What term describes the fda’s behavior in this situation?

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What to measure. In order to assess whether dieting is an effective treatment for overweight and obesity, we must first decide on appropriate criteria upon which to judge it. The MAPP refers to this criterion as the primary endpoint, and for dieting, this endpoint is nearly always weight loss. Although we would argue that improved health rather than weight loss should be the measure of effectiveness, we recognize that weight loss is the currently accepted definition of success. We therefore summarize how FDA Phase 2 criteria would be applied when evaluating the effectiveness of dieting in reducing weight.

The necessary amount of weight loss for a diet to be considered effective is somewhat arbitrary, and it has changed dramatically since researchers first started routinely studied dieting. The original standard for success required dieters to reach a “normal” weight as defined by the Metropolitan Life Insurance Company (1942). For example, an average height woman (5′5′′) of medium body frame was expected to weigh about 134 pounds (Metropolitan Life Insurance Company, 1942), so a 200-pound woman of average height would need to lose 66 pounds to be considered a successful dieter. This standard was rarely achieved (Stunkard and McLaren-Hume, 1959), and over the next 50 years the standard changed from losing 20% of one’s starting weight, to 10%, and to just 5% of one’s starting weight (Institute of Medicine, 1995, p. 5). Now, an average height woman weighing 200 pounds needs to lose just 10 pounds to be considered a successful dieter. The use of this criterion as the primary endpoint would need to be justified to the FDA in terms of its validity and whether it provides “a reasonable assessment of clinical benefit” (Center for Drug Evaluation and Research, 2010).

When to measure it. In addition to selecting an appropriate endpoint, researchers also need to decide when that endpoint should be assessed. The current standard set by the Institute of Medicine is that individuals need to maintain a 5% weight loss for a year. The year, however, is counted as beginning when the diet begins, rather than beginning when that target weight is reached. This convention is likely used to make it easier to evaluate and compare diets, because individuals reach target weights at different time-points. Regardless, the 1 year weight loss maintenance standard is not actually a measure of whether one maintained weight loss for a full year, but rather whether an individual is at the target weight 1 year after beginning the diet. The MAPP requires a discussion of the “adequacy of duration” of the clinical trials, and it is not clear if this maintenance period would be considered adequate.

The issue of when to judge the success of a treatment is particularly complex when it comes to dieting. Dieters tend to take off weight quickly at first, then more slowly, followed by weight regain over several more years (Garner and Wooley, 1991). The effectiveness of the diet will look quite different if it is measured at the end of the early stage when weight has come off, or later, as it is regained.

Pharmaceutical treatments differ on whether they are evaluated during active treatment or at some time point after treatment ends. An antibiotic would not be considered effective if the bacteria were only eradicated during the time individuals were taking the medication, and then came back again after the treatment ended. Similarly, chemotherapy for cancer would not be judged effective if tumors reappeared immediately at the end of treatment. On the other hand, medications such as anti-depressants and pain medications are only expected to be effective while individuals are taking them.

It can be argued that diets are only expected to “work” while individuals are actively engaging in them. If so, then the short-term effectiveness would be considered the appropriate measure. Proponents of this viewpoint argue that diets would work if individuals would just stay on them, and the short-term effectiveness is the only measure taken while individuals are still restricting their intake. It is not yet known, however, if diets stop leading to weight loss because individuals stop restricting their eating, or if individuals stop restricting their eating because the diets stopped leading to weight loss (or a combination of these). There is evidence that dieters’ weight loss tends to level off during diets even while they adhere to the diet (Tataranni and Ravussin, 2004), and that individuals who successfully lose weight at a certain calorie level cannot necessarily maintain the new weight at that calorie level (Leibel and Hirsch, 1984). If this is the case, then dieters should be informed that they can only expect their diet to work for a somewhat brief length of time. This is not a unique circumstance. For example, extended use of medications such as alprazolam (Xanax) and diazepam (Valium) can result in medication tolerance (i.e., requiring higher doses to achieve the same effect; Ellinwood et al., 1985), and these anxiety medications are usually explicitly recommended for short-term use. Another consideration is whether the use of dieting treatment might make subsequent dieting treatments less effective (Tataranni and Ravussin, 2004), just as cochlear implants can render other treatments for hearing loss impossible (Lenarz et al., 2013).

In terms of evaluating the effectiveness of diets, we are proponents of the viewpoint that one cannot consider a diet successful if individuals rapidly regain the weight they lost. According to this viewpoint, the longer-term effectiveness is the appropriate measure. Obesity-related illnesses tend to be chronic diseases, such as cardiovascular disease and diabetes, and to be successful, we believe their treatments must lead to long-term benefits.

Study design. In addition to describing the outcomes of the clinical trials, the MAPP also requires a discussion of aspects of study design that might limit the conclusions that can be drawn. One area of focus is whether the validity of the study is threatened by “subject disposition,” which includes both the rate of subject exclusion from entry into the study and the rate of drop-outs.

Generalizability can be threatened when the exclusion criteria for a study are so extensive that the sample is not representative of typical users of that drug. In dieting studies, participants can be excluded if their BMI is above a certain cut-off, they have a present or past diagnosis of heart disease, angina, or other physical or psychological illnesses, or if their levels of certain macro-or micro-nutrients (e.g., glucose, sodium) are too high (reviewed in Tomiyama et al., 2013). These exclusions limit the generalizability of the findings to just healthier dieters. Of more concern in terms of generalizability, several studies exclude subjects that researchers felt would not be able to adhere to the study requirements. These multiple enrollment steps, called “run-in periods,” are often recommended in clinical trials and are intentionally stringent in order to isolate a participant pool that will remain in the study until the end (Friedman et al., 2010). This may result in samples of participants who are more motivated and more successful at altering their behavior than the average dieter. In one study, for example, 18.8% of the potential participants were excluded before the study began for failing to control their diabetes with their diet for the previous 6 weeks (Hanefeld et al., 1991).

Generalizability can also be threatened due to study attrition (for a more detailed analysis of this problem, see Mann et al., 2007). Many reasons for loss to follow-up are seemingly random (e.g., the subject moves and can no longer be located by the researchers). Others could be problematic (e.g., excluding subjects from analyses because of serious illness or death). To the extent that these drop-outs occur in differing proportions among the diet and control conditions, internal validity may also be threatened.

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