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- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease known for the diversity of its clinical manifestations. The disease prevalence is approximately 42 of every 100,000 adults. SLE tends to occur in young women of reproductive age (1, 2). Lupus nephritis is the renal manifestation of lupus, which affects 40% of SLE patients at some stage of the disease (3, 4). Lupus nephritis leads to progressive loss of renal function and may eventually require dialysis or transplantation, or result in death (5, 6). The current 5-year survival rate is 82% and is increasing (7). The current treatment for lupus nephritis calls for aggressive immunosuppressive therapy, starting with an induction phase and followed by a maintenance phase (8, 9). Rheumatologists consider combined cyclophosphamide (CYC) and steroid pulse therapy to be the gold standard for the first phase, due to its ability to keep the disease from progressing to end-stage renal disease. Other drugs are available, such as mycophenolate mofetil (MMF), an immune suppressant originally approved for renal transplantation (10). CYC must be administered in a day hospital setting once a month for at least 6 months. Nausea and vomiting may occur during infusion. Therapy with CYC provides an 85% chance of controlling disease activity for 5 years (11). It can potentially lead to the development of myelosuppression, hemorrhagic cystitis, opportunistic infections of different severities, malignancies, and premature gonadal failure. Daily doses of oral MMF have been suggested in situations of therapeutic failure or intolerance to CYC. Literature references suggest that MMF has a similar potential to reduce lupus nephritis complications, as does CYC, but with less risk of adverse events (12). Lupus nephritis treatment options differ in method of administration, the potential for positive and negative outcomes, and the likelihood of sustained remittance of active disease (13, 14). By understanding these differences, patients can assess their preferences and participate in treatment decisions in an enlightened and rational manner (15, 16). Decision support tools (17, 18) may be used to ensure that the physician uses standard language that is as free as possible of any bias when describing treatment options. A decision board (DB) is an inexpensive and user-friendly tool that can be used in a clinical setting (19). The literature does not describe any DB for lupus nephritis. In addition, the authors were unable to find any decision-making support tool tested in patients with few years of schooling. The objective of this study was 1) to describe the steps in developing a DB tool to support the decision-making process and 2) to assess the reliability and face, content, and construct validity of the DB.
PATIENTS AND METHODS
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
The study involved patients with SLE treated at the Federal University of Sao Paulo. Sample recruiting was random and based on convenience. Patients were selected on the day of their medical consultation. The criteria for eligibility were as follows: women ages 18–50 years with a 6-month or longer diagnosis of SLE according to the modified classification criteria published by the American College of Rheumatology (20, 21) and any clinical manifestation of the disease. This study did not include men given the low incidence of SLE in this sex. In addition, patients had to be able to read and write. Patients presenting active psychosis or any form of cognitive disability were excluded, as were patients whose records were unavailable at the time of patient assessment and selection. All participants signed a Statement of Free and Informed Consent. The institution's committee for ethics and research formally reviewed and approved the project. This was a cross-sectional study.
The literature has not yet described a gold standard that physicians can use to enable patients to list their treatment preferences and thus participate in the decision. Therefore, the most appropriate method to test the validity of a tool is construct validity (22–24). Following the recommendations of the International Patient Decision Aid Standards (25), a 4-step approach was used to develop and test the DB. These steps were selected according to similar studies that assessed the DB in the context of oncology pathologies such as breast and ovarian cancer (26–30). The reproducibility and validity of these tools were tested, and their effectiveness has been proven by other studies, including 1 clinical trial (31). Thus, the process included the following steps: 1) developing the instrument: content design and assessment; 2) calibration: pilot study; 3) deployment; and 4) assessment of the measurement properties (reliability, face validity, content validity, and construct validity) (26–30).
Step 1: designing the instrument: formatting the content
The purpose of this phase was to develop the DB, guided by 3 basic issues: Does the content reflect the best/latest evidence available in the literature? What is truly relevant to the patient, in the sense that it can be assessed by the patient and used as input in a process of informed decision making? How should the content be presented?
