P Seror

T Peretti-Watel

E Aparicio

Babin

    The labour market, psychosocial outcomes and health conditions in cancer survivors: protocol for a nationwide longitudinal survey 2 and 5 years after cancer diagnosis (the VICAN survey)

The labour market, psychosocial outcomes and health conditions in cancer survivors: protocol for a nationwide longitudinal survey 2 and 5 years after cancer diagnosis (the VICAN survey)

Anne-Deborah Bouhnik, [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF] Marc-Karim Bendiane, [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF][START_REF] Ferlay | Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012[END_REF] Sebastien Cortaredona, [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF][START_REF] Ferlay | Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012[END_REF] Luis Sagaon Teyssier, 1,2,3 Dominique Rey, [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF][START_REF] Ferlay | Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012[END_REF] Cyril Berenger, [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF][START_REF] Ferlay | Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012[END_REF] Valerie Seror, [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF] Patrick Peretti-Watel, [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF][START_REF] Ferlay | Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012[END_REF]

members of the VICAN Group

To cite: Bouhnik A-D, Bendiane M-K, Cortaredona S, et al. The labour market, psychosocial outcomes and health conditions in cancer survivors: protocol for a nationwide longitudinal survey 2 and 5 years after cancer diagnosis (the VICAN survey). BMJ Open 2015;5: e005971. doi:10.1136/ bmjopen-2014-005971 ▸ Prepublication history for this paper is available online. To view these files please visit the journal online (http://dx.doi.org/10.1136/ bmjopen-2014-005971).

BACKGROUND

Over the past decades, the incidence of most cancers has increased in developed countries. [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF][START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF][START_REF] Ferlay | Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012[END_REF] At the same time, earlier diagnoses and more effective treatments have led to increased survival rates for most cancers. [START_REF] Bosetti | Cancer mortality in Europe, 2005-2009, and an overview of trends since 1980[END_REF][START_REF] Verdecchia | Survival trends in European cancer patients diagnosed from 1988 to 1999[END_REF][START_REF] Verdecchia | Recent cancer survival in Europe: a 2000-02 period analysis of EUROCARE-4 data[END_REF] As a result, the population of cancer survivors is steadily increasing. This has led to a growing number of studies on cancer survivorship and the consideration of survivorship as a major stage in the continuum of care. [START_REF] Mccabe | Looking beyond survival survivorship care is critical to the future of oncology[END_REF][START_REF] Rowland | Cancer survivorship: a new challenge in delivering quality cancer care[END_REF][START_REF] Ayanian | Enhancing research on cancer survivors[END_REF][START_REF] Grunfeld | Looking beyond survival: how are we looking at survivorship?[END_REF] These studies have shown that many survivors face psychological, physical and social challenges that may impact their daily lives and their quality of life. Cancer therapies can create long-term health problems that may become permanent, such as fatigue, 11 12 pain, 13 12 lymphoedema, [START_REF] Petrek | Lymphedema in a cohort of breast carcinoma survivors 20 years after diagnosis[END_REF] infertility, [START_REF] Agarwal | Disruption of spermatogenesis by the cancer disease process[END_REF][START_REF] Armuand | Desire for children, difficulties achieving a pregnancy, and infertility distress 3 to 7 years after cancer diagnosis[END_REF][START_REF] Trivers | Estimates of young breast cancer survivors at risk for infertility in the U[END_REF] cognitive impairment, [START_REF] Rey | Self-reported cognitive impairment after breast cancer treatment in young women from the ELIPPSE40 cohort: the long-term impact of chemotherapy[END_REF] urinary disorders [START_REF] Penson | 5-Year urinary and sexual outcomes after radical prostatectomy: results from the prostate cancer outcomes study[END_REF] and sexual dysfunction. 20 21 Cancer survivors are also at increased risk of developing a second cancer or treatment-related heart failure 22 23 years after the diagnosis of the initial cancer. Regarding the psychological effects, episodes of depression, anxiety and

Strengths and limitations of this study

▪ This longitudinal survey investigates various topics related to cancer survivorship among a large population-based national sample of 4349 adults in France. ▪ The survey combines three sources of data: patient-reported outcomes, medical records and medicoadministrative databases. ▪ The use of medicoadministrative databases to select participants from among all those initially contacted, resulted in a high number of ineligible patients and a high number of patients whose eligibility remained unknown.

