EAACI Food Allergy and Anaphylaxis Guidelines 1

Food Allergy HRQL Measures 2

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Short title: EAACI Food Allergy HRQL Measures Guideline 4

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Key words: adults, children, EAACI, food allergy, health-related-quality-of-life, infants 6

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8

Abbreviations: 9

AGREE II appraisal of guidelines for research & evaluation 10

BoT burden of treatment 11

CBT cognitive behavioural therapy 12

DALY disability adjusted life years 13

EAACI European Academy of Allergy and Clinical Immunology 14

FAIM food allergy independent measure 15

GRADE Grading of Recommendations, Assessment, Development and Evaluation 16

HRQL Health related quality of life 17

IM independent measures 18

MCID minimal clinical important difference 19

NNT numbers needed to treat 20

QALY quality adjusted life years 21

22

23

Words: approximately 4371 (Max. 4500) 24

25

Abstract 26

Instruments have been developed and validated for the measurement of health-related 27

quality of life in patients with food allergy. This guideline has been prepared by the European 28

Academy of Allergy and Clinical Immunology’s - EAACI Guidelines for Food Allergy and 29

Anaphylaxis Group, and builds on a systematic review of the current literature on quality of 30

life instruments for food allergy. Guidance is provided on the use of such instruments in 31

research and the current limitations of their use in clinical practice is described. Gaps in 32

current knowledge as well as areas of future interest are described. This document is 33

relevant to health care workers dealing with food allergic patients, scientists engaging in 34

food allergy research and policy makers involved in regulatory aspects concerning food 35

allergy and safety. 36

37

Background 38

In recent decades, food allergy has become an important medical condition and there is 39

evidence that the prevalence may be increasing (1). As the medical morbidity and mortality 40

associated with food allergy is limited to symptoms resulting from incidental ingestions of 41

allergenic foods, conventional, symptom-based outcome measures fail to reflect the ongoing 42

burden of this condition to patients’ well being. Thus, although health-related quality of life 43

(HRQL)(Box 1) is an important outcome measure for many diseases, it is of particular 44

importance for food allergy because there are no alternatives of sufficient sensitivity for use 45

in most clinical situations. 46

A number of studies have been undertaken in the last decade which broadly address the 47

issue of quality of life in patients suffering from food allergy (2-8). Many of these studies 48

have employed questionnaires designed to illuminate some aspect of the experience of 49

patients with food allergy using both qualitative and quantitative approaches. This guideline 50

will focus on instruments designed to measure HRQL in a quantitative and disease-specific 51

fashion, and will, in particular, draw on a systematic review of existing instruments, one of 52

seven inter-linked evidence syntheses undertaken to provide a state-of-the-art synopsis of 53

the current evidence base in this area (9). That review included a comprehensive search and 54

quality assessment of instruments with special attention to the method of validation used. 55

This guideline will examine the possible applications of these instruments and provide advice 56

to clinicians and investigators on their proper use and the interpretation of results. Current 57

limitations will also be considered and unmet needs and areas of future interest identified. 58

59

Methods 60

This Guideline was produced using relevant principles detailed in the Appraisal of Guidelines 61

for Research & Evaluation (AGREE II) approach (10). This is in essence a structured approach 62

to guideline production that is designed to ensure appropriate representation of the full 63

range of stakeholders, a careful search for and critical appraisal of the relevant literature, a 64

systematic approach to the formulation and presentation of recommendations, and steps to 65

ensure that the risk of bias is minimized at each step of the process. We provide below an 66

overview of the approach used. 67

68

Clarifying the scope and purpose of the Guideline 69

In January 2012 the scope of the intended guidelines was agreed upon, including the: target 70

allergy conditions and population, the end-user group and allowing for adequate academic, 71

professional and lay presentation during guidelines development. 72

73

Ensuring appropriate stakeholder involvement 74

Participants represented a range of European countries, and academic and clinical 75

backgrounds (including medical secondary care, primary care and nursing), and patient 76

groups. The Food Allergy HRQL Taskforce continued to work together over the ensuing 18 77

months through email discussions, teleconferences and face-to-face meetings. 78

79

Systematic review of the evidence 80

The initial full range of questions that were considered important were rationalized through 81

several rounds of iteration to agree to a single key over-arching question – namely, ‘Which 82

disease-specific, validated instruments can be employed to enable assessment of the impact 83

of, and investigations and interventions for, food allergy on HRQL?’ The answer to this was 84

then pursued through a formal systematic review of the evidence (9). 85

86

Formulating recommendations 87

The GRADE approach is a transparent, evidence-based approach to formulating 88

recommendations for interventions and diagnostic tests, but this is less suitable for use in 89

the context of recommendations on the use of which quality of life instruments to select or 90

how to use or interpret these. Therefore, following identification, critical appraisal and 91

synthesis of relevant data, members of the Taskforce developed draft consensus 92

recommendations on suitable validate instruments for use in the context of IgE-mediated 93

food allergy, and the use of these instruments and interpretation of data for: (a) clinical and 94