The first issue was addressed with a thorough literature search for studies discussing the decision-making process, patient preference, SLE, and lupus nephritis. Of the 22 publications that attempted to assess preferences in patients with SLE, only 3 included lupus nephritis. None of these studies used any type of decision support tool for this purpose. Sixty-nine studies were found mentioning “decision aids” and “systemic lupus erythematosus.” Unfortunately, we excluded these because they dealt with laboratory methods, which are outside the scope of this study. “Shared decision making” and “systemic lupus erythematosus” yielded 2 reviews on the psychosocial and economic aspects of the disease (32, 33). “Treatment” yielded 2 relevant studies that compared MMF and CYC (12, 34). Additional treatment data were extracted from Cochrane's review on all of the available treatments for lupus nephritis (35).
A preliminary version of the content was developed and submitted to the panel of experts made up of rheumatologists, an educator specializing in medical education, and an epidemiologist (26–30). The first group of specialists (rheumatologists) provided input on the clinical relevance of the content, and made whatever adjustments were necessary to reflect the reality of the clinic in which the study was developed. The other experts assessed the didactics and the verbal and written language used to present the DB, with particular care taken with how the numbers describing the probabilities of the different outcomes were presented.
Step 2: study development and calibration: pilot study
A pilot was used to improve the clarity of data and the presentation of the numerical data (27, 31). This step produced changes that primarily had to do with the format used to present probabilities or likelihoods to the patients.
Step 3: using the tools: final structure and strategy for using the tools
The final DB structure consisted of 5 parts, each presented separately during the patient interview. At this point we had 1) a concise text containing general information on SLE and lupus nephritis, including general data on prevalence and possible negative outcomes for patients who declined treatment; 2) therapeutic information: 2 treatment options were presented, including the method of administration, posology, and the real chances of remission associated with each; 3) a list of the 8 most probable side effects, according to the literature; 4) patient selection of the 3 worst side effects from this list; and 5) patients who were were informed of the probability that each of the 3 worst side effects chosen would occur in each of the treatment options presented. Option 1 referred to therapy with MMF and option 2 to therapy with CYC. The outline of the DB that was submitted to each interviewee is shown in Figure 1.
Figure 1. Schematic representation of the decision board. At first, patients are shown only chart A, followed by charts B and C with only the subtitles visible. The content is filled out during the course of the interview. A, Summary presentation of disease information, with an emphasis on lupus nephritis. B, A description of the treatment options: method of administration, likelihood of remission, and a list of the 8 potential side effects that the literature reports as having the highest prevalence. C, Data on the probability of experiencing each of the 3 side effects selected by the individual interviewee as the most undesirable.
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The Brazilian Public Healthcare System only offers CYC to lupus nephritis patients. The average monthly cost of MMF therapy is approximately 10 times the cost of CYC. Although the literature suggests that cost has an impact on patient health care decisions, we excluded costs from the scenarios to eliminate any possible bias based on elements outside the focus of this study (i.e., the preference for a treatment regardless of its financial consequences). All of the options were presented as cost-free to the patients.
The final format was a 60 × 80–cm chart. Except for the title, subtitle, and introductory text describing the disease in general terms, the DB started out blank. Information about treatment options and details of the side effects that patients considered to be one of the 3 least desirable were attached to the chart with Velcro as the interview progressed (Figure 1).
First, we described the objective of the study, followed by a clinical evaluation that included the patient's history, a standard clinical questionnaire used to assess disease activity (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]), and chronicity (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]) in SLE (36, 37).
Second, the DB was introduced individually during the course of the interview.
Third, understanding was assessed. Once patients were familiar with the chart and had reviewed the content, they used the following scale to assign a score to their understanding of the material: 0–2 = no understanding at all, 3–4 = some understanding, 5–6 = moderate understanding, 7–8 = significant understanding of the content, and 9–10 = full understanding (38, 39).
Fourth, a therapeutic option was selected.