distress may occur even a long time after cancer diagnosis. Furthermore, depressive symptoms are often described in cancer survivors, with prevalence as high as 40% reported in those with lung cancer. However, these patients are often underdiagnosed and undertreated. [START_REF] Alfano | Recovery issues in cancer survivorship: a new challenge for supportive care[END_REF][START_REF] Sharpe | Integrated collabourative care for comorbid major depression in patients with cancer (SMaRT Oncology-2): a multicentre randomised controlled effectiveness trial[END_REF][START_REF] Suppli | Increased risk for depression after breast cancer: a nationwide population-based cohort study of associated factors in Denmark, 1998-2011[END_REF] The epidemiological evolution resulting from medical progress in screening and treatments has prompted the need to reconsider the position of people with cancer in terms of the disease consequences, in particular at the occupational level. Indeed, the short-term and long-term consequences of cancer treatment, as well as the initial diagnosis itself, can strongly influence not only workbased opportunities in terms of access into employment and a return-to-work but also workplace activities focusing on ensuring job tenure. In addition to the physical [START_REF] Chirikos | Functional impairment and the economic consequences of female breast cancer[END_REF] and cognitive [START_REF] Schagen | Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma[END_REF] limitations that may impair the participation of cancer survivors in the labour market, the role of negative relationships with co-workers 29 30 and employers [START_REF] Paraponaris | Job tenure and self-reported workplace discrimination for cancer survivors 2 years after diagnosis: does employment legislation matter?[END_REF] is an important consideration. Remaining in employment and the prospect of a return to work have both been identified as key aspects for cancer survivors' quality of life. [START_REF] Kobayashi | Effects of socioeconomic factors and cancer survivors' worries on their quality of life (QOL) in Japan[END_REF][START_REF] Short | Responding to employment concerns of cancer survivors[END_REF][START_REF] Taskila | Cancer survivors' received and needed social support from their work place and the occupational health services[END_REF] Several studies have underlined the need for comprehensive long-term care for cancer survivors 35 36 and emphasised the lack of data on the evolution of side effects of cancer treatments over time. Despite pain being one of the symptoms that most affect patients' lives, the management of persistent pain is still often suboptimal. [START_REF] Breivik | Cancer-related pain: a pan-European survey of prevalence, treatment, and patient attitudes[END_REF] To ensure a better quality of life for patients, to organise appropriate long-term follow-up for them, and to allow them to regain their place in society, it is necessary to acquire a greater understanding of the midterm and long-term physical and psychological consequences of the disease and their social impact. It was in this context that the American Cancer Society's Studies of Cancer Survivors (SCS I-II) were initiated in 2007 in the USA. [START_REF] Smith | The rationale, design, and implementation of the American Cancer Society's studies of cancer survivors[END_REF] In Europe, similar studies have been implemented, for example, the PROFILES registry in the Netherlands in 2011. [START_REF] Van De Poll-Franse | The Patient Reported Outcomes Following Initial treatment and Long term Evaluation of Survivorship registry: scope, rationale and design of an infrastructure for the study of physical and psychosocial outcomes in cancer survivorship cohorts[END_REF] Following the recommendations of the

Objectives of the VICAN survey

The aim of the VICAN survey is to document the living conditions of adult patients with cancer 2 and 5 years after cancer diagnosis. More specifically, the objectives are: ▸ First, to study the labour market outcomes. As an increasing number of people of working age are being diagnosed with cancer, growing importance is being attached to the workplace consequences of cancer. [START_REF] Marino | Sex differences in the return-to-work process of cancer survivors 2 years after diagnosis: results from a large French population-based sample[END_REF][START_REF] Mak | Unintended consequences: the social context of cancer survivors and work[END_REF][START_REF] Joutard | Continuous-time Markov model for transitions between employment and nonemployment: the impact of a cancer diagnosis[END_REF] However, some important aspects of this issue are often neglected and need further research. [START_REF] De Boer | Cancer survivors and unemployment: a meta-analysis and meta-regression[END_REF] In particular, the effect of cancer on an individual's employability needs to be disentangled from the effects of their socioeconomic status.

Integrating variables related to work characteristics will help us to understand the true effect of living with cancer on the individual survivor's economic situation. Important individual characteristics, such as economic status and psychosocial issues, may either weaken or strengthen the effects that cancer has on job tenure and employability, and need to be documented. Furthermore, the role of medical outcomes is often missing in related research studies. By simultaneously integrating variables related to an individual's economic situation, their socioeconomic characteristics and medical data related to cancer, this survey will be able to shed some important light on the deleterious effects of cancer on working life at the individual level. The collection of data over a 5-year period after diagnosis will also allow us to describe the impact of cancer on professional trajectories and the transitions between different states in the workplace. [START_REF] Joutard | Continuous-time Markov model for transitions between employment and nonemployment: the impact of a cancer diagnosis[END_REF] ▸ Second, to determine the nature, prevalence and temporality of factors that may negatively affect or improve the quality of life and daily life of cancer survivors, and to study their evolution at 2 and 5 years after cancer diagnosis. Health-related quality of life is a key element both in the evaluation of life after cancer diagnosis and in creating a balanced life for the individual. Accordingly, understanding the factors affecting long-term quality of life remains an important research issue. 38 45 Particular attention will be given in the survey to health status (treatment follow-up, management of treatment-related side effects, comorbidities, cancer relapse or second cancer) and also to psychosocial conditions (lifestyle behaviours, perceived discrimination, family and social support). Relevant questions, for example, include: Are cancer sequelae diagnosed and treated well? What is the impact of long-term sequelae on people with cancer where the prognosis is very good? Do the changes in lifestyle behaviours impact on quality of life? What is the role of social inequalities? ▸ Third, to evaluate the physical, psychological and social needs of cancer survivors. For example, one of the questions to ask is whether patients are satisfied with the information provided on treatment side effects or on the risk of treatment-induced infertility? ▸ Fourth, to compare new data with results from a French survey performed in 2004. 31 41 43 45-49 A study 2 and 5 years after cancer diagnosis In this article, we consider that cancer survivorship begins after primary treatment. [START_REF] Hewitt | From cancer patient to cancer survivor: lost in transition[END_REF] Therefore, we chose to implement the first part of the survey in patients 2 years after cancer diagnosis, effectively in the 'recovery' phase, which follows the primary treatment phase. This choice allowed us to interview survivors who had cancer with intermediate or poor prognosis.