(b) research purposes. 95

96

Peer review 97

A draft of this guideline was externally peer-reviewed by experts from a range of 98

organizations, countries and professional backgrounds. All feedback was considered by the 99

Food Allergy HRQL Taskforce and, where appropriate, final revisions were made in the light 100

of the feedback received. We will be pleased to continue to receive feedback on this 101

guideline, which should be addressed to the corresponding author. 102

103

Identification of evidence gaps 104

The process of developing this guideline has identified a number of evidence gaps and we 105

plan in future to prioritize the questions that the Food Allergy HRQL Taskforce believes 106

should be most urgently addressed through formal consensus building techniques. We plan 107

furthermore to draft outline research briefs that funders can use to commission research on 108

these questions. 109

110

Editorial independence and managing conflict of interests 111

The production of this guideline was funded and supported by EAACI. The funders did not 112

have any influence on the guideline production process, its contents or on the decision to 113

publish. Conflicts of interest statements were completed by all members of the Taskforce 114

and these were taken into account by the Food Allergy HRQL Taskforce chair as 115

recommendations were formulated. 116

117

Review of Guideline 118

The guidelines will be reviewed in 2017 and updated accordingly. However important 119

advances will be incorporated prior to this date if required. 120

121

Results 122

The development of instruments used to measure HRQL should follow a specific 123

methodology to ensure their validity, reproducibility, responsiveness (or sensitivity) and 124

interpretability (2) (Box 1). 125

126

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Box 1. Key terms 128

Health-related quality of life (HRQL): that part of quality of life affected by disease and its 129

treatment 130

Validity ensures that only that part of quality of life is being measured which is related to 131

or driven by the disease in question. It is established by correlating measurements to one 132

or more independent measures (IM) of the disease which provide an estimation of the 133

extent and severity of patients’ food allergy. An exact correlation is not expected as the 134

HRQL instrument will not be measuring the same dimensions as the IM. 135

Reproducibility ensures that measurements taken under identical conditions are 136

equivalent, and may be assessed by test re-test analysis. It is generally assessed by asking 137

patients to complete the HRQL instrument twice, a few weeks apart, during a period 138

when the is no change expected in their HRQL (e.g. when they have not experienced any 139

food allergic reactions or received any relevant interventions). 140

Responsiveness ensures that differences or changes of potential importance are not 141

missed, and is examined by measuring differences or changes in groups where these are 142

expected. It is often assessed in patients whose HRQL is expected to change (e.g. those 143

who have experienced food allergic reactions or relevant interventions). 144

Interpretability ensures that the relevance or clinical significance of measurements is 145

apparent. This is ascertained by calculating the minimal clinical important difference 146

(MCID), or the smallest change in HRQL score associated with a significant change in a 147

global rating reported by patients. 148

All of these properties were examined in the systematic review (9) Particular emphasis was 149

given to establishment of validity, which is of fundamental importance to proper instrument 150

development. 151

Twenty studies were quality appraised in the systematic review (9) and seven disease-152

specific HRQL instruments were identified as fulfilling the criteria described above (2-7;11-153

13). These included instruments for children, adolescents, adults and parent or caregiver, 154

and were either self-reported or proxy-reported (see Table 1 below). The FAQLQ (CF, TF, AF 155

and PF) instruments have undergone the most thorough validation process, including 156

assessment of their psychometric properties. 157

These instruments are all available free of charge and several are available in multiple 158

languages. They may be downloaded from the following website: www.future FA-159

HRQLsite.EAACI.org 160

161

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Table 1. Summary of food allergy specific health related quality of life instruments 163

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170

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Abbreviation

(where

stated)

Key

references

Full name Target population

(age range in years)

Respondent

FAQLQ-­CF

3 Food Allergy Quality of Life Questionnaire Child Form

Children (8 to 12)

Children (8 to 12)

FAQLQ-­TF 4 Food Allergy Quality of Life Questionnaire Teenager Form

Adolescents (13 to 18)

