Last observation carried forward analysis

Very often, a last-observation-carried-forward analysis is carried out in which the last available observation in any patient is used. 

Adverse events were recorded throughout the study. In the population in Ref. [1], treatment success after 8weeks was achieved by 14% of subjects in the calcipotriol foam group versus 7% of subjects in the vehicle foam group. In the last-observation-carried-forward analysis, treatment success was achieved by more subjects with calcipotriene foam than with vehicle foam (15% vs 7%). In study 2, treatment success was achieved by more subjects in the calcipotriene foam group for the primary end point (27% vs 16%) and the LOCF analysis (28% vs 16%). Subjects in the calcipotriene foam group exhibited better response rates than did the vehicle foam group for most of the secondary outcomes. 

Key Concepts for Creating Analysis Data Sets 84 Defining Variables Once 84 Defining Study Populations 85 Defining Baseline Observations 85 Last Observation Carried Forward (LOCF) 86 Defining Study Day 89 Windowing Data 91 Transposing Data 94... 

Clinical assessments were made by specialized raters not involved in the treatment after 1, 4, 8, 12 and 16 weeks. The study was intended to include 96 patients, 15 of whom withdrew at the very beginning when they heard what treatment they were to be given. Most of those withdrawing were in the psychotherapy group. In addition, patients who failed to show any pronounced improvement in their symptoms within 8 weeks or whose condition even deteriorated were withdrawn from the study. In the case of those patients withdrawing from the study, scores recorded at the time of withdrawal were used for purposes of evaluation this represents a last observation carried forward (LOCF) analysis. Withdrawals from the study occurred rather frequently and showed the following distribution ... 

In either case, reaching this point indicates that the drug is beneficial or not and is at least a qualitative endpoint. Last observation carried forward (LOCF), a standard method of data analysis, carries the last data point forward week by week. Random regression models can estimate what would happen at a later time point, assuming that patients change in a linear fashion. Improvement, however, often levels off. Thus, creating data points based on questionable assumptions can potentially introduce substantial bias. 

An international, multicenter, double-blind trial addressed the acute efficacy and safety of a single-dose range of olanzapine (5 to 20 mg/day) compared with a single-dose range of haloperidol (5 to 20 mg/day) (11.6). A total of 1996 patients with a DSM-lll-R diagnosis of schizophrenia (83.1%), schizophreniform disorder (1.9%), or schizoaffective disorder (15%) participated in this study. The primary overall efficacy analysis (i.e., the difference in baseline to endpoint (last observation carried forward [LOCF]) mean change on the BPRS) found olanzapine to be statistically superior to haloperidol (HPDL) (i.e., -10.98 -7.93 p < 0.015). 

For example, in the analgesic example cited above (25), a comparison was made between an analysis using the last observation carried forward (LOCF) method and the proposed mixed effects maximum likelihood method. Although this was a retrospective analysis, similar contrasts could be included in the trial s simulation to ascertain the most appropriate analytical methodology to include in the study design (protocol). Other analysis factors for consideration include appropriate correction of variability, where such sources may include differences between sites or regional differences. 

Last observation carried forward (LOCF) analysis is the standard approach with a... 

Carpenter J, Kenward M, Evans S, White I (2004) Last observation carry-forward and iast observation analysis. Statistics in Medicine 23 3241-3242 author repiy 3242-3244. 

It is usually required to perform an intent-to-treat analysis that will include data on all patients who were enrolled and began treatment, regardless of whether they followed protocol, finished the study, violated protocol, or dropped out.The purpose here is to ensure the safety of the investigational substance, because substantial bias would be built into the overall analysis with the exclusion of patients who could not tolerate medication and dropped out, or who were not helped by the medication and switched to another treatment. In addition, of course, there might be an analysis of the results from all patients who followed the entire protocol properly.The intent-to-treat analysis should include patients who withdrew from the study the last clinical measurements taken for these patients should be carried forward as the last observation or final score—the so-called end point analysis. 

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