Anthony Harris

A randomized, controlled trial of early versus late initiation of dialysis

BACKGROUND In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease. METHODS We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m2 of body-surface area (calculated with the use of the Cockcroft-Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause. RESULTS Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P=0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis). CONCLUSIONS In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.)

Cost-Effectiveness Analysis and the Consistency of Decision Making: Evidence from Pharmaceutical Reimbursement in Australia (1991 to 1996)

AbstractObjective: The principle aim of this study was to generate a league table of drugs considered by the Australian Pharmaceutical Benefits Advisory Committee (PBAC) for reimbursement. The table was used to test the hypothesis that decisions made by the PBAC are consistent with the maxim of economic efficiency. In addition, we explored whether the past decisions by the PBAC revealed a threshold incremental cost-effectiveness ratio beyond which the PBAC is not prepared to recommend reimbursement of a drug. Methods: All 355 submissions made to the PBAC between January 1991 and June 1996 were reviewed. Submissions using cost per life-year gained (26 submissions) or the cost per quality adjusted life-year (QALY) gained (9 submissions) were ranked in a league table and compared with advice given by the PBAC about that drug. The confidentiality restrictions for the submissions require that the individual drug details cannot be revealed in this article. Results: There was a statistically significant difference between the cost per life-year gained for drugs that were recommended for listing and those that were not, suggesting that the PBAC has been broadly consistent with the use of economic efficiency as a criterion for decision making. We did not find an explicit threshold beyond which the PBAC was unwilling to pay for additional life years gained. However, between 1992 and 1996 the PBAC appears to have been unlikely to recommend a drug for listing if the additional cost per life-year exceeded 76 000 Australian dollars [

Lateral wedge insoles for medial knee osteoarthritis: 12 month randomised controlled trial

AU] (1998/1999 values) and was unlikely to reject a drug for which the additional cost per life-year gained was less than

The role of value for money in public insurance coverage decisions for drugs in Australia: a retrospective analysis 1994-2004

AU42 000. The cost-effectiveness ratio was not the only factor determining the reimbursement decision. Conclusions: The results of this preliminary study indicate that decisions to recommend a drug for listing by the PBAC in the last few years have, by and large, been consistent with the notion of economic efficiency.

Acupuncture for Chronic Knee Pain: A Randomized Clinical Trial

Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis. Design Randomised controlled trial. Setting Community in Melbourne, Australia. Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis. Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months. Main outcome measures Primary symptomatic outcome was change in overall knee pain (past week) measured on an 11 point numerical rating scale. Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans. Secondary clinical outcomes included changes in measures of pain, function, stiffness, and health related quality of life. Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions. Results Between group differences did not differ significantly for the primary outcomes of change in overall pain (−0.3 points, 95% confidence intervals −1.0 to 0.3) and change in medial tibial cartilage volume (−0.4 mm3, 95% confidence interval −15.4 to 14.6), and confidence intervals did not include minimal clinically important differences. None of the changes in secondary outcomes showed differences between groups. Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles. Trial registration Australian New Zealand Clinical Trials Registry ACTR12605000503628 and ClinicalTrials.gov NCT00415259.

Efficacy of standardised manual therapy and home exercise programme for chronic rotator cuff disease: randomised placebo controlled trial.

Objective . To analyze the relative influence of factors in decisions for public insurance coverage of new drugs in Australia. Data Sources . Evidence presented at meetings of the Australian Pharmaceutical Benefits Advisory Committee (PBAC) that makes recommendations on coverage of drugs under Pharmaceutical Benefits Scheme. Study Selection . All major submissions to the PBAC between February 1994 and December 2004 (n = 858) if one of the outcomes measured was life year gained (n=138) or quality-adjusted life years (QALYs) gained (n=116). Results . Clinical significance, cost-effectiveness, cost to government, and severity of disease were significant influences on decisions. Compared to the average submission, clinical significance increased the probability of recommending coverage by 0.21 (95% confidence interval [CI] 0.02 to 0.40), whereas a drug in a life-threatening condition had an increased probability of being recommended for coverage of 0.38 (0.06 to 0.69). An increase in

RESOURCE COSTING FOR MULTINATIONAL NEUROLOGIC CLINICAL TRIALS : METHODS AND RESULTS

A10,000 from a mean incremental cost per QALY of

Effect of Physical Therapy on Pain and Function in Patients With Hip Osteoarthritis: A Randomized Clinical Trial

A46,400 reduced the probability of listing by 0.06 (95% CI 0.04 to 0.1). Conclusions . The PBAC provides an example of the long-term stability and coherence of evidence-based coverage and pricing decisions for drugs that weighs up the evidence on clinical effectiveness, clinical need, and value for money. There is no evidence of a fixed public threshold value of life years or QALYs, but willingness to pay is clearly related to the characteristics of the clinical condition, perceived confidence in the evidence of effectiveness and its relevance, as well as total cost to government.