Adolescents (13 to 18)

FAQL-­teen 12 Food Allergy Quality of Life Assessment Tool For Adolescents

Adolescents (13 to 18)

Adolescents (13 to 18)

You and Your Food Allergy

13 You and Your Food Allergy Adolescents (13 to 18)

Adolescents (13 to 18)

FAQLQ-­AF 5 Food Allergy Quality of Life Questionnaire Adult Form

Adults (>18)

Adults (>18)

FAQL-­PB 11 Food Allergy Quality-­of-­Life Parental Burden

Parents Parents

FAQLQ-­PF 6 Food Allergy Quality of Life Questionnaire Parent Form

Children (0 to 12)

Parents

Choosing an instrument 176

If HRQL instruments are to yield useful information in patients with food allergy, it is 177

important to choose a tool that is appropriate for the setting, diagnosis and age of the 178

patient (2, 14). FAQLQ questionnaires (Table 1) have been developed and validated for 179

patients with IgE-mediated allergies (excluding Oral Allergy/Pollen Food Syndrome) and are 180

therefore not suitable for non-IgE mediated food allergies (2-7). The food allergy-specific 181

HRQL instruments have been designed to detect clinically important differences and changes 182

in the disease-specific quality of life of patients with food allergy. As they are specific for IgE-183

mediated food allergy, they do not allow for comparison with other disorders. 184

185

The choice of food allergy-specific HRQL instrument should primarily be determined by the 186

age of the patients, as highlighted in Table 1. In young children (i.e. those ≤8 years), a parent 187

proxy questionnaire (which can be used up to the age of 12 years) is required (6-7) whereas 188

patient-administered instruments are appropriate for older children (> 8 years), adolescents 189

and adults, as they can express their own social/emotional and physical well-being (5). 190

Language may also impact on the choice of instrument, not only because of differences 191

between languages, but also because of cultural differences in various areas where the same 192

language is spoken. The FAQLQ-AF has now been validated in several European countries 193

and is available in English, French, Spanish, Italian, Polish, Greek, Dutch and Icelandic (15-16) 194

The FAQLQ-PF (6-7, 17) has been validated in French, Spanish, German, Dutch, Danish and 195

Mandarin, although only the data on the first has been published in a full length paper to 196

date. Although the FAQLQ-CF has also been translated into a number of different languages, 197

the data on validity and consistency in those languages has not yet been published. Figure 1 198

provides an algorithm guiding the appropriate use of FAQLQ and key factors to take into 199

account are listed in Box 2. 200

201

Currently, there are no tools that can be used to gain insight on the contribution of the 202

parent-child relationship on the HRQL of a food allergic child. There is some evidence that 203

comparison of patient reported HRQL to parent (proxy) reported HRQL using the FAQLQs 204

can offer some insights in this area. For example, an optional section in the FAQLQ-PF 205

evaluates the amount of stress felt my mother, father, and family as a result of food allergy 206

Self-report level of stress been found to correlate significantly with parent rated HRQL for 207

the child (18-19). A parent (proxy) reported instrument is currently being developed for 208

adolescents with food allergy which may increase our knowledge of the role that adolescent-209

parent relationships play in teenagers with food allergy. Finally, the dynamics of a family 210

with a food allergic child may also be informed by assessing the parental burden using the 211

FAQL-PB (11). 212

213

Currently, the FAQLQs have only been used in the research setting to provide quantitative 214

information on the HRQL of patients with IgE-mediated food allergy to assess the effect of 215

interventions and determine outcomes (14). If they are to be used in clinic, the question 216

arises to whether they are a valid measure of HRQL at the level of individual patients to 217

guide clinical practice. Methods to assess individual validity and patient acceptability of 218

HRQL have been used in other diseases (20-21). In essence, to be useful in clinical practice, 219

reproducibility of the HRQLQ is required to be high and sensitive enough to detect 220

differences in allergy management, and the information the instrument provides must be 221

shown to affect patient management. Although the instruments described in this guideline 222

have characteristics suggesting they may be capable of providing valid HRQL assessments at 223

the level of individual patients, more studies are required in this area. One recent study (22) 224

evaluated the effectiveness of a developmentally appropriate Cognitive Behavioural Therapy 225

(CBT) intervention specifically developed to improve HRQL for children and teenagers with 226

IgE mediated food allergy. The FAQLQ-PF, CF, and TF were used and the results showed that 227

the measures were sensitive enough to detect improvement in HRQL in individual patients 228

relative to a control group. 229

230

For patients with food allergy outside the remit of current validated FAQLQ questionnaires 231

