étude sans aucune pénalité ni perte d’avantages auxquels ils ont droit.
Votre participation dans cette étude est tout à fait volontaire. Vous êtes libre de vous retirez de l’étude à n’importe quel moment sans aucune pénalité pour vous ou pour votre enfant.
Il faut fournir aux sujets les nouvelles informations qui pourraient influencer leur décision de participer à l’étude.
Nous vous tiendrons informés de toute nouvelle information qui pourrait influencer sur votre décision de continuer de participer à ce projet de recherche.
Pour les études biologiques ou génétiques, le chercheur doit fournir aux sujets des informations concernant les résultats de l’étude qui pourraient être pertinents pour leur santé ou celle des membres de leur famille.
Si le chercheur découvre des informations qui pourraient vous être utiles pour soit présentement ou dans l’avenir, il contactera votre médecin. Ces renseignements ne seront pas divulgués à qui que ce soit sans votre permission. Ces renseignements ne seront pas inscrits dans votre dossier médical. Si ces résultats sont confirmés et que l’on pense qu’ils sont importants pour votre santé et indiquent une autre manière de prévenir les problèmes, d’améliorer ou de vous traiter vous ou votre enfant, votre médecin offrira de discuter de ces résultats avec vous. Votre médecin vous expliquera alors les risques et les inconvénients ainsi que les avantages de partager ces renseignements avec vous. Votre médecin pourrait aussi recommander une consultation avec un conseiller en génétique. Au besoin, il pourrait aussi vous recommander de répéter les tests dans un laboratoire clinique. Il est possible que votre médecin ne recommande aucune autre mesure.
Il faut inclure des informations concernant le droit des patients à une compensation en cas de blessure.
Si vous subissez des blessures résultant directement de votre participation à ce projet de recherche, les règles juridiques normales concernant la compensation s’appliqueront. En signant ce formulaire de consentement, vous ne renoncez aucunement à vos droits juridiques et vous ne libérez pas le chercheur et le promoteur de leurs responsabilités légales et professionnelles

Quels sont les coûts associés à la participation à cette étude?
On ne vous demandera pas de payer de frais pour les tests ou les interventions nécessaires à l’étude. Participer à cette étude pourrait cependant entraîner des frais de médicaments supplémentaires, pour vous ou votre compagnie d’assurance. C’est parce que votre compagnie d’assurance ou votre programme gouvernemental d’assurance-médicaments (comme par exemple le programme ontarien d’assurance-médicament ou le Fonds Trillium) pourrait ne pas rembourser entièrement les frais de médicaments. Ceci se produirait que vous décidiez ou non de participer à cette étude (vous devrez quand même couvrir une partie du coût des médicaments utilisés pour traiter votre enfant). Vous pouvez demander à parler au pharmacien en oncologie du CHEO concernant ces frais supplémentaires. Aucun patient ne sera exclu de cette étude pour raison d’incapacité à payer les frais supplémentaires de médicaments. Tous les efforts possibles seront faits pour vous aider à obtenir le remboursement de la part de votre compagnie d’assurance ou d’un tiers.
Explication du placebo
Un placebo est une substance inactive qui pourrait ressembler à un médicament mais qui ne contient pas de médicament (une pilule de sucre) n’ayant aucun effet sur le traitement. On utilise les placebos en recherche pour comparer les effets d’un traitement (dans ce cas, le médicament X) avec aucun traitement réel.
Selon le cas, une explication simple doit être fournie au sujet du concept 'd'équilibre clinique' (tel que décrit par B. Freedman)
Les sujets doivent savoir que les risques et inconvénients de l'étude sont considérés comme équivalents dans les différents groupes de l'étude. L'objectif de cette étude est de comparer deux traitements (ou plus). Selon les connaissances actuelles, nous ne savons pas si certains des traitements sont meilleurs que d'autres, sur le plan de l'efficacité ou des effets secondaires. L'étude serait arrêtée s'il se révélait que ce n'était pas le cas.
Explication objective et complète des avantages de la participation au projet de recherche.
Il est possible que cette étude permette de développer de nouvelles thérapies pour les autres personnes présentant … (préciser la condition). Cependant, la thérapie offerte dans le cadre de cette étude est expérimentale. On ne peut pas être certain qu’elle produira des effets directs sur vous ou votre enfant.
Tous les effets sur la fécondité et les risques tératogènes possibles doivent être décrits dans le formulaire de consentement.
Si le médicament utilisé dans le cadre de cette étude présente un risque possible de mutation des spermes : ‘Il est recommandé que les femmes et les hommes qui sont actifs sexuellement prennent les précautions nécessaires pour éviter la grossesse pendant le traitement. Vous devez informer votre médecin en cas de grossesse au cours du traitement. Les patients devraient également discuter de ces risques avec leur partenaire sexuelle. Nous fournirons aux adolescents des informations au sujet de la contraception. Pour obtenir de plus amples informations, parlez-en à votre médecin’.
Explication concernant les risques des prises de sang /ponctions veineuses
Les prises de sang peuvent causer une certaine douleur et causer des bleus, un saignement ou une infection au site de la piqûre. Toutes les précautions nécessaires seront prises pour éviter ces complications. Une crème analgésique (anesthésiante ou diminuant la douleur) peut être utilisée pour prévenir la douleur ou l’inconfort reliés aux prises de sang.