Cost-Effectiveness of Initiating Dialysis Early: A Randomized Controlled Trial

IMPORTANCE There is debate about benefits of acupuncture for knee pain. OBJECTIVE To determine the efficacy of laser and needle acupuncture for chronic knee pain. DESIGN, SETTING, AND PARTICIPANTS Zelen-design clinical trial (randomization occurred before informed consent), in Victoria, Australia (February 2010-December 2012). Community volunteers (282 patients aged ≥50 years with chronic knee pain) were treated by family physician acupuncturists. INTERVENTIONS No acupuncture (control group, n = 71) and needle (n = 70), laser (n = 71), and sham laser (n = 70) acupuncture. Treatments were delivered for 12 weeks. Participants and acupuncturists were blinded to laser and sham laser acupuncture. Control participants were unaware of the trial. MAIN OUTCOMES AND MEASURES Primary outcomes were average knee pain (numeric rating scale, 0 [no pain] to 10 [worst pain possible]; minimal clinically important difference [MCID], 1.8 units) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index, 0 [no difficulty] to 68 [extreme difficulty]; MCID, 6 units) at 12 weeks. Secondary outcomes included other pain and function measures, quality of life, global change, and 1-year follow-up. Analyses were by intention-to-treat using multiple imputation for missing outcome data. RESULTS At 12 weeks and 1 year, 26 (9%) and 50 (18%) participants were lost to follow-up, respectively. Analyses showed neither needle nor laser acupuncture significantly improved pain (mean difference; -0.4 units; 95% CI, -1.2 to 0.4, and -0.1; 95% CI, -0.9 to 0.7, respectively) or function (-1.7; 95% CI, -6.1 to 2.6, and 0.5; 95% CI, -3.4 to 4.4, respectively) compared with sham at 12 weeks. Compared with control, needle and laser acupuncture resulted in modest improvements in pain (-1.1; 95% CI, -1.8 to -0.4, and -0.8; 95% CI, -1.5 to -0.1, respectively) at 12 weeks, but not at 1 year. Needle acupuncture resulted in modest improvement in function compared with control at 12 weeks (-3.9; 95% CI, -7.7 to -0.2) but was not significantly different from sham (-1.7; 95% CI, -6.1 to 2.6) and was not maintained at 1 year. There were no differences for most secondary outcomes and no serious adverse events. CONCLUSIONS AND RELEVANCE In patients older than 50 years with moderate or severe chronic knee pain, neither laser nor needle acupuncture conferred benefit over sham for pain or function. Our findings do not support acupuncture for these patients. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12609001001280.

A randomised trial of the cost effectiveness of buprenorphine as an alternative to methadone maintenance treatment for heroin dependence in a primary care setting

Objective To investigate the efficacy of a programme of manual therapy and exercise treatment compared with placebo treatment delivered by physiotherapists for people with chronic rotator cuff disease. Design Randomised, participant and single assessor blinded, placebo controlled trial. Setting Metropolitan region of Melbourne, Victoria, Australia. Participants 120 participants with chronic (>3 months) rotator cuff disease recruited through medical practitioners and from the community. Interventions The active treatment comprised a manual therapy and home exercise programme; the placebo treatment comprised inactive ultrasound therapy and application of an inert gel. Participants in both groups received 10 sessions of individual standardised treatment over 10 weeks. For the following 12 weeks, the active group continued the home exercise programme and the placebo group received no treatment. Main outcome measures The primary outcomes were pain and function measured by the shoulder pain and disability index, average pain on movement measured on an 11 point numerical rating scale, and participants’ perceived global rating of overall change. Results 112 (93%) participants completed the 22 week trial. At 11 weeks no difference was found between groups for change in shoulder pain and disability index (3.6, 95% confidence interval −2.1 to 9.4) or change in pain (0.7, −0.1 to 1.5); both groups showed significant improvements. More participants in the active group reported a successful outcome (defined as “much better”), although the difference was not statistically significant: 42% (24/57) of active participants and 30% (18/61) of placebo participants (relative risk 1.43, 0.87 to 2.34). The active group showed a significantly greater improvement in shoulder pain and disability index than did the placebo group at 22 weeks (between group difference 7.1, 0.3 to 13.9), although no significant difference existed between groups for change in pain (0.9, −0.03 to 1.7) or for the percentage of participants reporting a successful treatment outcome (relative risk 1.39, 0.94 to 2.03). Several secondary outcomes favoured the active group, including shoulder pain and disability index function score, muscle strength, interference with activity, and quality of life. Conclusion A standardised programme of manual therapy and home exercise did not confer additional immediate benefits for pain and function compared with a realistic placebo treatment that controlled for therapists’ contact in middle aged to older adults with chronic rotator cuff disease. However, greater improvements were apparent at follow-up, particularly in shoulder function and strength, suggesting that benefits with active treatment take longer to manifest. Trial registration Clinical trials NCT00415441.