(e.g. those with non-IgE mediated food allergy) validated, generic HRQL may be considered. 232

However, these have not been designed to detect HRQL issues specific to food allergy and so 233

are unlikely to be sensitive to small but potentially important differences or changes in food 234

allergy HRQL and will be affected by any existing comorbid disorders. 235

236

237

238

239

Figure 1: Choosing an appropriate Food Allergy HRQLQ 240

241

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244

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264

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Box 2. Summary box of factors to take into account when choosing a HRQLQ for food 266

allergy 267

type of food allergy (IgE mediated or not, food-pollen syndrome) 268

research or clinical application 269

inclusion or exclusion of effects of co-morbidities 270

patient age 271

language and cultural availability/appropriateness 272

preferred respondent: parent/caregiver as proxy, or child 273

target population/individual: parent/caregiver or child 274

275

276

277

278

279

HRQLQ

Research (Group Setting) Clinical (Individual Setting)

IgE Mediated Non-IgE

Mediated

No validated tool OAS FAQLQ

Adult Consider generic validated HRQL

instruments (not all tools validated for individiual use)

Child (0-18)

FAQLQ 13-18 years 0-12 years

>8 years

FAQLQ-PF

FAQLQ-CF

FAQLQ-TF

FAQL-teen

You and Your Allergy

< 8 years

FAQLQ-PF

Care-giver

FAQLQ-PB

Using an instrument 280

Ideally, HRQL instruments should be used in the setting (language, culture and age group) in 281

which it was developed. In practice, instruments must often negotiate differences between 282

the setting of their development and their ultimate application. It is thus often advisable to 283

include an independent measure such as the FAIM in the study in the new setting in order to 284

differentiate between negative study outcomes due to lack of changes in HRQL from those 285

due to loss of validity of the HRQL measure in the new setting. 286

287

HRQL measurements are imminently suited to determine whether interventions offer a 288

benefit increment to patients which they find meaningful. In order to demonstrate this, the 289

minimally clinical important difference (MCID) for the instrument used must be determined. 290

The MCID is the smallest increment of difference or change in HRQL score which patients 291

find clinically meaningful. Currently, none of the food allergy instruments have provided a 292

MCID. This is thus an unmet need in this area, as it will allow interventions to be assessed 293

quantitatively by permitting calculation of numbers needed to treat (NNT) resulting from the 294

intervention being studied. 295

296

Pharmaco-economic research on is mostly used to identify, measure, and compare the costs, 297

risks, and benefits of programs, services, or therapies and determine which alternative 298

produces the best health outcome for the resources invested. Validated HRQL instruments 299

for food allergy can be of value because they are able to measure the benefits of health care 300

interventions from a patient perspective and ascertain whether the benefit of a particular 301

intervention. Such measurements may be expressed as Quality (of life)-Adjusted Life Years 302

(QALYs) which captures both the HRQL lost or gained and the time to which this change 303

pertains. Such information is essential to cost-utility analysis which may be important to 304

policy makers. 305

306

307

Aside from the FAIM or similar independent measure and a global assessment, many other 308

psychometric tools may be used concomitantly to gain insight into the patient experience of 309

disease and treatment. Of these, the burden of treatment (BoT) measurement deserves 310

special mention, as it allows the evaluation of disease and treatment by asking patients to 311

weigh these entities in their overall assessment of the benefits of a particular intervention. 312

Together with HRQL, this can offer a comprehensive evaluation of the net benefits of an 313

intervention. 314

315

Gaps in the evidence and recommendations 316

The development of the above described suite of high quality food allergy-specific HRQL 317

instruments is a welcome advance in helping to assess the impact of IgE-mediated food 318

allergy on patients’ quality of life. That said, it is important to note that there remain a 319

number of important research gaps in order to have a comprehensive set of tools for use in 320

the everyday management of patients with food allergy across Europe. These are 321

summarized below. 322

323

First, the MCID of existing instruments needs to be determined. This is essential to allow for 324

calculation of NNTs for clinical care and pharmaco-economic analysis. 325

326

Second, there are at present no tools for assessing HRQL in those with non-IgE-mediated 327

food allergy or in those with oral allergy/pollen food syndrome. Given that these 328

manifestations of food allergy can have a substantial impact on the quality of life of patients 329

and carers, there is a pressing need to develop appropriate instruments. 330

331

Third, the tools available for assessing HRQL in those with IgE-mediated food allergy are still 332

only available in a fraction of the languages spoken across Europe. Given that food allergy 333

affects people throughout Europe (1), formal validational work needs to be undertaken to 334

make these instruments available across the full spectrum of relevant languages. 335