Il faut fournir une explication de l’utilisation possible du sang ou des échantillons de tissus. Il faut donner aux sujets l’occasion de consentir séparément à l’utilisation des échantillons pour des besoins reliés à la recherche.
Le sang et (ou) les échantillons de tissus obtenus pour cette étude seront utilisés pour les besoins stricts de ce sujet de recherche. Permettez--nous d’utiliser votre sang ou tissu pour répondre à des questions de recherche reliées à (préciser condition). ___oui ___non.
Explication des risques associés à l’assurabilité concernant les tests de génétique
Il y a un léger risque de fuite d’informations provenant de vos dossiers médicaux. Les dossiers de santé et de recherche ont été utilisés contre certains patients et leur famille. Par exemple, au Canada, une compagnie d’assurance pourrait refuser d’assurer un patient ayant une certaine maladie ou ceux qui courent un risque de maladie génétique. Vos dossiers médicaux hospitaliers ne peuvent cependant pas être divulgués à moins que ceci ne soit obligatoire selon la législation ou encore si vous signez un formulaire de divulgation d’informations. . Les chercheurs participant à cette étude protègeront vos dossiers de recherche pour que votre nom, votre adresse et votre numéro de téléphone restent confidentiels.
Il faut expliquer le rôle du Conseil d’éthique de la recherche et de son président.
Le comité d'éthique de la recherche à réviser et approuver ce projet de recherche. Ce comité est composé personnes venant de divers milieux professionels. Le comité étudie tous les projets de recherche effectués à l’hôpital. L’objectif est de veiller à la protection des droits et du bien-être des personnes qui y participent. Le travail du Comité ne vise pas à remplacer le jugement des parents ou de l’enfant concernant quelles décisions et quels choix sont les meilleurs pour eux. Vous pouvez contacter le président du Comité d’éthique de la recherche pour obtenir des informations concernant les droits des patients dans le cadre des projets de recherche en composant le (613) 737-7600 (3272), mais cette personne ne sera pas en mesure de fournir des informations médicales.
On doit donner aux sujets l’occasion d’obtenir une copie des résultats.
Si vous en faites la demande, vous pourrez recevoir une copie des résultats de cette étude à la fin de l’étude. .
Quand un projet de recherche implique les membres du personnel, il faut inclure les points suivants :
· On demande au personnel de remplir des questionnaires dans le cadre d’un projet de recherche. · Le projet n’a aucun aspect d’appréciation/amélioration de la qualité et donc la participation est entièrement volontaire et non-reliée au travail. · L’anonymat est entièrement respecté. La décision de participer ou non ne sera aucunement communiquée à qui que ce soit..

There is no age of consent in Ontario. If an adolescent is capable of consenting (meaning that he/she can understand the information & appreciate the relevance of the decision being made), then he/she should be asked to sign the consent form and no parental consent is required.

If the adolescent is not capable to consent, parental consent and child assent should be obtained (see guidelines below).

Unlike consent, the purpose of child assent is to secure a child’s agreement to participate in the research. Providing children with written as well as verbal information regarding research enhances their understanding and should be used. The form should include simple declarative statements that describe concretely the main features of the study procedures (e.g., what will they do to me?; Why?; Will it hurt?), and the voluntary nature of research participation (Do I have to?).

The following is a general guideline of additional considerations made across the age span:

1. Children younger than 7: A simple verbal explanation of the study should be given with reassurances that they do not have to agree if they do not want to.

2. Children between the ages of 7 & 13: Informed voluntary assent should be obtained without pressure from parents or investigators. The form may or may not include a signature and co-signature.

3. Children between the ages of 14 & 15: A consent form written at a simple level should be used. The following should be explained: Study purpose, what procedures will be done, potential benefits / risks, an invitation to ask questions, and the right to withdraw from the study. A signature should be required.

4. Children 16 years of age and older: Generally, youth 16 years of age and older sign the consent form on their own behalf.

Informed consent forms must normally be available in both English and French. This requirement is based on the importance of free and informed consent in research, and the hospital's commitment to bilingual service for families and youth.

Under limited circumstances, the REB can waive the translation requirement. In order to obtain such a waiver, the investigator must demonstrate that it is either inappropriate or impracticable to require both French and English consent forms. In other words, the investigator would need to show that the additional financial, material, human, organizational and other resources needed to carry out a study in both languages are so burdensome as to render the research unfeasible. An investigator might argue, for example, that a study cannot be responsibly conducted in one or other official language because the outcome measures have not been yet been translated and the resources needed to do so are prohibitive. An investigator might also argue the bilingual requirement should be waived because the research is being conducted in a community in which neither official language is dominant (e.g., Inuktituk).

The decision to waive the requirement for consent forms in both official languages will be sensitive to the specific nature of the study. Projects are not likely to be given a waiver if they present more than minimal risk to subjects or if they offer innovative therapies to patients that would otherwise be unavailable.

There are several options open to investigators who wish to have a document translated into French. For funded projects, translation services have been negotiated with Ms. Marguerite Cohen. The invoice for the service will be sent directly to the investigator. For unfunded projects, the request for translation should be submitted to Ms. Cohen who then will then forward it to the Regional Translation Service of Eastern Ontario. The turn around time for the Regional Translation Service is estimated to be two weeks.

Investigators must ensure that the French and English versions of the consent form are equivalent in every aspect. In order to do so, a professional translator should normally carry out the work.

Research studies requiring French translation cannot be approved until the French documentation has been submitted and approved, or confirmation provided to the REB that the documentation has been submitted for translation (a copy of the email or letter to the translator).

This policy requires that a French (or English) version of the consent form be made available within two to three months of the initial approval. However, if an investigator believes that it is impossible to meet this time line, the Board should be advised and a reasonable alternate time line proposed.

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