The second interview will occur in 2015, 5 years after cancer diagnosis, effectively at the end of the 'early monitoring phase' (2-5 years after diagnosis), which is the period where the risk of relapse and of treatment side effects is greatest.

From the point of view of labour market outcomes, the choice of a survey 2 years after cancer diagnosis was based on the specificity of the social security system in France. State legislation provides considerable protection to workers and the impact of cancer diagnosis or of other chronic diseases on employability is quite different compared with many other countries, especially those where patients are confronted with a job-lock situation, whereby they are effectively tied to the same company in order to benefit from healthcare (eg, in the USA). Indeed, in France and other countries with similar social security systems, little is known about the role played by sociodemographic, socioeconomic and clinical characteristics on the capacity of patients to retain their professional situation after diagnosis. Literature about other countries has demonstrated that the deleterious effect of cancer on professional trajectories begins to manifest itself at an early stage after diagnosis, and persists beyond the first 2 years. [START_REF] Moran | Long-term employment effects of surviving cancer[END_REF] This justifies the choice of interviewing the same individuals 2 and 5 years after diagnosis, as the information gathered may help us to understand the situation with which French cancer survivors are confronted within the labour market, and to analyse the extent to which the effects of cancer on labour market outcomes are irreversible.

This article aims to describe the design and implementation of this innovative and ambitious survey, which combines patients' self-reported data, information collected from their medical records and administrative records for healthcare use.

METHODS

Definition of target population

The survey targeted adult patients with cancer diagnosed between January and June 2010. As the active treatment phase does not usually last more than 12 months, targeted patients had experienced life after cancer for at least 1 year when first interviewed 2 years after diagnosis. People under 18 years at diagnosis were excluded from the survey for legal reasons. Those over 82 years at diagnosis were also excluded for practical reasons. Although the latter group represent 7% of cancer incidence in France, [START_REF] Belot | Cancer incidence and mortality in France over the period 1980-2005[END_REF] they would have been aged >84 at the time of first data collection, and telephone interviews with this age group can be quite difficult for several reasons: they frequently live in institutions with no personal telephone line; they are prone to refuse telephone surveys; hearing problems frequently complicate the interview. 53 54 Health insurance is compulsory in France. All those treated for cancer are registered in the Long Duration Disease File of the National Health Insurance Fund (ALD file), with a code detailing the tumour site. For practical reasons, we restricted the survey to patients registered with one of the three main Health Insurance Schemes (Caisse Nationale de l'Assurance Maladie des Travailleurs Salariés (CNAMTS) for salaried workers, Régime Social des Indépendants (RSI) for self-employed workers, Mutuelle Sociale Agricole (MSA) for farmers), which together cover more than 90% of the French population. Eligibility was restricted to French-speaking patients diagnosed with first malignant cancer and living in France for at least 2 years.

Sample stratified according to age and tumour site

As our main objective was to investigate the barriers to and drivers of patients' return to work, we overrepresented those aged <54 at diagnosis, as they were aged <56 at the time of the survey and therefore too young for retirement or early retirement schemes. Accordingly, we defined two age strata-18-52 and 53-82 at diagnosis-with a weight of 50% for each stratum.

We also restricted the survey to 12 tumour sites that accounted for 88% of global cancer incidence in France in 2012. 55 Site selection depended on four criteria: global incidence, incidence by age (in line with our two age strata above), 2-year survival rate and level of scientific interest (eg, we planned to focus on lung cancer because of recent improvements in associated survival). Selected tumour sites included cancers with good prognosis (breast, prostate and thyroid cancers, melanoma), others with intermediate prognosis (colorectal, bladder, kidney, cervical, endometrial and upper aerodigestive tract cancers, non-Hodgkin lymphoma) and one with poor prognosis (lung cancer). [START_REF] Mazeau-Woynar | Survie attendue des patients atteints de cancers en France: état des lieux[END_REF] Sampling design A simple random sampling design was applied to each of the 24 strata (2 age ranges×12 tumour sites) using the ALD file. In order to over-represent people aged <54 at diagnosis and relatively rare tumour sites, we did not opt for proportional allocation. Sample sizes were determined a priori within each stratum for a global sample size of N=6000 (see table 1). The objective was to have enough statistical power to conduct analyses separately for certain tumour sites, and to complete data collection within a reasonable period of time. Based on the experience of the survey carried out in 2004, which allowed us to use data collected for many topics, [START_REF] Corroller-Soriano | La vie deux ans après le diagnostic du cancer: une enquête en 2004 sur les conditions de vie des malades[END_REF] including employment, 31 41 43 the chosen targeted sizes per tumour site and per age range seemed a good compromise. We excluded prostate, bladder and endometrial cancers from the age stratum '18-52 at diagnosis', because these cancers have a much higher incidence among older people. Conversely, we excluded thyroid cancer from the stratum '53-82 at diagnosis', because its incidence sharply decreases after age 55. [START_REF] Belot | Cancer incidence and mortality in France over the period 1980-2005[END_REF] For each stratum, we estimated the number of contacts necessary to achieve the target size using the response rate observed for the 2004 survey. We also took into account the difference in recruitment procedures between both surveys. For example, the desired sample size for the stratum 'breast cancer/18-52 at diagnosis' was N=800 in the VICAN study. In 2004, the observed response rate for this population was 59.7%. However, in that survey, patients were recruited by telephone by physicians from the National Health Insurance Fund, and the global response rate was 53.7%. Instead, in 2012, for the first data collection of VICAN, we planned to recruit participants by postal mail (see below). Accordingly, we expected a lower response rate. A survey conducted in 2007 (among patients with diabetes [START_REF] Silva | Instauration d'une insulinothérapie dans le diabète de type 2: données épidémiologiques[END_REF] ) with the same recruitment procedure (a postal letter sent by the National Health Insurance Fund) had a response rate of 45%. We expected a similar global response rate for the first data collection of VICAN. Therefore, in 2012, for patients with breast cancer diagnosed at age 18-52, the expected response rate was 59.7%×45%/53.7%=50.1%. Consequently, 1597 patients had to be contacted to recruit 800 participants.