336

Fourth, it should be noted that the available instruments have primarily been developed for 337

use in research contexts. Using instruments in routine clinical contexts is potentially very 338

valuable and is hence on the policy agendas of some European countries, but this does 339

require the MCID of the instruments to be established in order to assess the impact of 340

interventions/care provision on individual (rather than groups of) patients. Furthermore, in 341

order to facilitate implementation in routine care contexts, it is important that these tools 342

are validated for use across a range of platforms – for example, completion on patient 343

portals, mobile phones, tablets, and personal computers. Given the increasing move to 344

electronic health records across Europe, electronic data capture will also facilitate seamless 345

transfer into patient records. 346

347

How best to assess HRQL in the many patients with co-existent allergic problems is another 348

related clinically important consideration. The main options are to either use an 349

accompanying generic instrument (e.g. the EuroQol) or to add in additional disease specific 350

instruments for each co-morbidity. Whilst the latter approach may be feasible in those with 351

one co-morbdity (e.g. atopic eczema/dermatitis), it is likely to prove much more challenging 352

in those with multiple co-morbdities (e.g. atopic eczema/dermatitis, allergic rhinitis and 353

asthma). 354

355

Finally, there is a need to identify relevant thresholds for costs per QALY and how these 356

might vary across Europe in order to help inform policy considerations. In this respect, it is 357

important that individual, family and societal perspectives are considered. 358

359

Based on the systematic review of HRQL instruments for IgE mediated food allergy, and the 360

identification of needs and gaps in clinical practice and research, we make the following 361

recommendations. These can be divided into general recommendations (Box 3), 362

recommendations for clinicians (Box 4) and recommendations for researchers (Box 5). 363

364

365

Box 3. General Recommendations 366

1. Only validated instruments as identified by this systematic review should be used to 367

measure HRQL in food allergic subjects. 368

2. An independent measure (e.g. FAIM) should be used simultaneously as a correlating 369

measure. 370

3. An established approach should be used when the validated questionnaires are 371

translated into other languages, e.g. back translation and validation in the local language 372

– there may be important linguistic or cultural issues that invalidate the tool in other 373

countries. 374

4. To date, the FAQLQ (AF, TF, CF and PF) and FAQL-PB instruments and the You and Your 375

Food Allergy instrument are the only tools sufficiently well-validated to be used in 376

research contexts. The appropriate questionnaire will depend on the age of the patient. 377

5. Alterations to questions in the instrument are strongly discouraged, as these may 378

compromise validity. If alterations are made, the instrument requires re-validation. 379

6. The instruments recommended in this review are specific to IgE-mediated food allergy 380

and are not suited for use in patients with non-IgE mediated disease or oral allergy 381

syndrome. Furthermore, for patients where measurement of HRQL due to comorbid 382

conditions is desireable, appropriate disease-specific and/or a generic instrument may be 383

required. 384

385

Box 4. Recommendations for Clinicians 386

387

1. To date, the use of food-allergy specific HRQL tools in clinical practice has been little 388

documented. Clinicians should be aware of this and be cautious when using HRQL 389

measurements to guide mangement decisions. 390

2. There is currently also no information on the use of HRQL measurements as a form of 391

bench-marking in food allergy. 392

393

394

Box 5. Recommendations for Research 395

396

1. Research is needed on optimum methods of administration (e.g. paper, online, phone 397

etc.), procedures (e.g. frequency) and interpretation (e.g. MCID). 398

2. Research is needed on which HRQL measures (if any) are valid at the level of individual 399

patients to guide clinical practice. 400

3. Research is needed on the efficacy of disease specific HRQL instruments in the evaluation 401

of medical and technological advances, patient satisfaction and quality of care and health 402

and regulatory policy 403

4. The inclusion of HRQL in models to explain different pathways in the development, 404

expression, and impact of chronic diseases. 405

5. Norms for age, gender, and country/culture need to be developed. 406

6. Research on the relationship between responses to both proxy and self-report HRQL 407

measures. 408

7. Research on optimum methods (clinical and statistical) for evaluating HRQL in patients 409

with co-morbid conditions. 410

8. Further work is needed to see how quality adjusted life years (QALYs) for food allergy can 411

be developed, to help inform policy. 412

413

Where next with HRQL instruments? 414

The healthcare system has traditionally focused on treating disease at point of failure, such 415

as life-saving surgery or intensive medical therapy. In the case of food allergy, this occurs 416

with accidental reactions or anaphylaxis. With healthcare professionals and governments 417

now placing more of an emphasis on prevention, a different patient management model is 418

required to assess cost-effectiveness within the continuum of care. Clinically, standardized 419

