Levels of Evidence for Supportive and Palliative Care Studies (PDQ®): Supportive care - Health Professional Information [NCI]

Introduction

The PDQ supportive and palliative care information summaries provide descriptions of the pathophysiology and treatment of common physical and psychosocial complications of cancer and its treatment, including complications such as pain, anxiety, depression, fatigue, and nausea and vomiting. Each PDQ health professional summary generally includes an overview; information about etiology, assessment, and management; and citations to published literature.

The supportive and palliative care of cancer patients and their families and caregivers can involve the identification and mitigation of physiological, psychological, and spiritual needs.

1. Physiological complications currently addressed in the PDQ supportive and palliative care summaries include the following:
   • Cardiopulmonary syndromes.
   • Temperature fluctuation.
   • Gastrointestinal complications.
   • Metabolic disorders.
   • Lymphedema.
   • Nausea and vomiting.
   • Oral complications.
   • Pain.
   • Dermatological problems.
   • Sexual dysfunction.
   • Sleep abnormalities.
   • Malnutrition.
   • Dehydration.
   • Fatigue.
   • Cachexia.
   • Weight loss/weight gain.
2. Psychological or behavioral complications currently addressed in the PDQ supportive and palliative care summaries include the following:
   • Anxiety.
   • Cognitive disorders.
   • Depression.
   • Grief issues.
   • Adjustment difficulties.
   • Post-traumatic stress disorder.
   • Tobacco dependence/smoking cessation.
   • Nutrition/weight management.
   • Substance abuse.
3. Spiritual and religious concerns currently addressed in the PDQ supportive and palliative care summaries include the following:
   • Spiritual experience.
   • Religious beliefs.
   • Approaches to addressing these issues.

References cited in the PDQ supportive and palliative care information summaries are drawn primarily from the peer-reviewed biomedical literature. The quality and reliability of such published reports can vary considerably. To help readers assess the strength of findings from clinical research studies, levels-of-evidence rankings are often employed. These rankings generally take into account the strength of a study's design and the strength of the clinical outcome(s) measured. Clinical research in supportive and palliative care is feasible in some settings but difficult to conduct in others, such as at the end of life. Furthermore, as in other areas of medicine, supportive and palliative care decisions must be made in the context of existing evidence, which may be weaker than ideal.

In general, the quality of evidence depends on:

• The appropriateness of the study to the question being asked.
• How well the study was designed, implemented, analyzed, and interpreted.

For evaluating outcomes of both medical and psychosocial interventions, the strongest evidence is obtained from well-designed, well-conducted randomized clinical trials. For evaluating other questions, particularly those related to symptom management, well-designed descriptive studies may provide the strongest evidence practicable. Particular elements of study design, such as the nature of the population being studied or the duration of observation, may be crucial to assessing the quality of a study. Reviews of studies will indicate the level of evidence and any confounding design issues.

During the early phases of research in a new area, information relevant to the needs of patients and clinicians may come from a limited number of reports and data of varying strength. This information may include evidence from:

• Well-designed prospective studies (e.g., randomized trials, nonrandomized trials, cohort studies, and case series).
• Cross-sectional studies (e.g., correlational designs using various levels of analytic sophistication).
• Retrospective studies (e.g., case-control studies, case series, and case reports).

The studies may be interventional, may be observational, or may involve provider or patient self-reports or record reviews.

In some cases, the best available evidence may reflect clinical/professional experience or expert consensus opinion. All sources may yield information relevant to patients and clinicians, who may be required to make management decisions before the best possible evidence is available.

In view of this complexity, the PDQ Supportive and Palliative Care Editorial Board took a pragmatic approach to defining the levels of evidence that it would utilize. The levels used by the Board focus primarily on the strength of a study's design as appropriate to the questions being investigated. These levels should be easily understood by health professionals and serve as a starting point for discussing the strength of study results.

Study Design Categories, Definitions, and Levels of Evidence

1. Prospective, randomized, controlled trials and meta-analyses of prospective, randomized, controlled trials.

   The randomized, double-blinded, controlled trial is the gold standard of study design. To achieve this ranking, the study allocation must be blinded to the investigator both before and after the randomization and the assignment to intervention group. This design provides protection from allocation bias by the investigator and from bias in the assessment of outcomes by both the investigator and the patient.

