Although fatigue is a common symptom, it is also one that is vague, imprecise, and nonspecific. One of the essential problems in the study and measurement of fatigue, either as a singular entity or as a component of a more well-defined disorder, is the failure to differentiate various types of fatigue.
In Chronic Fatigue and Its Syndromes (Wessely et al. 1998), the authors challenge the reader to try a “thought experiment” that clearly illustrates the dilemma encountered in defining and assessing fatigue.
Below, their experiment has been expanded and modified; however, the message regarding the problems encountered in defining fatigue remains intact.
• You run 5 miles under adverse conditions; even before starting you feel weak and daunted at the prospect. After completing only a portion of the course, you stop; the next day you are sore and tired.
• You are asked to carefully check the references for a 600-page book on fatigue. You feel overwhelmed and really just want to ride your bike. After a few hours your eyes hurt, you are weary, your concentration diminishes, and you are making many mistakes.
• It’s flu season and you are feeling achy and weak. Your nose is running, your throat is sore, and all you want to do is go to bed.
• You have just been up for two days finishing a grant proposal, then had to take a “red eye” and deliver the application in person to make the grant deadline.
• You have been driving in your car for an hour. The landscape is boring and you can hardly keep your eyes open. All you want to do is sleep. You also often feel like this when at home watching TV.
• Climbing stairs has become progressively, though subtly, more difficult over the last two years.
• Although at first, exertion is not bothersome, after 10–15 minutes, you experience constant cramping in your extremities.
These examples illustrate the multidimensionality of fatigue. Fatigue can occur in anticipation of a task and be influenced by both physical (e.g., the length of the run) and psychological factors (e.g., how rewarding it will be). Fatigue can also be interpreted as a sense of effort needed to perform a task, and both physical and mental tasks may result in fatigue.
In conjunction with the sensation or perception of fatigue, the effort associated with a task may be manifested as a change in behavior, especially a decrement in performance (e.g., information processing declines when one feels tired). Fatigue is also most often acute, and in such cases typically resolves after completion of the task.
In cases in which fatigue is more chronic and pervasive, it is frequently associated with illness, stress, and sleep disturbances.
Finally, as the last two vignettes illustrate, fatigue must be distinguished from sleepiness or drowsiness and true muscle weakness since these symptoms are associated with a different array of conditions, usually primary sleep and muscle disorders.
Thus, it is clear that a simple question regarding “fatigue” is not likely to be very informative or precise. Yet elements of fatigue can be ascertained if care is taken in questioning an individual or in constructing an instrument. However, complicating matters even more is the fact that patients often have additional meanings for fatigue.
Sometimes, the word fatigue is used as a synonym for other complaints while at other times it becomes a general term to encompass an array of symptoms that occur together.
Patients will often equate fatigue with weakness, dizziness, lack of coordination or stamina, feeling “spacey,”poor concentration/cognitive abilities, having “rubber legs,” boredom, lack of motivation, malaise, or feeling blue or depressed.
Despite the further ambiguity introduced by these descriptors, it is clear that fatigue has distinct physical and mental aspects that must be considered in measurement.
Copyright © National Academy of Sciences. All rights reserved.
I
n this report, conditions of unknown etiology for which treatments are examined include chronic fatigue syndrome (fatigue, headache, cognitive dysfunction, and other symptoms), depression (fatigue, loss of memory and other general symptoms, cognitive dysfunction, and sleep disturbances), fibromyalgia (muscle pain, sleep disturbances, fatigue), and irritable bowel syndrome (diarrhea, constipation, abdominal pain, nausea, vomiting, and other gastrointestinal symptoms). Other diagnoses such as headache and panic disorder are included in the report because they involve symptoms similar to those reported by Gulf War veterans.
Evidence of symptoms is self-report
Treatment efficacy is the benefit produced by a given treatment in tightly controlled, perhaps artificial, study conditions in which patients are carefully selected and may be more frequently observed, tested, and monitored than is typically the case in routine practice.
