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Deficient reporting and interpretation of non-inferiority randomized clinical trials in HIV patients: a systematic review.

Hernandez AV, Pasupuleti V, Deshpande A, Thota P, Collins JA, Vidal JE - PLoS ONE (2013)

Bottom Line: We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established.Of the 42 RCTs (n = 21,919; range 41-3,316) selected, 23 were in ARV-naïve and 19 in ARV-experienced patients.Twenty-seven (64%) RCTs provided information about prior RCTs of the active comparator, and 37 (88%) used 2-sided CIs.

View Article: PubMed Central - PubMed

Affiliation: Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.

ABSTRACT

Objectives: Non-inferiority (NI) randomized clinical trials (RCTs) commonly evaluate efficacy of new antiretroviral (ARV) drugs in human immunodeficiency virus (HIV) patients. Their reporting and interpretation have not been systematically evaluated. We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established.

Design: Systematic review.

Methods: PubMed, Web of Science, and Scopus were reviewed until December 2011. Selection and extraction was performed independently by three reviewers.

Results: Of the 42 RCTs (n = 21,919; range 41-3,316) selected, 23 were in ARV-naïve and 19 in ARV-experienced patients. Twenty-seven (64%) RCTs provided information about prior RCTs of the active comparator, and 37 (88%) used 2-sided CIs. Two thirds of trials used a NI margin between 10 and 12%, although only 12 explained the method to determine it. Blinding was used in 9 studies only. The main conclusion was based on both intention-to-treat (ITT) and per protocol (PP) analyses in 5 trials, on PP analysis only in 4 studies, and on ITT only in 31 studies. Eleven of 16 studies with NI inconclusive or not established highlighted NI or equivalence, and distracted readers with positive secondary results.

Conclusions: There is poor reporting and interpretation of NI RCTs performed in HIV patients. Maximizing the reporting of the method of NI margin determination, use of blinding and both ITT and PP analyses, and interpreting negative NI according to actual primary findings will improve the understanding of results and their translation into clinical practice.

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pone-0063272-g001: Search strategy profile of the systematic review.

Mentions: Of the 109 citations retrieved and screened, 63 articles were identified and assessed for eligibility (Figure 1). Forty-two NI trials in HIV patients were selected from criteria described above and Table 1 and Table 2 summarize the main characteristics of trials in ARV-naïve and ARV-experienced patients, respectively. Of the 42 RCTs (n = 21,919; range 41–3,316) selected, 23 were in ARV-naïve [11]–[33] and 19 in ARV-experienced [34]–[52] patients. The earliest NI trial was published in the year 2000. The funding source for majority of the studies was pharmaceutical companies (alone or with a nonprofit source); 19 (83%) and 11 (58%) studies in ARV-naïve and ARV-experienced HIV patients, respectively. Government funding was the next most common source of funding; 4 (17%) and 7 (37%) studies in ARV-naïve and ARV-experienced HIV patients, respectively. Duration of the trials ranged from 16 weeks to 4.9 years. Primary outcomes were clearly identified in all NI trials, and the most common primary endpoint was the proportion of patients with HIV RNA levels <50 copies/mL.


Deficient reporting and interpretation of non-inferiority randomized clinical trials in HIV patients: a systematic review.

Hernandez AV, Pasupuleti V, Deshpande A, Thota P, Collins JA, Vidal JE - PLoS ONE (2013)

Search strategy profile of the systematic review.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643946&req=5

pone-0063272-g001: Search strategy profile of the systematic review.
Mentions: Of the 109 citations retrieved and screened, 63 articles were identified and assessed for eligibility (Figure 1). Forty-two NI trials in HIV patients were selected from criteria described above and Table 1 and Table 2 summarize the main characteristics of trials in ARV-naïve and ARV-experienced patients, respectively. Of the 42 RCTs (n = 21,919; range 41–3,316) selected, 23 were in ARV-naïve [11]–[33] and 19 in ARV-experienced [34]–[52] patients. The earliest NI trial was published in the year 2000. The funding source for majority of the studies was pharmaceutical companies (alone or with a nonprofit source); 19 (83%) and 11 (58%) studies in ARV-naïve and ARV-experienced HIV patients, respectively. Government funding was the next most common source of funding; 4 (17%) and 7 (37%) studies in ARV-naïve and ARV-experienced HIV patients, respectively. Duration of the trials ranged from 16 weeks to 4.9 years. Primary outcomes were clearly identified in all NI trials, and the most common primary endpoint was the proportion of patients with HIV RNA levels <50 copies/mL.

Bottom Line: We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established.Of the 42 RCTs (n = 21,919; range 41-3,316) selected, 23 were in ARV-naïve and 19 in ARV-experienced patients.Twenty-seven (64%) RCTs provided information about prior RCTs of the active comparator, and 37 (88%) used 2-sided CIs.

View Article: PubMed Central - PubMed

Affiliation: Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.

ABSTRACT

Objectives: Non-inferiority (NI) randomized clinical trials (RCTs) commonly evaluate efficacy of new antiretroviral (ARV) drugs in human immunodeficiency virus (HIV) patients. Their reporting and interpretation have not been systematically evaluated. We evaluated the reporting of NI RCTs in HIV patients according to the CONSORT statement and assessed the degree of misinterpretation of RCTs when NI was inconclusive or not established.

Design: Systematic review.

Methods: PubMed, Web of Science, and Scopus were reviewed until December 2011. Selection and extraction was performed independently by three reviewers.

Results: Of the 42 RCTs (n = 21,919; range 41-3,316) selected, 23 were in ARV-naïve and 19 in ARV-experienced patients. Twenty-seven (64%) RCTs provided information about prior RCTs of the active comparator, and 37 (88%) used 2-sided CIs. Two thirds of trials used a NI margin between 10 and 12%, although only 12 explained the method to determine it. Blinding was used in 9 studies only. The main conclusion was based on both intention-to-treat (ITT) and per protocol (PP) analyses in 5 trials, on PP analysis only in 4 studies, and on ITT only in 31 studies. Eleven of 16 studies with NI inconclusive or not established highlighted NI or equivalence, and distracted readers with positive secondary results.

Conclusions: There is poor reporting and interpretation of NI RCTs performed in HIV patients. Maximizing the reporting of the method of NI margin determination, use of blinding and both ITT and PP analyses, and interpreting negative NI according to actual primary findings will improve the understanding of results and their translation into clinical practice.

Show MeSH
Related in: MedlinePlus