Medical Outcomes Trust March 1997 BULLETIN

Glaxo Wellcome is likely to be the most notable user of the Asthma Quality of Life Questionnaire (AQLQ) not only because of the company’s 7,000-8,000 administrations of the questionnaire in approximately 22 studies over the past several years, but due to the recent achievement of making an asthma-specific quality of life claim for which the FDA agreed that there was sufficient data based on quality of life research to support the claim. In an interview with Fred Cox, PhD, Associate Director, Pharmacoeconomic Research-Medical Affairs of Glaxo Wellcome, the Bulletin learned about the history behind this most significant event.Three years ago, a series of studies were designed and conducted by Glaxo Wellcome to answer the following question: is salmeterol xinafoate (Severent®) actually improving the quality of life of patients with asthma? This drug had demonstrated good efficacy and safety, but its humanistic impact was not clearly understood.

Dr. Cox indicated that "although other quality of life measures had been used by Glaxo Wellcome in asthma studies, as compared to the AQLQ, most were found to be less sensitive to change or less able to differentiate between treatment groups." The AQLQ was ultimately chosen by Glaxo Wellcome for several reasons; all of which were principally driven by the desire to appropriately assess this area with scientific vigor and to eventually make promotional claims based on the results of their studies. Realizing that the FDA would require a questionnaire with strong evidence of validity and reliability, a significant history of use, and the ability to detect meaningful changes in a patient’s quality of life. Dr. Cox and his colleagues reviewed several measures in the planning phases of the studies.

In this review, the AQLQ appeared to meet the requirements of psychometric strength and use history, and included values for assessing relevant change with a three-tier benchmarking scale for small, moderate and large changes. The AQLQ has been validated across a wide variety of asthma patient populations with varying severity levels, and it allows the patient the ability to individualize the activities that are impacted by asthma. The patient may select, at baseline, five activities that: are impacted by their asthma, are important to them, and are expected to remain important to them during a specified period of time. Other questionnaires preselect these activities, and Dr. Cox believes that in large studies in countries like the U.S. with many ethnic, and socioeconomic groups this feature of the questionnaire is an important strength. In addition, the decision to use the AQLQ was influenced by the fact that the scale is multidimensional, andincludes domains that are relevant to asthma (activity limitation, asthma symptoms, emotional function and enviornmental stimuli), and a global score can be calculated.

A series of eight studies (four paired studies in a 12-week double blind randomized placebo controlled design) were conducted with the primary objective of assessing the impact of salmeterol xinafoate (Severent®) on asthma-specific quality of life. Each pair of studies addressed a different asthma population, and just over 2,000 patients were enrolled. No other quality of life questionnaire was used in the study.

In over 200 U.S. study sites, the AQLQ was self-administered to enrollees at baseline prior to treatment, and again at Week four, Week eight and Week twelve. Results were examined looking at improvement from baseline. Mean score changes were compared from baseline between treatment groups. Individual domain scores were evaluated as well as global scores. Results of the studies have been presented at several national and international scientific conferences during the past year.

For one pair of these studies, the FDA agreed that GlaxoWellcome had sufficient data to support an asthma-related quality of life claim stating that salmeterol xinafoate provides significantly greater improvement in asthma-specific quality of life as compared to PRN albuterol. This agreement with the FDA has allowed GlaxoWellcome to provide not only patient outcome information regarding asthma management with salmeterol but also educate the health care community about disease-specific quality of life.

Dr. Cox is confident that Glaxo Wellcome has developed a model that works. He highlights the success of this initiative by identifying three key principles that were integral in the design and completion of these studies. First, select a competent ( i.e., valid, reliable and responsive) instrument. The FDA wants good science and good results. During their interactions with the FDA, Glaxo Wellcome invited Elizabeth F. Juniper, MCSP, MSc (the developer of the questionnaire) to present about its development, its purpose and how it is interpreted. The second principle is to make health related quality of life a primary objective of the study and to pay a great deal of attention to the actual conduction of the study. Monitor for issues such as appropriate questionnaire completion, adequate staff training, data integrity, and overall quality control. Finally, understand your results. Make them meaningful to the health care community with the ultimate aim of impacting how patients are managed.

Dr. Cox also remarked on the tremendous positive response to quality of life assessment received from the clinicians who served as principal investigators of the studies, and the patients enrolled in the studies. He believes that both parties recognized the importance of these types of questionnaires, and it has been noted that "the AQLQ is a standardized way of asking questions of patients with asthma what a good clinician should ask them."