As we planned to recruit 6000 participants, with an expected response rate of 45%, 13 333 (6000/0.45) people registered in the ALD file should have been contacted. However, in the 2004 survey, a number of those contacted proved to be ineligible for various reasons, including inaccurate diagnosis encoded in the ALD file, and hospitalisations and deceases at the time of the survey. Taking what had happened in the 2004 survey into account, we decided to slightly increase the number of scheduled contacts. In the end, 16 429 patients were contacted.

Data collection procedure

Each selected patient received a letter inviting them to participate in the survey, sent by the National Health Insurance Fund. It did not mention the INCa or the word 'cancer', only the tumour site. For example, women with a diagnosis of breast cancer were asked to participate in a survey about their 'breast disease'. This approach was chosen because in the 2004 survey 7% of participants never used the word 'cancer' during their interview. [START_REF] Corroller-Soriano | La vie deux ans après le diagnostic du cancer: une enquête en 2004 sur les conditions de vie des malades[END_REF] The letter also mentioned that information would be collected from participants' medical and administrative records. Those who agreed to participate had to send back a signed informed consent letter. Those who did not respond were considered nonrespondents. One dunning letter was sent.

In 2012, participants were interviewed using the computer-assisted telephone interview (CATI) system. A postal questionnaire was proposed to people with lung or upper aerodigestive tract cancer, as their condition could have hampered their ability to respond orally.

Data collected 2 years after diagnosis

The CATI interview questionnaire dealt with many topics: sociodemographic background and socioeconomic status, circumstances of diagnosis, relationships with the healthcare system and health professionals, treatments received and perceived side effects. The word cancer was never mentioned. The questionnaire also included items related to perceived discrimination, social support, couple relationships, sexuality since diagnosis and fertility preservation. Lifestyle-related outcomes such as diet and physical activity, and alcohol and tobacco use were documented as well, and several validated scales evaluated quality of life, fatigue and pain. Health-related quality of life was assessed using the French version of the SF12 scale. [START_REF] Burdine | The SF-12 as a population health measure: an exploratory examination of potential for application[END_REF] Cancer-related fatigue was evaluated using the EORTC QLQ scale. [START_REF] Groenvold | Validation of the EORTC QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreement[END_REF] Pain was estimated using two validated scales: the DN4 and ID-Pain questionnaires. 60 61 Moreover, since our survey focused on the impact of cancer on employment, a large part of the questionnaire was dedicated to this topic. Participants were asked about their working life during the study period (occupational status at the time of diagnosis and changes of status over the study period) and their working conditions (type of job, work contract, work schedules and income). They were also asked about the number and duration of periods of sick leave they had taken because of cancer. In addition, they were asked about perceived difficulty at work, and any work adjustments they had made or that had been proposed to them because of the disease.

For each participant, a medical survey was conducted with the physician who initiated cancer treatment, to collect detailed information regarding tumour histology (stage, grade, size) and treatments received. We also collected information from the national SNIIR-AM database, which includes financial reimbursement data (for physicians' and other health professionals' consultations, and for prescribed drugs) as well as hospital discharge records. [START_REF] Lenormand | Le système d'information de l'assurance maladie, le SNIIRAM et les échantillons de bénéficiaires[END_REF] We also collected data measured at the residential area level to investigate spatial inequalities: socioeconomic hardship indexes 63 64 and measures of healthcare availability/accessibility (general practices, hospitals).

The patient and medical questionnaires are all available on the INCa website. 65

First data collection

The first period of data collection, 2 years after diagnosis, occurred between March and December 2012.

Telephone interviews lasted on average 40 min. Among those with lung or upper aerodigestive tract cancer who had the choice between a telephonic or postal interview, 68% asked for the latter.

Among the 16 429 patients initially contacted, 6529 returned the signed informed consent form (figure 1). Patient eligibility was evaluated using three sources: a very brief questionnaire completed by patients and returned with their consent, SNIIR-AM data and the medical survey. In this context, among the 6529 individuals who provided signed informed consent, 1653 were excluded because of non-eligibility. Similarly, among the 9900 individuals who did not return the consent form, 1750 were identified as non-eligible. Consequently, of the 8279 individuals whose eligibility or non-eligibility could be ascertained, only 58.9% were effectively eligible (55.1% and 63.6% among those aged 53-82 and aged 18-52 at diagnosis, respectively). The proportion of eligible people was markedly lower than expected, especially among those aged 53-82 at diagnosis.