Fifth, treatment options were justified and the justification was classified into 4 groups: risk, effectiveness, risk-benefit tradeoff, and practicality. The risk group included patients who considered what they felt to be the worst side effects as essential to their treatment decision. The effectiveness group included patients who based their decision on the probability that the treatment option would control disease activity. The tradeoff between risk and benefit group included patients who tried to take into account all of the issues involved in both treatment options, including the probability of controlling the disease and the likelihood of the most undesirable side effects. The practicality group included those patients whose main decision-making criteria were method of administration and to what extent administration would hinder day-to-day activities.
Finally, following the clinical evaluation, interviewees were asked to complete the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to assess quality of life. Previous studies have already translated and tested the validity of the Portuguese version of the questionnaire (40, 41). Additional clinical data were obtained from a review of patient records.
Step 4: assessment of the properties of the psychometric measures: reliability and face, content, and construct validity.
The reliability test was conducted by the same observer (test and retest). Patients were asked to return to the hospital and retake the test 15–30 days after the first interview. The criterion used to select patients for this phase was no need to change the therapeutic conduct before the date of the second interview. Of all the patients, 30% were interviewed a second time.
Face and content validities
Face validity is a subjective concept that refers to the appearance of the tool. To examine this property, we compared the characteristics of the tool based on its similarities with other types of decisions, particularly with other DBs (23, 24).
Content validity refers to the ability of the items in a measuring instrument or test to adequately represent the content that the investigator wishes to measure. It has to do with the potential for execution, clarity of content, simplicity of exposure, likelihood of bias, and presence or absence of redundant items (23, 24, 31).
Conceptually, the construct validity of an instrument measures what is being inferred and if the inferences are accurate. This involves comparing measurements and examines the logical relationships between measurements and the characteristics of a patient or group of patients (23, 24, 28, 31, 42, 43).
DB is a tool to help assess patient preference using the following parameters: 1) selection of the 3 worst side effects, 2) patient understanding of the content described in the tool, and 3) the option for treatment. To measure preference consistency, we tried to measure the impact of clinical, social, educational, and quality of life parameters on the decision-making process in light of the described scenario (42). The constructs tested were based on the following hypotheses.
The first hypothesis was that the selection of the 3 least desirable side effects reflects patient preference, and will influence the treatment decision. DBs were customized based on the 3 most bothersome side effects selected by each interviewee. The expectation was that the life-threatening side effects associated with the options would lead participants to select option 1, given that this option provided the smallest likelihood that such side effects would actually occur. To test this hypothesis, the 8 side effects were grouped according to 2 variables, life threatening and non–life threatening, and then correlated with the final treatment option (option 1 or option 2). This construct measures the impact of the content included in the DB on stated patient preferences (17, 18, 44).
The second hypothesis was that the content presented in the DB designed for this study is clear and easy for all patients to understand. Patient understanding of the DB content was self-assessed. To check the hypothesis of this construct, self-assessment scores were correlated to years of schooling. The authors expected that patients would have high self-assessment scores, regardless of the years of schooling. This would support the hypothesis that the DB is a potentially feasible tool for clinical practice, as this construct measures content clarity and ease of understanding for patients (17, 18, 45, 46).
The third hypothesis was that personal clinical history influences patient decisions. Patients with a degree of severity tend to rate side effects based on the extent to which they are life threatening. They also tend to opt for the most effective treatment and would therefore turn down option 1. In this study, severity required fulfilling at least 1 of the following criteria: 1) prior or current CYC use; 2) prior and/or current use of immunosuppressive drugs; 3) enhanced disease activity, defined by a SLEDAI score of 8 or more; and 4) enhanced chronicity, defined as an SDI score of 5 or more. Severity was adopted as a dichotomous variable. The hypothesis for this construct was that patients presenting at least 1 of the parameters that define disease severity would tend to turn down option 1, given that it offers less of a chance for controlling the disease. This construct measures the impact of personal clinical history on patient decisions (17–19, 47, 48).