A number of study designs can provide varying levels of evidence of treatment efficacy. They include, from strongest to weakest: conditions in which patients are carefully selected and may be more frequently observed, tested, and monitored than is typically the case in routine practice. A number of study designs can provide varying levels of evidence of treatment efficacy.
They include, from strongest to weakest:
• Multiple well-designed randomized controlled trials (RCTs);
• Single well-designed RCTs or multiple small RCTs;
• Cohort study, particularly one with “multiple on/off” features;
• Case-control study; and
• Series of clinical observations or anecdotes.
(My Comments: This where most of the ME/CFS clinicians observations, treatment protocols and anecdotal information is obtained. It is considered at the low end for consideration for treatment efficacy for ME/CFS patients)
In addition to the above designs, there is the technique of meta-analysis. Meta-analysis was developed to fit the situation in which study results are not fully consistent or there are multiple studies of differing degrees of design rigor. In meta-analysis the results of multiple studies are combined to yield an overall cross-study estimate of effectiveness.
In its review of clinical studies, the U.S. Preventive Health ServicesTask Force (USPHSTF) used strict criteria for selecting admissible evidence of effectiveness in grading the
quality of evidence (see Table ES-1).
The task force gave greater weight to those study designs that, for methodological
reasons, are less subject to bias and inferential error (USPHSTF 1996).
In evaluating treatments for Gulf War veterans, the committee
TABLE ES-1 Quality of Evidence
Level Evidence
I Evidence obtained from at least one properly randomized controlled trial.
(CBT/ GET PACE ?)
II-1 Evidence obtained from well-designed controlled trials without randomization.
II-2 Evidence obtained from well-designed cohort or case-control analytical studies, preferably from more than one center or research group.
II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.
III Opinions of respected authorities, based on clinical experience, descriptive studies, and case reports, or reports of expert committees.
(ME/CFS Clinicians)
Treatment
effectiveness studies, including the largest and most comprehensive outcomes studies, emphasize external validity often at the expense of internal validity. They may involve very large samples that are fully representative of the patients seen in routine clinical practice, but the studies may include confounding factors that weaken the inferences about cause-and-effect relationships.
The committee believes the results of a single, well-designed outcomes study (e.g., a cohort study or variation of care and outcome study) should be considered to be as compelling as the results of a single, well controlled randomized trial in determining treatment
effectiveness.
An outcomes study will have few concerns about the generalizability of its findings to real-world settings (external validity) but perhaps some concerns about internal validity; RCTs will have the opposite pattern of
T
he randomized controlled trial (RCT) is the most reliable methodology for assessing the efficacy of treatments in medicine. In such a trial a defined group of study patients is assigned to either receive the treatment or not, or to receive different doses of the treatment, through a formal process of randomization.
TABLE 3-1 Hierarchy of Evidence
Emphasis on Efficacy Emphasis on Effectiveness (My Comments: Determination base on this critieria and selecting the top critieria as being the best treatment option after reviewing research papers on clinical trial treatments)
Level I Systematic Review (e.g., meta- Systematic Review (e.g., meta analysis) of Several Well-Controlled analysis) of Several Well-Randomized Trials—consistent results Designed Outcome Studies or “Effectiveness RCTs”—consistent results
(CBT/ GET PACE ?)
Level II Single, Well-Controlled Single, Well-Designed Randomized Trial Outcomes Study or
“Effectiveness RCT”
Level III Consistent Findings from Multiple Cohort, Case-Control, or Observational Studies*
Level IV Single Cohort, Case-Control, or Observational Study
(ME/CFS Clinicians)
Level V Uncontrolled Experiment, Unsystematic Observation, Expert Opinion
(ME/CFS Clinicians)
Document Attached
This is probably very close to the analysis that ME/CFS IOM Panel will generate using this as a basis for selection and establishing treatment protocols: This involves not only Chronic Fatigue Syndrome but Neurological (cognitive dysfunction, loss of memory, and sleep disturbances), irritable bowel syndrome (diarrhea, constipation, abdominal pain, nausea, vomiting, and other gastrointestinal symptoms),fibromyalgia (muscle pain, sleep disturbances, fatigue)
Eco