The main reasons for ineligibility included inaccurate diagnosis (for 51.5% of ineligible patients: benign or second cancers, or errors in ALD file regarding the tumour site), inappropriate delay between diagnosis and survey (for 21.7% of ineligible patients: in most cases late recording in the ALD file), and patient death before the survey (for 16.4% of ineligible patients). In line with the recommendations of the American Association for Public Opinion Research, in order to compute a response rate, we assumed that the proportion of eligible people was identical among those who did not return the informed consent letter ('unknown eligibility'). [START_REF]Standard definitions: final dispositions of case codes and outcome rates for surveys[END_REF] The resulting response rates were close to our expectations (42.8% for the age stratum '18-52 at diagnosis' and 44.5% for the age stratum '53-82 at diagnosis', providing an average of 43.7%). Owing to the high proportion of ineligible people, the final sample size was only N=4349.

Table 2 details the sample according to age and tumour site. Across the age×tumour site strata, the response rate varied between 37% (for women aged 53-82 at diagnosis of endometrial cancer) and 52% (18-52×non-Hodgkin lymphoma).

With respect to the medical survey, data collection took place between March 2012 and March 2013. After several reminders by phone and letters, it was completed for 87.7% of participants. SNIIR-AM data were collected for all participants.

Weighting procedures

As we used a stratified random sampling design with non-proportional allocation (see table 1), we first computed sampling weights as reciprocals of the probabilities of selection in each stratum. Second, as we collected data from the SNIIR-AM file for all contacted patients, we had the opportunity to compare eligible respondents with eligible non-respondents.

Available information included gender, age, tumour site and socioeconomic hardship index. [START_REF] Carstairs | Deprivation and health in Scotland[END_REF] We also expected that patients' health status was correlated to participation. Accordingly, we built an indicator of cancer progression using SNIIR-AM data for every patient contacted. We considered that patients who met one of the following criteria had progressive cancer: second cancer diagnosed since 2011, treatment with chemotherapy, radiotherapy or targeted therapy in 2012, admission to a palliative care unit in 2012 and death.

The proportion of women was higher among respondents (52.8% vs 41.1% among non-respondents). Respondents were also younger on average than non-respondents (60.4 vs 64.7 years), while non-respondents lived more frequently in areas with a high level of socioeconomic hardship (table 3). Breast cancer was markedly over-represented among respondents (35.1% among respondents vs 22.4% among non-respondents), while upper aerodigestive tract and lung cancers were under-represented (overall 8.9% vs 17.2%). The proportion of individuals with progressive cancer was significantly higher among non-respondents (21.8% vs 17.4%).

As gender, age, socioeconomic hardship, tumour site and cancer progression all had a significant impact on participation, we adjusted initial weights for these five variables. The final weights were created using an iterative process (ranking ratio estimation). Thanks to the resulting weights, the marginal distribution for each of these variables was the same among all respondents (N=4349), among eligible patients (N=4876) and among patients whose eligibility status remained unknown (N=8150).

Second data collection

The National Health Insurance Fund will keep a matching file in order to propose participation to the same participants 5 years after their cancer diagnosis. This second collection of data will occur in 2015.

Planned statistical analysis Data analyses will be conducted using SPSS software (PASW Statistics 18, V.18.0.3), Stata/SE software (V.12.1) or R (V.3.0.2). Cross-sectional and longitudinal analyses will be performed. For the former, multivariate linear or logistic regressions will be used, depending on the nature of the outcomes. For longitudinal analyses, linear or logistic mixed-model regressions will be used, depending on the nature of the outcomes, to account for repeated measurements. The variety of measurements included in the survey will enable us to control for a wide range of factors. A continuous-time Markov process model will be implemented to evaluate the impact of cancer diagnosis on mobility between the different states of the labour market (eg, employment, unemployment, retirement, inactivity).

DISCUSSION

Objectives of the survey Before discussing the survey's objectives, we must highlight that we collected two kinds of data: retrospective data (eg, concerning circumstances of diagnosis and treatments received) and data related to participants' current living conditions. Analyses using retrospective data may be influenced by selection bias, as only 'survivors at 2 years' were interviewed and not everyone initially diagnosed with cancer. However, this bias was certainly limited for tumour sites associated with a very good survival rate 2 years after diagnosis.