   Unfortunately, double-blinding after intervention assignment is not always possible because procedures or side effects often vary substantially among study interventions in ways that are obvious to both the investigator and the patient. In some cases, however, it should be possible to blind the investigator and the patient until the randomization has been made, even if intervention delivery cannot be blinded. Furthermore, randomized trials are still subject to imbalances if sample size is inadequate to the question of interest, and may be less than optimal owing to other design elements such as choice of sample, measurement approach, appropriateness of the comparison condition, or loss to follow-up.

   Meta-analysis of randomized studies offers a quantitative synthesis of previously conducted studies. The strength of the evidence from a meta-analysis is based on the quality of the individual studies included. Moreover, meta-analyses can magnify small systematic errors in individual studies.

   Because the results of meta-analyses and the randomized trials upon which they are based do not always agree and because meta-analyses performed by different investigators to address the same issue can reach contradictory conclusions, meta-analyses of randomized studies are placed in the same category of strength of evidence as are randomized studies, not at a higher level.

2. Prospective, nonrandomized, controlled trials; prospective cohort studies; prospective case series; and cross-sectional studies.

   In nonrandomized controlled trials, allocation to intervention group is made on the basis of:

   • Birth date.
   • Chart number.
   • Bed availability.
   • Day of clinic appointment.
   • Any other strategy known to the investigator before informed consent is obtained from the patient.

   Imbalances can occur in intervention allocations under such circumstances but can also be taken into account statistically.

   A prospective cohort study is a longitudinal study in which a defined group of individuals who share a certain condition and/or who are exposed to a particular intervention are followed over time and compared with another group of individuals who are not exposed to the intervention under study. The general population from which the cohort is drawn or another cohort can be used as the comparison group. Alternatively, subgroups within a cohort can be compared with each other.

   A prospective case series is an uncontrolled study involving either consecutive cases or nonconsecutive cases. Although the evidence from this type of study is weaker than that from a controlled study, this design may be the only one practical in certain settings. Evidence from a consecutive case series is considered stronger than that from a nonconsecutive case series, and population-based series drawn from a well-defined population are stronger than non-population-based series.

   Cross-sectional/correlational studies are widely used to investigate the relationship among variables in one or more groups of individuals. Depending on the research question, they may be the highest level of design possible and may even be the most appropriate to examine the relationships among multiple variables. Analytic strategies, including multivariate approaches, need to be matched to the question at issue. A combination of cross-sectional and longitudinal data collection can be explored with very sophisticated path analytic approaches, with the imputation of causality. Quality can nevertheless vary considerably, depending on:

   • Choice of measurement.
   • Adequacy of sample size.
   • Representativeness of sample.
   • Quality of statistical analysis.
3. Retrospective studies.

   Retrospective studies include:

   • Case-control studies.
   • Retrospective case studies.
   • Individual case reports.

   In case-control studies, two groups of individuals-one with a disease or condition (cases) and a similar group without the disease or condition (controls)-are compared. The cases should be representative of all cases in a population but do not have to include all cases in a population. The controls should come from the same population as the cases.

   Retrospective studies are prone to numerous biases, including selection bias and lack of information about confounding variables from medical records or memories of the study participants (recall bias). Incident cases are preferable to prevalent cases to help reduce bias.

   Evidence obtained from retrospective studies, especially case reports, is among the weakest forms of evidence. However, systematic qualitative research, while often retrospective in nature, improves substantially on anecdotal case reports.

4. Opinions of respected authorities based on clinical experience, consensus statements from expert committees, or authoritative reviews.

   The evidence supporting conclusions or recommendations in opinions, consensus statements, or authoritative reviews can be highly variable and subject to important biases. This category of evidence is usually considered the lowest in many levels-of-evidence rankings.

Changes to This Summary (06 / 17 / 2015)

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.

Editorial changes were made to this summary.

This summary is written and maintained by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the formal ranking system used by the PDQ Editorial Boards to assess evidence supporting the use of specific interventions or approaches. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Supportive and Palliative Care Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Supportive and Palliative Care Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."

The preferred citation for this PDQ summary is:

PDQ® Supportive and Palliative Care Editorial Board. PDQ Levels of Evidence for Supportive and Palliative Care Studies. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/publications/pdq/levels-evidence/supportive-care. Accessed <MM/DD/YYYY>. [PMID: 26389413]

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Last Revised: 2015-06-17