Descriptive analysis measured the distribution of the demographic and socioeconomic variables (49). The following variables were grouped together to improve the quality of the statistical analysis: 1) selected side effects (life threatening and non–life threatening), 2) self-assessment scores (high levels of understanding [a score of 7 or higher] and moderate understanding [a score below 7]), and 3) years of schooling (significant schooling [9 or more years] and little schooling [fewer than 9 years]).
Reliability (test and retest) was checked using kappa test. Pearson's chi-square test (categorical variables) and Fisher's exact test (categorical variables for subgroups of samples <50) were used to verify the hypotheses used to build the validation process. These tests look for discrepancies between observed and expected frequencies. The nonparametric tests used were the Wilcoxon's test for ordinal paired variables and the Mann-Whitney test for ordinal nonpaired variables. Spearman's correlation coefficient was used to assess the correlation between nonparametric variables (49, 50). For all statistical tests, the level of significance used was 5% or less. Statistical analyses were conducted using SPSS software, version 13.0 (SPSS, Chicago, IL).
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- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
Between April 2005 and March 2006, 172 patients were interviewed. The refusal rate was 4%. The demographic and socioeconomic profile of the patients is shown in Table 1. The mean ± SD age was 34.3 ± 8.34 years. Racial distribution was 45.3% Mestizo, 39.5% white, 13.9% African Brazilian, and 1.3% Brazilian of Asian descent (51). Average household income was the real equivalent to 500.00 (US dollars) per month. Disease profile distribution was heterogeneous (Table 2). Of all patients, 38.9% had been diagnosed between 1 and 6 years previously; 75% had had renal involvement, and 55% had received pulsed therapy with CYC for a specific clinical reason. Seventy-five percent of all patients had taken or were taking some sort of immunosuppressive drug. In terms of quality of life, the average scores for the Brazilian version of SF-36 were low, especially in the categories of pain, overall health, and vitality. It took a mean ± SD of 20 ± 11 minutes to apply the DB. Iatrogenic cancer was the most frequent side effect selected (44.2%), followed by hair loss (21.6%) and infection (19.1%). Of the 8 side effects, we found that those that pose a threat to life were most often mentioned by patients as one of their 3 worst side effects. Option 1 (oral medication) was selected by the overwhelming majority of patients (68%). The decision justifications were risk (47.7%), effectiveness (12.2%), risk-benefit tradeoff (2.3%), and treatment practicality (37.8%). Reliability was assessed in 52 patients (30%). The selection of side effects was reproducible. For the first side effect, we found a kappa of 0.334 (P < 0.001); for the second side effect, kappa was 0.202 (P < 0.001); and for the third side effect, kappa was 0.220 (P < 0.001). The final option was also reproducible (κ = 0.757, P < 0.001), as were the self-assessment scores (κ < 0.354, P < 0.001). The treatment option was similar to that found in the test phase (κ = 0.689, P < 0.001).
