5. Methods

5.1    Overview

The Global Asthma Network fieldwork tools are available from this website. Guidelines for fieldworkers can be found in section 15 and section 20. A Centre Report will be sent to PI's when they register their centre, and should be completed as fieldwork progresses. Centre data should be prepared as per the Coding and Data Transfer Section.

5.2    Registration

All centres are required to register with the GAN Global Centre http://www.globalasthmanetwork.org/surveillance/register.php. The Registration Document is to be completed by each Principal Investigator and sent to the GAN Global Centre (this can be completed on line via the website, mailed by post, or a hard copy downloaded completed, scanned and emailed to info@globalasthmanetwork.org). The Registration Document is a signed declaration that the Principal Investigator intends to carry out the study according to the Global Asthma Network protocol; it will identify further details of the study to be undertaken and provide the correct contact details of the Principal Investigator. This will enable the GAN Global Centre to update the database of collaborators and to check country and centre numbers. Investigators are also asked to declare that their centre data can be put on the Global Asthma Network website at the completion of the study and archived for public access in due course.

5.3    Collaborating centres

Collaborating centres are centres from countries around the world who wish to undertake a Global Asthma Network study. The Global Asthma Network Steering Group have defined a research centre as: a distinctive population in terms of its geography, race and/or ethnic characteristics, where Principal Investigators have agreed (by submitting a Registration Document) to follow the Global Asthma Network study protocol described in this Manual. Centres are particularly sought from regions where standardised prevalence data does not exist and ideally every country in the world would participate. Where existing data suggest regional differences in asthma rhinitis or eczema, participation of additional centres will also be encouraged. The Global Asthma Network is particularly interested in urban/rural comparisons within countries⁵¹. The sample of adolescents and children taking part should not previously have been recruited systematically for research into asthma or allergies (although individual adolescents and children may have been previously involved).

5.4    Investigators

The Registration Document and subsequent documentation will enable the GAN Global Centre to keep an accurate database of the collaborators for the Global Asthma Network. A Principal Investigator may differ from the person who actively communicates with the GAN Global Centre regarding the methodology and data and if this is the situation, we request that this is clearly communicated to the GAN Global Centre. This information is requested in the Registration Document.

5.5    Subjects

5.5.1    Selection

The 13/14 year age group (adolescents) is the compulsory component of the Global Asthma Network, however not all the questions need to be included (see section 15 for further details). The video questionnaire for the adolescents is strongly recommended. The study of the 6/7 year age group (children) is strongly recommended. Inclusion of the parent(s)/guardian(s) of both age groups (Adult Questionnaire) about their own health and the environment is also a strongly recommended component.

Please read the example Centre Report (section 20.5) before you begin planning your study. The GAN Global Centre will send you a personalised Centre Report following registration.

• The population of interest is school children and their parent(s)/guardian(s) within a given geographical area.
• The compulsory requirement is to recruit a sample of 3000 13/14 year old adolescents (this number may be reduced if a centre has less than this number but must not be less than 1000 per centre unless the centre, for example, is a whole island nation with less than 1000 adolescents). Not all the questions need to be included (see section 15 for further details).
• Strongly recommended is inclusion of the 6/7 year age group. We encourage centres to study this age group and if this age group is studied, a sample of at least 3000 children will be selected (this number may be reduced if a centre has less than this number but must not be less than 1000 per centre unless the centre, for example, is a whole island nation with less than 1000 children). Not all the questions need to be included (see section 15 for further details).
• Strongly recommended is inclusion of the parents/guardians of the adolescents and children (ADULT questionnaires). Therefore there could be up to 6000 parents for each age group. Not all the questions need to be included (see section 15 for further details).
• The sampling unit will be a school for each age group. Each school in the centre that contains the age group of interest will be allocated a number. Some centres will need to use all schools in the sampling frame to obtain the required number of participants. For those that do not need to use all schools, schools should be chosen by random selection. The method used must be documented on the Centre Report.
• Sampling of each age group, if both age groups are studied, will be separate.
• Once a school has been chosen, there are several ways of choosing the students:

-     grade/level/year where the classes with most children in the age group are selected
-     age group where only the children in the age group, regardless of grade/level/year are selected
-     and other methods, which may include elements of the above methods (you will find questions relating to this section in the sample Centre Report in section 14)

• A minimum of 10 schools (or all the schools) per centre will be needed to obtain a representative sample. If a selected school refuses participation, then the school will be replaced by another chosen at random. No eligible children will be excluded from the sample unless documented.
• If a school for disabled children (e.g. blind, intellectually handicapped) is chosen, they will be studied. It is acknowledged that there may be a disproportionate number of children of the 13/14 year age group who are unable to participate in such a school. This could be a reason for rejecting a school after it had been selected and if so, must be documented.

5.5.2    Sample size and power consideration

The sample size required to detect differences in severity of asthma is higher than that required to detect the same magnitude of differences in prevalence of asthma because severe asthma is less common. The sample size estimates are stringent because of the number of hypotheses being tested and the need to be certain of the results in such a major study. A sample size of 3000 for each age group was chosen for the ISAAC study and this sample size will be used for the Global Asthma Network. This gives the following power:

1.    Prevalence of wheezing. If the true one year prevalence of wheezing is 30% in one centre and 25% in another centre, with a sample size of 3000, the study power to detect this difference will be 99% at the 1% level of significance.
2.    Severity of wheezing. If the true one year prevalence of severe asthma is 5% in one centre and 3% in another centre with a sample size of 3000 the study power to detect this difference will be 90% at the 1% level of significance.

Table 1a

The yearly increase (decrease) in prevalence of symptoms of asthma and other allergic diseases detectable after 5 years with a power of 80% at the 5% level of significance for 3 initial levels of prevalence and four different sample sizes.