The VICAN survey has two main objectives. First, it was designed in close cooperation with the INCa, which is the official French state agency in charge of coordinating public policy related to the fight against cancer. From this perspective, the VICAN survey will be useful for public healthcare policy evaluation and orientation, in the short to medium term. For example, in order to improve the way patients are informed of cancer diagnosis, the Cancer Plan 2009-2013 approved the generalisation of the 'Diagnostic Disclosure Procedure', 40 67 whose context and content are precisely defined. Accordingly, specific questions were introduced in the first questionnaire of the VICAN survey to assess the real world implementation of this measure. Second, VICAN was designed to encourage social sciences research on 'cancer survivorship' in the French context, as psychosocial issues dominate medical issues in this specific phase of the cancer trajectory. 10 68 Using medicoadministrative databases Thanks to the specificities of the French healthcare system, we had the opportunity to use medicoadministrative databases (ALD and SNIIR-AM files). These databases are now widely used for research purposes in many fields [START_REF] Blotiere | Perforations and haemorrhages after colonoscopy in 2010: a study based on comprehensive French health insurance data (SNIIRAM)[END_REF][START_REF] Fagot | HPV vaccination in France: uptake, costs and issues for the National Health Insurance[END_REF][START_REF] Neumann | Comparative effectiveness of rosuvastatin versus simvastatin in primary prevention among new users: a cohort study in the French national health insurance database[END_REF][START_REF] Santin | In an occupational health surveillance study, auxiliary data from administrative health and occupational databases effectively corrected for nonresponse[END_REF] and provide an effective way to contact cancer survivors. In other countries, similar samples have been created as subsamples of very large general population surveys [START_REF] Elliott | The health and well-being of cancer survivors in the UK: findings from a population-based survey[END_REF] or from cancer registries covering the whole territory, [START_REF] Smith | The rationale, design, and implementation of the American Cancer Society's studies of cancer survivors[END_REF] but such surveys/registries are not available in France. Moreover, these medicoadministrative databases allowed us to target specific populations (especially regarding tumour site and time since diagnosis) and to collect data on respondents as well as nonrespondents (in order to detect and correct for participation biases). These databases also provide detailed and reliable data regarding healthcare utilisation, unlike asking patients to self-report healthcare utilisation, which is both time-consuming and liable to recall bias. It is true, however, that many studies have shown that the effects of such biases on reported outcomes are minor. [START_REF] Friedenreich | An investigation of recall bias in the reporting of past food intake among breast cancer cases and controls[END_REF][START_REF] Friedenreich | The effect of recall bias on the association of calorie-providing nutrients and breast cancer[END_REF][START_REF] Giovannucci | Recall and selection bias in reporting past alcohol consumption among breast cancer cases[END_REF][START_REF] Vrijheid | The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk[END_REF] Despite their value, the use of medicoadministrative databases raises legal and technical issues that complicate the design of the survey. These databases also contain various kinds of inaccuracies, especially since they were not initially designed as research tools. In the VICAN survey, these limitations are illustrated by the relatively high level of ineligible patients among those who were initially contacted.

Figure 1

 1 Figure 1 Sample selection pathway (VICAN, VIe après le CANcer).

Table 1

 1 Sampling design: age at diagnosis and tumour sites strata (VICAN) Reading example: among patients aged 18-52 at diagnosis, for the nine selected tumour sites, 40.6% of patients registered in the ALD file in 2012 had breast cancer. The expected figure was much lower in the sample: 26.7% (N=800). VICAN, VIe après le CANcer.

		18-52 Years old		53-82 Years old
			Expected			Expected
	Age at diagnosis	Percentage	percentage	Expected	Percentage	percentage	Expected
	Cancer type	in ALD file	in sample	size	in ALD file	in sample	size
	Breast cancer	40.6	26.7	800	17.1	16.7	500
	Prostate cancer	-	-	-	39.2	20.0	600
	Melanoma	7.3	10.0	300	2.1	5.0	150
	Thyroid cancer	9.7	10.0	300	-	-	-
	Colorectal cancer	8.7	11.7	350	14.2	10.0	300
	Upper aerodigestive tract	9.8	10.0	300	4.6	6.7	200
	cancers
	Bladder cancer	-	-	-	3.7	6.7	200
	Kidney cancer	3.2	5.0	150	3.1	5.0	150
	Non-Hodgkin lymphoma	5.3	6.7	200	3.5	6.7	200
	Cervical cancer	4.3	6.7	200	2.5	6.7	200
	Endometrial cancer	-	-	-	0.5	3.3	100
	Lung cancer	11.1	13.3	400	9.5	13.3	400
	Total	100	100	3000	100	100	3000

Table 2

 2 Final sample: age at diagnosis and tumour sites strata (VICAN)

		Age at
		diagnosis
	Cancer type	18-52 53-82 Total
	Breast cancer	971	379	1350
	Prostate cancer	-	479	479
	Melanoma	162	114	276
	Thyroid cancer	181	-	181
	Colorectal cancer	258	229	487
	Upper aerodigestive tract cancers	153	131	284
	Bladder cancer	-	143	143
	Kidney cancer	108	110	218
	Non-Hodgkin lymphoma	163	122	285
	Cervical cancer	97	78	175
	Endometrial cancer	-	75	75
	Lung cancer	136	260	396
	Total	2241	2108	4349

VICAN, VIe après le CANcer.