Table 1. Demographic and socioeconomic characteristics of the evaluated population (n = 172)*
|Age, mean ± SD years||34.3 ± 8.34|
| White||68 (39.5)|
| African Brazilian||24 (13.9)|
| Mestizo||78 (45.3)|
| Ethnic Asian||2 (1.16)|
|Marital status|| |
| Single||58 (33.75)|
| Married||95 (55.2)|
| Divorced/separated||16 (9.3)|
| Widowed||2 (1.16)|
| Other||1 (0.59)|
|No. of children|| |
| 0||58 (33.72)|
| 1–3||107 (62.21)|
| ≥4||7 (4.07)|
|Housing status|| |
| Rented premises||51 (29.6)|
| Own premises||88 (51.2)|
| Other†||33 (19.1)|
|Level of education|| |
| Primary/middle school||77 (44.6)|
| High school graduate||80 (46.5)|
| College graduate||12 (7)|
| Graduate school||3 (1.9)|
|Employment status|| |
| Employed||49 (28.50)|
| Unemployed||123 (71.50)|
|BECC (income, in US$ equivalents)|| |
| A1 (3,000.00)||0 (0.0)|
| A2 (2,100.00)||2 (1.2)|
| B1 (980.00)||7 (4.1)|
| B2 (550.00)||31 (18.0)|
| C (327.00)||87 (50.5)|
| D (212.00)||44 (25.5)|
| E (103.5)||1 (0.6)|
Table 2. Clinical characteristics of systemic lupus erythematosus patients included in the study (n = 172)*
|Disease duration, years|| |
| <1||9 (5.2)|
| 1–6||67 (38.9)|
| 7–13||52 (30.2)|
| ≥14||37 (21.5)|
|Lupus nephritis|| |
| Yes||129 (75)|
| No||43 (25)|
|Cyclophosphamide use prior to or during the study|| |
| Yes||94 (55)|
| No||78 (45)|
|Immunosuppressant drug use prior to or during the study|| |
| Yes||129 (75)|
| No||43 (25)|
|ACR classification criteria|| |
| Malar rash||21 (12.2)|
| Discoid rash||11 (6.4)|
| Photosensitivity||27 (15.6)|
| Oral ulcer||6 (3.5)|
| Arthritis||144 (83.7)|
| Serositis||45 (26)|
| Renal disorder||77 (44.8)|
| Neurologic disorder||16 (9.3)|
| Hematologic disorder||36 (21)|
| Immunologic disorder||105 (61)|
| Antinuclear antibody†||165 (96)|
Construct 1 (Table 3) assessed the impact of the content described in the DB preference, and confirmed our expectations that the variable “life threatening” would steer decisions in favor of option 1 (χ2 = 0.047, P < 0.001). Construct 2 (Table 4) demonstrated the relationship between self-assessment scores and years of schooling, and clearly showed that 60% of patients with more than a high school education and 40% of patients with a high school diploma or less assigned themselves high scores (>7), suggesting that the DB content was easily understood. Regardless of years of schooling, all patients showed good levels of content understanding, although high scores were found more often in patients with a higher level of schooling.
Table 3. Assessing the impact of the side effects selected in the lupus nephritis decision scenarios according to the scenarios described in the decision board
|Dependent variable||Independent variable||Reason||Expected direction of association||χ2||Observed direction of association|
|Option 1||Side effects ranked based on how life-threatening they are.||A tendency to select option 1 as it offers a lower probability that these will actually happen.||Convergent||0.047||Convergent|
Table 4. Correlation between self-assessment scores given for understanding the content of the decision board and years of participating patient schooling*
|Self-evaluation score||Above average years of schooling (%)||Below average years of schooling (%)||Total|
Construct 3 (Table 5) tested the impact of the severity of disease on the treatment decision. We found that “prior use of immunosuppressive drugs” was significant (P = 0.055) for the final treatment option (P = 0.055). None of the other clinical variables had statistically significant correlations.
Table 5. Correlation between personal clinical history and decisions made in light of the scenarios described in the decision board (DB)*
|Dependent variable||Independent variable||Reason||Expected direction of association||P||Observed direction of association|
|Least desirable side effects selected||Lupus nephritis||A personal clinical history similar to the DB scenario may influence the side effects appointed as least desirable||Convergent|| ||Divergent|
| ||SLEDAI >8|| || ||0.861|| |
| ||SDI >5|| || ||0.179|| |
| ||Cyclophosphamide|| || ||0.072|| |
| ||Immunosuppressive drugs|| || ||0.065†|| |
|Option 1||Lupus nephritis||Patients with more severe disease tend to turn down option 1 as it is the option that provides the highest probability of being able to control the disease‡||Convergent||0.446||Divergent|
| ||SLEDAI >8|| || ||0.216|| |
| ||SDI >5|| || ||0.308|| |
| ||Cyclophosphamide|| || ||0.065|| |
| ||Immunosuppressive drugs|| || ||0.065†|| |
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
SLE patients are often faced with critical decisions (12, 52). These decisions involve personal values that may be found or explored with tools such as a DB (15, 16). This study made systematic use of standard information to develop a lupus nephritis DB that can be used as a tool for a more patient-involved decision-making process. Originally, the tool was structured to focus on the practical clinical reality of the institution where it was developed. There are several types of aids to support treatment decisions (25, 31, 43, 53, 54). The frameworks used and the major issues of concern to researchers in this area vary (43, 54). Decision trees and Markov models are other possibilities to offer information about the available treatment or to help patients make informed treatment decisions (55, 56). The Comprehensive Health Enhancement Support System (CHESS) is another option (57). CHESS is a computer-based system of integrated services designed to help individuals cope with a health crisis or medical concern. It was developed by an interprofessional team of decision-making, information, education, and communication scientists (57). The purpose is to improve informed decision making (57).