Table 1b

The yearly increase (decrease) in prevalence of symptoms of asthma and other allergic diseases detectable after 5 years with a power of 90% at the 5% level of significance for 3 initial levels of prevalence and four different sample sizes.

It is recognised that some centres may have limited resources or populations but it is nevertheless desirable for them to be included in the prevalence comparisons. This summary table (Table 2) of sample size and power considerations shows the effect of changing sample size on the power of detecting differences in the prevalence of asthma:

As sampling is done by school, while the information is gained from the school pupils, there is likely to be a cluster effect. The sample sizes given above are sufficiently large to allow good power in the presence of moderate intra-cluster correlations ⁴⁹. For example, the ISAAC New Zealand studies found the intra cluster correlations for current wheeze and severe wheeze were 0.004 and 0.004 in the 6/7 year olds which corresponds to a design effect (when N=3000) of about 1.2 for severe wheeze. For the 13/14 year olds the same figures were 0.014 and 0.007. The current wheeze design effect was therefore about 1.8 (N=3000).

5.6    Study design

5.6.1    Details of the core modules

The three one page ISAAC core questionnaires will be used⁵². The aim of compiling “core” questionnaires was to ensure that comparable information on the basic epidemiology of asthma, rhinitis and eczema was obtained from as many populations as possible. The ISAAC core questions have now been expanded for the Global Asthma Network so that questions on the management of asthma are included. Additionally the EQ developed and used in ISAAC has been expanded due to the findings from the EQ (see validation of instruments for adolescents, children and adults in section 10).

It is anticipated that individual investigators may wish to supplement the questionnaire with questions of their own, but they should ensure that the form of the questionnaire, including the flow and stemming, is unchanged. Any additional questions should come at the end of the full Global Asthma Network questionnaire. Consideration must be given to the effect extra questions may have on participation rates. If centres use additional questions, the GAN Global Centre would like a copy of these to archive.

In Sections 7-9, the questionnaires are presented. For the 13/14 year olds the written questionnaires on wheezing, rhinitis and eczema are compulsory, and it is strongly recommended that they also complete the video questionnaire. Investigators are also strongly recommended to recruit the 6/7 year olds, whose parents/guardians will be asked to complete the appropriate written questionnaires on wheezing, rhinitis and eczema for their child. The parents/guardians of both the adolescents and children (strongly recommended) will be asked to complete a questionnaire regarding their own health and the environment. The Height and weight measurements (strongly recommended) of the adolescents and children will be taken at school and recorded on the questionnaires (see protocol section 20.4). The following outline summarises this design:

Phase Three Modules	13/14 years	6/7 years
1.1 Questions on symptoms of asthma, rhinitis and eczema, management and the environment	Compulsory	Strongly recommended
1.2 Asthma video questionnaire	Strongly recommended	Not used
1.3 ADULT questionnaire for both age groups parent/guardian completion	Strongly recommended	Strongly recommended

Not all questions in Modules 1.1 & 1.3 (if used) are compulsory – see section 15 for further details.

5.6.2    Video questionnaire

Global Asthma Network centres will use the international video (AVQ 3.0) developed by the Wellington Asthma Research Group for ISAAC^1-6, which is strongly recommended. Copies of the video questionnaire and the Global Asthma Network manual are available from this website

5.6.3    Season of data collection

The date of data collection must be documented on the Centre Report and at least half of the study population should be investigated before the main pollen season of the study area.

5.7    Non-participation

A participation rate of at least 80% for adolescents and 70% for children and adults is expected. Centres that have response rates <70% for adolescents and <60% for children and adults will be excluded as it is a concern that absent children may be away from school due to symptoms of asthma, rhinitis or eczema. Therefore strenuous efforts need to be made to contact these children and their parent(s)/guardian(s) and offer the opportunity of participation in the study. In the case of the adolescents and children where consent has been refused, demographic data (age, sex, ethnic group) will be sought, if possible, from the school. For the older age group, the reasons for non-participation of students may be relatively easy to obtain and document. For example, some religious groups are not permitted to view a television, and in some circumstances, the students may complete the written core questionnaires and then depart from the room when the video is shown and therefore would not participate in this section.

In the case of the younger age group, if the initial questionnaire is not returned within one week, the information letter and questionnaire will be sent again via the school. An envelope (addressed and stamped) attached to the questionnaire may encourage participation. See the fieldworkers guide in sections 15, 16, 17 & 20.

5.8    Quality control

Particular importance is attached to the quality of the data collection and procedures, to ensure confidence in the results. A Global Asthma Network Centre Report (example section 14), will be sent to every registered centre to complete as the study progresses and returned to the GAN Global Centre at the time of submitting the data to the GAN Global Centre. This will provide a detailed account of the research methodology showing how the Global Asthma Network protocol was implemented locally. Key issues include: the geographical definition of the centre; the method for sampling schools and children; participation rates; data entry; the details regarding the method of translating the core questionnaire into other language(s) and back translation to English, if appropriate and questions regarding the video (for the adolescent group). It is very important that centres contact the GAN Global Centre if they have any difficulties understanding the Centre Report (contact address section 21).

5.9    Presentation and translation

It is important that the questionnaires are prepared in a consistent manner. The order of Yes/No responses has been defined. The layout and printing of the questionnaires will be uniformly printed. The questionnaires for the 13/14 year olds will have the video questionnaire showing on the back (when folded), or they may be presented separately, with adequate identification on each page.

Translation of questionnaires from English to other languages will be standardised, by translating the English version to the local language and back translating to English by an independent person. See section 18 ‘Guidelines for the Translations of Questionnaires’ and coding of language used on the questionnaires in section 20. It is important that these procedures are followed.