Table 3

 3 Comparison between eligible respondents and eligible non-respondents (VICAN)

		Respondents	Non-respondents
		(N=4349)	(N=527)
		Per cent column
	Gender
	Men	47.2	58.9
	Women	52.8	41.1***
	Age: mean (SE)	60.4 (11.4)	64.7 (11.5)***
	Social deprivation index
	<1st quartile	20.3	14.4
	(1st-3rd quartiles)	33.4	29.1
	>3rd quartile	46.3	56.5***
	Cancer type
	Breast cancer	35.1	22.4
	Prostate cancer	24.8	29.6
	Melanoma	3.1	3.1
	Thyroid cancer	2.0	1.4
	Colorectal cancer	11.8	13.3
	Upper	4.0	9.1
	aerodigestive tract
	cancers
	Bladder cancer	4.5	4.8
	Kidney cancer	3.4	3.6
	Non-Hodgkin	3.2	2.9
	lymphoma
	Cervical cancer	1.3	0.9
	Endometrial cancer	1.8	0.8
	Lung cancer	4.9	8.1***
	Cancer progression since diagnosis
	No	82.6	78.2
	Yes	17.4	21.8***

*p<0.05, **p<0.01, ***p<0.001 statistically significant (Student t test for age, Pearson's χ 2 for other variables). VICAN, VIe après le CANcer.

Funding This study was funded by The National Institute of Cancer (INCa), "Contrat de recherche et développement no 05-2011".

Author affiliations [START_REF] Kanavos | The rising burden of cancer in the developing world[END_REF] INSERM, UMR912 "Economics and Social Sciences Applied to Health & Analysis of Medical Information" (SESSTIM), Marseille, France [START_REF] Arnold | Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory[END_REF] Aix Marseille University, UMR_S912, IRD, Marseille, France 3 ORS PACA, Southeastern Health Regional Observatory, Marseille, France Collaborators Members of the VICAN Group: Thomas Aparicio, Emmanuel Babin, François Beck, Robert Benamouzig, M-KB, CB, Dominique Bessette, A-DB, Philippe-Jean Bousquet, Marie-Claude Cabanel-Gicquel, Marianick Cavallini-Lambert, Michèle Chantry, Claire Chauvet, SC, Véronique Danguy, Michel Dorval, Jean-Baptiste Herbet, Laetitia Huiart, Xavier Joutard, Anne-Gaëlle Le Corroller-Soriano, Julien Mancini, Mégane Meresse, Jean-François Morere, Herman Nabi, Alain Paraponaris, PP-W, Marie Preau, Christel Protiere, Frédérique Retornaze, DR, Benoit Riandey, Luis Sagaon-Teyssier, Aurélia Tison, VS, Archana Singh-Manoux, Catherine Thieblemont, Pierre Verger.

Contributors A-DB, M-KB, LST, DR, VS and PP-W contributed to the conception, design and management of the study. A-DB, CB, M-KB and PP-W contributed to the data collection. A-DB, M-KB, LST, SC, CB and PP-W contributed to the data analysis. A-DB, SC, LST, DR and PP-W contributed to the drafting of the manuscript. All authors critically revised successive drafts of the manuscript and approved the final version.

Competing interests None.

Ethics approval The study methodology was approved by three national ethics commissions: the CCTIRS (Comité Consultatif sur le Traitement de l'Information en Matière de Recherche dans le Domaine de la Santé, study registered under no 11-143), the ISP (Institute of Public Health, study registered under no C11-63) and the CNIL (French Commission on Individual Data Protection and Public Liberties, study registered under no 911290). Confidentiality is assured for all participants with regard to any personal responses and information provided, as all data collected are anonymised. Results of the study will be disseminated through national and international research conferences, and in articles published in international peer-reviewed journals.

Provenance and peer review Not commissioned; externally peer reviewed.

Data sharing statement The INCa will promote and organise open access to the dataset for all scientists interested in this survey before the end of 2014.


A Benchekri
email: aurelie.benchekri@univ-poitiers.fr

R Tisserand

C Bidet- Ildei

É Lemonnier

A Amestoy

L Fradet

Slow anticipatory postural adjustments during gait initiation in autistic children

Keywords: autism, gait initiation, anticipatory postural adjustment

Introduction

Autism Spectrum Disorders (ASD) are part of neurodevelopmental disorders characterized by persistent deficits in communication and social interactions, and restricted and repetitive behaviors, interests, or activities. Motor disorders are also part of the clinical phenotype of ASD [START_REF] Mosconi | Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder[END_REF]). Yet, because they remain poorly investigated and because the diagnosis still takes time to set up, it remains unknown whether the study of motor tasks may improve the process of identifying ASDs. By transitioning between posture and movement, gait initiation (GI) is a challenging motor task for balance control. The quality of posture-movement coordination during GI can be estimated by characterizing the anticipatory postural adjustments (APAs), a specific coordination that fulfills two complementary mechanical roles. First, they create a disequilibrium during the loading phase, through a backward and a lateral (towards the future swing foot) displacement of the Center of Pressure (CoP). This initial imbalance provokes a center of mass (COM) motion forward and towards the stance foot. Second, the COM motion is stabilized during the unloading phase, where the CoP moves towards the stance foot. Previous results of APAs performed by ASD children during GI reported a reduced mediolateral (ML) displacement of the CoP, suggesting a reduced ML stability [START_REF] Fournier | Decreased static and dynamic postural control in children with autism spectrum disorders[END_REF]. However, the authors did not distinguish the two APAs phases, thus leaving the mechanisms of reduced stability unclear. The objective of our study was to characterize APAs during GI in ASD and typically developing (TD) children by distinguishing the two phases.