We chose to use a DB because our goal was to develop a decision aid that will help clinicians communicate treatment options to their patients (54). In addition, we chose the DB because one of the researchers is familiar with its use in a different clinical setting (i.e., cancer) (28, 29, 53, 58–60). The DB was tested extensively (including in a randomized trial) (29) and found to be effective in conveying to patients the potential benefits and side effects of different treatment options, which was the goal of our study. We hoped that better informed patients could be more involved in the deliberation about the choice of treatment.
The study was carried out in Sao Paulo. Census data for the Sao Paulo region show that the distribution of demographic characteristics of Sao Paulo compared with other major metropolitan areas in Brazil is similar in terms of years of schooling and occupation (61). This information, together with the historic and geographic elements of demographic distribution in Brazil, corroborates the statement that Sao Paulo summarizes this country's cultural diversity (61–64). A significant body of evidence supports our statement that Sao Paulo reflects the cultural, educational, and employment situation of the rest of the country, which adds to the study relevance, given that the population is believed to culturally reflect the rest of the country (61–64).
The side effects listed most often were drug-induced cancer, serious infection, and hair loss. An assessment of the psychometric properties of the tool shows that the DB is reproducible and valid. The self-assessment scores were also reproducible, although slightly higher on retest, suggesting that the DB contributes to the patient's overall understanding of the pathology. The treatment decision favored by participants was option 1. Practicality was the characteristic most often mentioned by participants who selected option 2 to treat their lupus nephritis. An interesting result was that current or prior use of immunosuppressive drugs was the only significant variable. The impact of a patient's clinical history on how decisions are made and the degree of treatment compliance are also not clear, whether in hypothetical situations or in actual life. Other studies that assess patient preferences suggest similar results, although none made use of a support tool (47, 52, 65, 66). We still do not understand the factors that could influence these decisions. There is a need for studies to explore this area (47, 52, 65, 66).
This study has some limitations. First, one of the important characteristics of any decision tool is that there should be a version that patients can take home (24, 25, 31), enabling them to reflect on the content and get input from people who are important to them. In this study, patients were asked to make their decisions during the course of the interview. Another limitation is that, although all study patients had SLE, not all had the clinical manifestations of lupus nephritis. For the purposes of developing this instrument, we asked patients to assume the hypothesis that they indeed had lupus nephritis. The authors recognize that decisions made based on a hypothetical scenario may not necessarily reflect the decisions made when faced with a real scenario. Nevertheless, this recourse does not significantly differ from those used in other publications discussing this same theme.
Another limitation is how to measure understanding. Similar to other studies, comprehension was not assessed before the DB was implemented. We used self-assessment during the test–retest phase. Because the scores in the retest phase were higher, this corroborated a better understanding of the content.
In summary, the authors believe that the lupus nephritis DB is a tool that is understandable to patients with different levels of education, and could potentially improve the quality of time spent in medical consultations. Despite the limitations discussed herein, this study is one more contribution to the emerging process of shared decision making, although there remains a number of questions to be addressed by future studies. To encourage other researchers to translate and adapt this DB into other languages and cultures, the Portuguese version of this DB is available by request from the lead author and can be modified and adapted to other languages and cultures. The lupus nephritis DB has been shown to be a reproducible and valid tool.