Depending on perspective, different expert panels, professional organizations, or individual physicians may use different cut points of overall strength of evidence in formulating therapeutic guidelines or in taking action; however, a formal description of the level of evidence provides a uniform framework for the data, leading to specific recommendations.The PDQ Adult Treatment Editorial Board and the PDQ Pediatric Treatment Editorial Board add information on levels of evidence, described below, to the PDQ Adult Cancer Treatment Summaries and the PDQ Pediatric Cancer Treatment Summaries when appropriate.Nevertheless, it is rational in many circumstances to use a treatment that improves these surrogate endpoints while awaiting a more definitive endpoint to support its use.Because studies or clinical experiences are ranked both by strength of design and importance of endpoint, a given study would have a two-tiered ranking (e.g., 1ii A for a nonblinded randomized study showing a favorable outcome in overall survival and 3iii Div for a phase II trial of selected patients with response rate as the outcome).Meta-analyses of randomized studies offer a quantitative synthesis of previously conducted studies.The strength of evidence from a meta-analysis is based on the quality of the conduct of individual studies.Outcomes of the large, randomized, controlled trials were not predicted accurately by the meta-analysis 35% of the time.[1,2] Meta-analyses performed by different investigators to address the same clinical issue can reach contradictory conclusions. Therefore, meta-analyses of randomized studies are placed in the same category of strength of evidence as are randomized studies, not at a higher level.Subset analyses of randomized studies are subject to errors inherent in multiplicity (i.e., statistically significant results to be expected as a result of random variation of measured effects in multiple subsets).
Revised text to include nonconsecutive cases or other observational study designs (e.g., cohort or case-control studies).
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available.
This section describes the latest changes made to this summary as of the date above.
These clinical experiences are the weakest form of study design, but they may be the only available or practical information in support of a therapeutic strategy, especially in the case of rare diseases or when the evolution of the therapy predates the common use of randomized study designs in medical practice.
They may also provide the only practical design when treatments in study arms are radically different (e.g., amputation vs. Nevertheless, they always raise issues of patient selection and comparability with other populations.
These endpoints may be subject to investigator interpretation.
More importantly, they may, but do not automatically, translate into direct patient benefit such as survival or quality of life.
In addition, all recommendations must take into account other issues that cannot be so easily quantified, such as toxicity, width of confidence intervals of observations, trial size, quality assurance in the trial, and cost.
Nevertheless, the PDQ ranking system provides an ordinal categorization of strength of evidence as a starting point for discussions of study results.
In most cases, however, it should be possible to blind the investigator and the patient until the randomization has been made.
If blinding of the therapy delivered cannot be accomplished, a rank of 1ii is assigned.