The Medical Outcomes TRUST is pleased to announce the recent approval and current availability of three Asthma Quality of Life Questionnaires: the Adult Asthma Quality of Life Questionnaire, the Pediatric Asthma Quality of Life Questionnaire, and the Pediatric Asthma Caregiver’s Quality of Life Questionnaire for parents or primary caregivers. The principal developer of the Asthma Quality of Life Questionnaires is Elizabeth F. Juniper, MCSP, MSc of McMaster University Medical Centre in Ontario.

The Asthma Quality of Life Questionnaires are designed to identify items of quality of life impairment that are of potential concern for adults, and children with asthma and their care givers. Development of the original Asthma Quality of Life Questionnaire intended for adults with asthma grew out of the recognition that asthmatic patients are bothered daily by various problems other than diagnosable symptoms like shortness of breath. The adult questionnaire measures the effect of symptoms and other aspects of illness on patients’ lives on a day-to-day basis. Concepts represented in the instruments are symptoms, emotional function, exposure to environmental stimuli, and activity limitations. The inclusion of an assessment of emotions associated with having the illness such as fear of not having medication when needed is particularly relevant for the care of asthmatic patients. A brief description of each of the three questionnaires including their intended application and scope follows.

The Adult Asthma Quality of Life Questionnaire (AQLQ) is a disease-specific quality of life questionnaire primarily designed to evaluate change in patients’ quality of life over some period of time. For example, one may wish to measure the extent to which a new asthma drug affects the quality of life of a patient over a two month period. The AQLQ would be administered at the beginning of the drug regimen and again at the end of the two month period.

The AQLQ contains 32 items that measure four dimensions of health: 12 items assess symptoms, five items measure emotional function, four items assess exposure to environmental stimuli, and eleven items focus on activity limitations. The instrument can be self-administered or given as an interview. In either form, typically the questionnaire takes five to ten minutes to complete. Individual items within the AQLQ are equally weighed. The questionnaire is analyzed directly from the scores recorded and the results are expressed as the mean score per item for each of the domains as well as for overall quality of life (i.e. both the domain and overall scores range from one to seven). So, for instance, the results from a domain with four items and a domain with eleven items will both be expressed as a score from one to seven. This facilitates the interpretation of results. Overall quality of life score is estimated from the mean score of all items.

Development of the Asthma Quality of Life Questionnaire was the result of a study that evaluated the impairment of health related quality of life in asthma. The 150 adults enrolled in the study participated in a structured interview during which they identified parts of their daily lives affected by asthma. Areas of quality of life impairment reported included symptoms traditionally associated with asthma as well as responses to environmental stimuli, the need to avoid these stimuli, activity limitations, and emotional dysfunction.

The Pediatric Asthma Quality of Life Questionnaire (PAQLQ) was constructed from data collected from a study of children with asthma. Subjects, ages 7-17 years and representing a range of asthma severity were presented with 77 items that included all potential functional impairments. Items which were scored the highest and were identified most frequently by patients were chosen for the PAQLQ.

The PAQLQ is appropriate for asthmatic patients between the ages of 7 and 17 years. The PAQLQ includes 23-items in three domains. Ten items assess symptoms, eight items concerning emotional function, and five items regarding activity limitations. The three items of the activity domain are personalized by the patients’ indication of three activities that are important and are done frequently but are impaired by the asthma. The PAQLQ is designed for administration in the absence of parents. Like the AQLQ, the PAQLQ can be either self-administered or given as an interview.

The Paediatric Caregiver’s Asthma Quality of Life Questionnaire (PCAQLQ) is a 13-item questionnaire. This questionnaire contains nine items regarding emotional function and four items concerning activity limitations. It is a self-administered questionnaire and takes five to ten minutes to complete.

Development of this instrument was prompted by the observation of the impact of the illness on the quality of life of people connected to the patient. The PCAQLQ was designed to measure the effect on parents whose lives typically are considerably changed on account of their child’s illness. The instrument is able to detect quality of life changes. It is also able to distinguish between those whose quality of life has changed and those whose has remained the same. The PCAQLQ is valid both as an evaluative instrument and a discriminative instrument.

The availability of the Asthma Quality of Life Questionnaires clearly addresses the need for an instrument to measure health-related quality of life in patients with asthma. They encourage an approach to care which asks those effected about the impact of asthma on their lives. This approach includes consideration of the perspectives of the patient, adult or child and the caregiver. These instruments are valuable in that they are offer insight into the impact of asthma by assessing the extent of improvement and deterioration in quality of life over time and distinguish between respondents with minor and more serious impairment of quality of life.