HRQL measures can enhance screening patients for burdens associated with even 420

asymptomatic periods of food allergy and can be used to monitor changes . 421

Another important issue for policy makers is how HRQL can aid policy decisions in allocating 422

healthcare resources. Efforts to link quality of life gains and optimal resource allocation has 423

proved challenging in many areas of healthcare. Decisions are often taken based on the 424

outcomes of an evaluation expressed as incremental costs per QALY gained, or disability 425

adjusted life years (DALY). Measuring HRQL in economic or monetary terms has not been 426

attempted to date in the area of food allergy. Since QALYs need to be measured against 427

some threshold (usually the monetary or consumption value of QALY gains), disease-specific, 428

meaningful estimates of the value of QALY gains in food allergy need to be developed. 429

Disease specific HRQL measures can be a key tool in such a development. 430

How best to develop an efficient and integrated method of assessment and monitoring of 431

HRQL in patients with co-existent allergic problems has been a matter of recent debate. In 432

order to retain the advantages of a disease specific instrument, the use of communications 433

technology may be an option. Unlike a paper questionnaire, electronic questionnaires can be 434

developed that consist of a subgroup of questions from a much larger collection to provide 435

personalised instruments that, for example, cater for type of allergy, multiple allergy, 436

distance from medical centre, co-morbid condition. Where appropriate, section(s) on coping, 437

anxiety, risk, reactions, and management style could also be included. A further advantage 438

of an electronic system would be the ease with which a detailed database could be 439

generated for health status of individual patients on a longitudinal basis. This would allow 440

healthcare providers to target additional input to individual patients or families experiencing 441

impaired HRQL due to particular circumstances. 442

Some questions remain that impact on the future potential value of HRQL measures in 443

allergy. Firstly, what are the correlates of HRQL in food allergy (e.g. anxiety, health beliefs, 444

risk perception, information processing, coping behaviours) and how do they impact on the 445

likelihood of adverse reactions and management? Which of these variables are causally 446

related to HRQL status, and which variables are the effect of HRQL status? Lastly, as HRQL 447

depends on subjective perception of the burden of food allergy, what are the underlying 448

neuropsychological mechanisms? These questions have particular relevance for the 449

interpretation and usefulness of HRQL measures in clinical practice. As our knowledge base 450

grows, clarity will evolve about how HRQL relates to other variables. However, it is 451

important that we design studies that help to clarify the mechanisms of effect predictors and 452

outcomes. Studies must be theory driven, well designed, multi-site, and build on previous 453

work. Models should allow for bidirectional causal pathways linking health to health related 454

quality of life (including all significant variables and their weights) . For example, if the flow 455

is bi-directional for some of the components, this has profound implications in terms of 456

interpretation and application of HRQL results.The mechanisms responsible for any 457

associations should be evaluated. Such models may be seen as a blueprint for exploration as 458

well as a summary of available evidence. 459

Since the developmental process plays an important role in shaping and determining 460

physical and psychological health and HRQL, an attempt to delineate a developmental 461

pathway is also vital. Life transitions provide a naturalistic research opportunity to 462

investigate adaptability to a diagnosis of food allergy and the link to health outcomes and 463

HRQL.The pathway should take account of sensitive transition points when the interaction of 464

biopsychosocial factors may create an increased vulnerability in terms of health and well-465

being (8,23). 466

In addition to providing a meaningful way to assess the end results of health care services, 467

including clinical and therapeutic interventions, and policy, HRQL measures can allow health 468

professionals to pinpoint the time when both parents and children may need further support 469

on issues such as diet, auto-injectors, risk management, managing anxiety, and changing 470

developmental and practical challenges. It can also help us to identify unintended impacts 471

of potential management options. The use of HRQL measures cross-culturally and across 472

countries can delineate similarities, differences, and dynamic factors. Taken together, such 473

findings, combined with research on variables related to HRQL, can provides a broader view 474

on the impact of food allergy and on outcomes. 475

476

477

Acknowledgements 478

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Authors’ contribution 481

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483

Conflicts of interest 484

485

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