Comparative Effectiveness Review

Objective:  We conducted a systematic literature review of clinical trials to assess the comparative effectiveness of treatments for fibromyalgia in subgroups of highly affected or clinically complex adults. We focused on patient subgroups rather than overall treatment effects to complement a large systematic review being conducted on fibromyalgia treatments at McMaster University. 

Data sources:  We searched Medline®, Embase®, PsycINFO®, AMED, and the Cochrane Central Register of Controlled Trials (CENTRAL) plus reference lists of included studies and recent systematic reviews. 

Methods: Two investigators screened abstracts of identified references for eligibility (enrolled adults with fibromyalgia, examined treatment effects, had a control group, and assessed outcomes at least 3 months after treatment initiation). Full-text articles were reviewed to identify outcomes reporting for at least one adult subgroup: women, older or obese adults, individuals with coexisting mental health conditions, high severity or longer fibromyalgia duration, multiple medical comorbidities, or other chronic pain conditions. Primary outcomes included pain, symptom improvement, function, fatigue, sleep quality, participation, and health-related quality of life. We extracted data, assessed risk of bias of individual studies, and evaluated strength of evidence for each comparison and outcome. 

Results: We identified 22 randomized controlled trials (RCTs), 8 pooled analyses of patientlevel RCT data, and 4 observational studies that met inclusion criteria; 59 percent were drug trials. Adults with fibromyalgia and major depressive disorder (MDD) were studied most often; drug studies also reported outcomes by age, sex, race, and anxiety. Most drug trials examined duloxetine effects on pain and global improvement; trial duration was typically 3 months. Lowstrength evidence for duloxetine suggests that subgroups of adults with fibromyalgia and MDD do not experience differential short-term treatment effects. Other subgroup evidence is largely insufficient. For nearly all comparisons, treatment-by-subgroup interactions were not significant. Most interaction results were reported in text; only two RCTs and five pooled RCT analyses displayed data on subgroup outcomes. Losses to followup were considerable; dropout reporting was not subgroup specific. Adverse effects were reported for the MDD subgroup in one duloxetine pooled analysis; these were similar to overall adverse effects. Studies were not powered to detect subgroup effects. 

Conclusion: Despite the prevalent belief that fibromyalgia treatments may behave differently in subgroups, evidence to date is largely insufficient for fibromyalgia subgroup effects of interventions other than duloxetine in adults with concomitant MDD. Future studies should be designed to support subgroup analysis to improve clinical applicability.

Objective. We conducted a systematic review to examine the long-term consequences of discontinuing disease-modifying treatment (DMT) for multiple sclerosis (MS) by examining the long-term benefits and harms, and the reasons for discontinuing treatment. We also examined the evidence for people’s values, beliefs, and preferences regarding discontinuing DMT.   

Methods. Two investigators screened abstracts and full texts of identified references for eligibility. Eligible studies included studies of over 3 years that examined Food and Drug Administration–approved DMTs compared with placebo, other active DMT, or no DMT for adults with clinically isolated syndrome or MS in outpatient settings for patient-centered outcomes. We excluded studies of mitoxantrone, since it has a maximum lifetime dosage. Timing was relaxed for women who were considering pregnancy or already pregnant or patients discontinuing natalizumab due to risk factor changes. We extracted data, assessed risk of bias of individual studies, and evaluated strength of the body of evidence for each comparison and outcome. We also evaluated, using Technical Brief methods, studies of any design that examined individuals’ attitudes, values, and preferences for discontinuing treatments and health states, or factors and processes patients with MS and clinicians use in shared decisionmaking. 

Results. We identified 27 unique studies with discontinuation information: 16 of these contained complete information to allow full analysis of long-term benefits and harms. Evidence was insufficient for long-term benefits of DMTs for secondary progressive MS patients and most outcomes for relapsing-remitting MS (RRMS) patients. Low-strength evidence suggests higher long-term all-cause survival for treatment-naïve RRMS patients who did not delay starting interferon beta-1b by 2 years and used DMTs for a longer duration than for those who started later. Low-strength evidence suggests that interferon did not change RRMS patients’ disability progression. Limited low-strength evidence suggests that long-term harms do not differ from short-term harms. The majority of discontinuation tends to occur within 2 to 3 years. Another 25 unique studies provided intrapersonal, interpersonal, and shared decisionmaking information. No study directly asked why people may be reluctant to discontinue when treatment no longer seems effective; taken as a whole, the literature set provides some insight. The preferences literature underscores the complexity of the topic and the processes underlying decisionmaking. 

 Conclusions. MS patients and providers have little information to guide decisions to discontinue DMT.  

Objective. To summarize the effects of long-term osteoporosis drug treatment (ODT) and ODT discontinuation and holidays on fractures and harms. 

Objective. To summarize evidence on: (1) the accuracy of brief cognitive tests for identifying clinical Alzheimer’s-type dementia (CATD) in individuals with suspected cognitive impairment; (2) the accuracy of biomarkers for identifying Alzheimer’s disease (AD) in individuals with dementia; and (3) the benefits and harms of prescription drugs and supplements for cognition, function, and behavioral and psychological symptoms of dementia (BPSD) in patients with CATD.