Methods

Population

25 children diagnosed with ASD (10 girls, 8.7 ± 1.9 years old, 1.33 ± 0.16 m, 28.7 ± 12 kg) were recruited at the Limoges University Hospital and 31 agematched TD children (15 girls, 8.4 ± 1.4 years old, 1.34 ± 0.90 m, 29.8 ± 6 kg) were recruited in Poitiers.

Task and equipment

All children completed five GI trials. During each trial, children started from an upright standing posture, with each foot positioned on one force plate and their arms at their side. After at least 3s of quiet standing, children were verbally instructed to start walking at a comfortable speed to reach a ground mark about 3 metres away. Initial position of the feet was marked on the ground to ensure initial position repeatability. Ground Reaction Forces (GRF) were recorded using two adjacent force plates (Sensix® in Poitiers and Kistler® in Limoges) sampled at 1000 Hz. A Vicon 3D motion-capture system with 20 cameras sampled at 100 Hz recorded the trajectories of four reflective markers placed on foot anatomical landmarks (lateral and medial malleoli, second metatarsal head, and calcaneus).

Data analysis

The vertical component of the GRF (Fz) extracted from the force plate located underneath the stepping foot was used to identify three key instants (Fig. 1, left): APAs Onset (AO), as the first instant when Fz amplitude was larger than its mean + 3 SDs measured during the 3s of quiet standing; Foot-Off (FO), as the first instant when Fz was inferior to 2.5% of the child's weight; and Beginning of Unloading (BU), as the instant when Fz was maximal between AO and FO. These instants were then used to compute three durations: the total APAs (between AO and FO); the loading phase (between AO and BU); and the unloading phase (between BU and FO). Also, the trajectory of the CoP was extracted from the two force plates (Fig. 1, right). After filtering the CoP using a 2 nd order Butterworth filter with a 10 Hz cut-off frequency, its trajectory was characterized by its amplitude, in the AP and ML directions during the loading phase, and in the ML direction during the unloading phase. These amplitudes were normalized by the size of the base of support, estimated as the foot length and the feet width, measured from the feet markers, respectively in the AP and ML axes. AP and ML velocity peaks were also extracted during the loading and unloading phases, by taking the maximum of the time-derivative of the trajectory.

Statistics

Non-parametric Mann-Whitney tests were performed to compare the two groups for each dependent variable, with a threshold set at p < 0.05.

Table 1. Group effect on the different dependent variables. SD: standard deviation. M-W: Mann-Whitney test. AP: anteroposterior. ML: mediolateral.

Results and Discussion

ASD children displayed prolonged APAs during GI compared to TD children. This prolongation was principally consecutive to the lengthening of the unloading phase, during which the CoP also tended to move with reduced amplitude and velocity. Despite no duration difference between groups during the loading phase, the CoP of ASD children moved with reduced amplitude and velocity in the ML direction (Table 1). During the loading phase, laterally moving the CoP towards the future swing foot allows to drive the COM towards the future stance foot, increasing the mediolateral stability conditions at foot-off. With reduced amplitude and velocity during the loading phase, the mechanical consequences of APAs produced by ASD children should drive the COM with reduced velocity towards their stance foot. Consecutively, ASD children may need to wait longer during the unloading phase for the vertical projection of their COM to come close enough to the stance foot to be able to lift the swing foot. This may explain why, in line with previous research, ASD children displayed a prolonged unloading phase with reduced CoP movement compared to TD children [START_REF] Fournier | Decreased static and dynamic postural control in children with autism spectrum disorders[END_REF]). Together, our results suggest that the main difference between ASD and TD children resides in the ML direction for balance control of GI. These results seem to corroborate previous observations reporting differences between ASD and TD children in the ML axis during maintenance of an upright standing posture [START_REF] Lim | Standing Postural Control in Individuals with Autism Spectrum Disorder: Systematic Review and Meta-analysis[END_REF]). In the control of upright standing postures, it is assumed that hip muscles are mostly responsible for CoP lateral displacements. Therefore, ASD children may have difficulties with hip muscle force production and/or hip muscles coordination control [START_REF] Lim | Standing Postural Control in Individuals with Autism Spectrum Disorder: Systematic Review and Meta-analysis[END_REF]. Difficulties in coordination control may also come from immature body representations consecutive to altered sensorimotor integration during motor tasks [START_REF] Assaiante | Construction des représentations de l'action chez l'enfant : quelles atteintes dans l'autisme ?[END_REF]. Among the neural structures involved in motor control, one of the best candidates for ineffective balance control if altered is the cerebellum because it is at the crossroads of ascending and descending sensorimotor functions [START_REF] Mosconi | Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder[END_REF].

Conclusions

In summary, we showed that ASD children have slow APAs during GI. This slowness suggests ASD children would end GI with reduced dynamic stability in the mediolateral direction. These balance deficits may be explained by alterations in hip muscles and/or sensorimotor control going through the cerebellum. GI seems to be a relevant paradigm to identify motor alterations in ASD children, yet more research is necessary to disentangle the origins of these impairments.

APAs

Mean

Figure 1 .

 1 Figure 1. Temporal evolution of the stepping foot GRF during GI with the three key events AO, BU, and FO (left) and top view of the CoP trajectory during GI (right).

Acknowledgements

This work was supported by the Region Nouvelle-Aquitaine.