References
Juniper, E.F. et al. Evaluation of Impairment of Health Related Quality of Life in Asthma: Development of a Questionnaire for use in Clinical Trials. Thorax. 1992;42: 76-83
Juniper, E.F. Juniper, E.F. et al. Measuring Quality of Life in Children with Asthma. Quality of Life Research. 1996.5: 35-46
Juniper, E.F. et al. Measuring Quality of Life in Parents of Children with Asthma. Quality of Life Research. 1996.5: 27-34

A recent study conducted by Barbara Berkman, DSW of both the Columbia University School of Social Work and the Department of Social Services at the Massachusetts General Hospital, and her colleagues examined the use of patients’ perspective in assessing the need for social work intervention. Results indicate that standardized

measures of health status, such as the SF-36 Health Survey, when supplemented with specific social work assessment items, are valuable in identifying the psychosocial needs of the elderly and may provide an accurate indication of need for social work care.

Sighting the numerous and confounding problems that the elderly potentially encounter—from physical illness to social isolation—Dr. Berkman, conducted a study investigating this experience from the patient’s perspective. Given the range of needs of the elderly patient, medical care of the elderly demands a comprehensive approach that includes assessment of complex medical problems, functional capabilities, social-environment supports and emotional well-being.

Berkman found that the use of standardized health status assessment among the elderly could be beneficial to the patients and their medical providers by quickly and accurately providing an assessment of factors such as physical functioning and mental health. Such an assessment would help prevent complications with illness due to delayed diagnosis thereby maintaining health and enhancing quality of life. She argues that standardized health assessment would support the work of the primary care physicians by relieving them of the burden of acting as case managers in the coordination of non-medical care. Use of a standardized health assessment would also help primary care physicians respond to the overall health concerns of patients. As a screening for need for social work intervention, a standardized health assessment would facilitate prevention and eventually may prove to reduce costs. For example, elderly patients who may over utilize their primary care physician’s office, using their physician as a psychosocial support could

be better served by early identification of their needs which can be provided by a standardized health assessment and early intervention by the social worker. This may save the doctor and patient time and money, and lower the patient’s health care claim costs. For hospitals, the benefits may be as small as having as social worker refer a primary care patient to a hospital-related service, or as large as avoiding the expensive hospitalization of an elderly patient.

Berkman used the SF-36 Health Survey to assess the needs of elderly primary care patients at Massachusetts General Hospital (MGH) in order to determine the feasibility of using the instrument for screening psychosocial needs and subsequently the need for social work intervention. For the purposes of the study, additional questions specifically aimed at assessing the types of problems dealt with by social workers were incorporated to create the SF-36 plus Social Work questionnaire. These additional questions measured physical, social, and mental health in addition to socioeconomic and environmental factors. Questions were included about health, such as daily medications and recent hospitalizations as well as questions regarding marital status, living situation or care giving arrangements to measure socio-environmental factors in a person’s social support network and/or community resources. Other questions such as, "Do you have difficulty managing money, paying bills, or paying for medications?" addressed concerns related to socioeconomic factors. These additional questions were believed to enhance the scope of the SF-36, particularly the ability of the instrument to assess psychosocial needs of the elderly and emphasize specific factors that would indicate the need for social work assessment.

This supplement also created a comparison between responses to social work-specific questions and scores on SF- 36 scales which allowed Berkman to see which psychosocial needs were already addressed by the SF-36.

The SF-36 plus Social Work was self-administered by 313 patients, 65 years and older who were scheduled for visits at the primary care practices of MGH. A social work care coordinator reviewed the responses to both the SF-36 and the additional questions. While all patients’ responses were rated based on whether they would benefit from social work services, only those patients in the experimental group for whom intervention was determined necessary received services. Patients in the control group neither were contacted about their possible need for intervention nor were given services.

Berkman’s work emphasizes aspects of the SF-36 which should be considered when focusing on the elderly population. Factors such as whether or not a patient is able to complete the questionnaire independently should be considered when choosing an administrative format. Other factors such as poor eye sight, education level, cultural bias and sensitivity to topics like sex and drug abuse should also be considered in surveying the elderly. In this study, a mailed questionnaire proved to be more successful than distribution to patients waiting for appointments in their doctors’ offices because secretaries asked to distribute the questionnaires to patients were inconsistent, giving questionnaires to those whom they thought needed services instead of providing all patients 65 years and older with questionnaires.

Findings suggest that the SF-36 captures some important psychosocial risk factors in the elderly, such as problems with IADL’s. However, the SF-36 alone does not seem to touch upon other specific difficulties which are necessary in predicting need for social work intervention. Berkman recommends revision of the SF-36 for future studies of the elderly since results show that the SF-36 plus Social Work is useful, despite repetitive questions, in assessing the psychosocial needs of the elderly.