© 2006 American Public Health Association DOI: 10.2105/AJPH.2003.036343
At the time this work was completed, Paige Muellerleile was with the Department of Psychology, University of WisconsinMarshfield, Marshfield, and Brian Mullen was with Department of Psychology, Syracuse University, Syracuse, New York. Correspondence: Requests for reprints should be sent to Paige Muellerleile, PhD, University of Wisconsin-Marshfield, 2000 West Fifth Street, Marshfield, Wisconsin 54449 (e-mail: pmueller{at}uwc.edu).
We propose cumulative meta-analysis as the procedure of completing a new meta-analysis at each successive wave in a research database. Two facets of cumulative knowledge are considered: the first, sufficiency, refers to whether the meta-analytic database adequately demonstrates that a public health intervention works. The second, stability, refers to the shifts over time in the accruing evidence about whether a public health intervention works. We used a hypothetical data set to develop the indicators of sufficiency and stability, and then applied them to existing, published datasets. Our discussion centers on the implications of the use of this procedure in evaluating public health interventions.
Meta-analysis is the statistical integration of the results of independent studies.14 This approach to the quantitative review of the weight of evidence has proven to be useful in helping determine the effectiveness of public health interventions. Meta-analysis has been used to gauge the effectiveness of interventions aimed at changing patient behavior,57 interventions aimed at changing physician behavior,8 and interventions aimed at more far-reaching public health policy.9 Traditional meta-analysis can inform public health interventions and policies, usually to determine whether an intervention has an impact on health practices, and the magnitude of that impact. However, traditional meta-analysis overlooks 2 aspects of public health information. The first is sufficiency. Sufficiency refers to whether the meta-analytic database adequately demonstrates whether a public health intervention works. For example, 1 meta-analysis10 synthesizes the relationship between socioeconomic status and self-esteem, integrating the results of 446 hypothesis tests conducted among 312 940 participants. This number of hypothesis tests begs the question of whether there was sufficient justification for using valuable research and participant resources to conduct the 446th hypothesis test to help establish the relationship between socioeconomic status and self-esteem. If there was little value in adding the 446th hypothesis test, was there sufficient value in the 445th test? What about the 200th test?11 For many public health issues, collecting additional evidence for an already-established effect may waste more than research and participant resources: delaying implementation of effective risk-reduction interventions may also waste health care resources, employer costs, and lives. The second of the aspects overlooked by traditional meta-analysis is stability. Stability refers to the shifts over time in the accruing evidence about whether a public health intervention works. For example, the purported effects of sex education have been controversial. Studies of the efficacy of sex education programs have rendered conflicting estimates of the effects of these programs on adolescent sexual activity: some studies indicate that sex education programs decrease sexual activity.12 Others indicate that sex education programs do not appear to influence rates of sexual activity.13 Still others indicate that sex education programs lead to increased sexual activity.14 As additional studies are added, the estimate of the typical effect of sex education programs on adolescent sexual activity may continue to fluctuate.15 For a number of public health issues, implementing effective interventions is a worthwhile effort. However, implementing ineffective interventions can waste health care resources, employer costs, and lives. We describe these 2 aspects of cumulative knowledge in the public health context. We discuss previous efforts to interpret cumulative meta-analysis, explain indicators of sufficiency and stability to aid interpretation of cumulative meta-analysis, and consider the use of the indicators of sufficiency and stability in a set of previously published meta-analyses.
Cumulative meta-analysis refers to the process of performing new meta-analyses at successive points in time in a research domain.16 Therefore, at each "wave" of the database (each time a study is added), a separate meta-analysis is conducted. For simplicity, all of the examples in this paper are assumed to conform to usual standards for performing an informative meta-analysis. These standards involve thorough literature searches using well-defined criteria for a specific hypothesis, and consideration of the methodological soundness of the studies to be included. They also involve careful and consistent extraction of precise tests of significance and effect size. Comprehensive discussions of standards for performing meta-analyses can be found in several sources.14,17,18
To illustrate the examination of evidence for sufficiency and stability in cumulative meta-analysis, we will make use of a hypothetical data set that has previously been used to illustrate other meta-analytic issues.1,2,16,19,20 Table 1
Initially, assessment of the evidence for sufficiency and stability comes from visual examination of the results of a cumulative meta-analysis. Figure 1a Fisher 2 = 0.42. Performing a new meta-analysis for each of the 10 waves in the database results in a mean effect size of Fisher 10 = 0.50.
The 95% confidence intervals (CIs) around each Fisher i are not intended for use as estimators of inferential probabilities. Cumulative meta-analysis necessarily involves multiple tests of the same hypothesis, and using CIs for estimating inferential probabilities therefore increases the likelihood of committing a Type I error. In this context, rather than being indications of the likelihood that the effects are significant, the CIs indicate the range of values that are statistically equivalent to the parameter. In other words, the CIi around the Fisher i for wave i indicates the range of values indistinguishable from the parameter value. Generally, the CIis become narrower as the number of hypothesis tests, ki, increases, and as the cumulative sample size, Ni, increases.19 For a Fisher i that remains constant, then, additional studies result in narrower CIi s around that mean, which decreases the range of values for the effect size that are statistically equivalent to the true effect size.
From the first wave through the end of the database, the evidence for the effect of X on Y appeared to be sufficient: the CIi around the mean effect size did not include the value of zero. Put differently, the range of values for the mean effect size at each wave appeared to be statistically different from a null effect. Therefore, it would be hard to argue for additional research about the effects of X on Y, as it appears that the effect was there from the start. Similarly, from the first wave through the end of the database, the evidence for the effect of X on Y appeared to be stable: there is little change in the value of the mean effect. Therefore, it would be hard to argue for additional research to determine whether the emergent picture of the effect of X upon Y might change. Although the visual information presented in Figure 1a
Previous meta-analytic undertakings2326 have not differentiated sufficiency from stability; however, both sufficiency and stability are implied in these efforts. For example, Lau and others24 observed that there was sufficient evidence for researchers to have shown intravenous streptokinase for acute infarction to be a lifesaving therapy 25 years before its approval by the Food and Drug Administration. Likewise, they noted that 2 additional clinical trials did not change the value of the therapy established by the preceding evidence. Nevertheless, previous efforts to interpret cumulative meta-analyses were based on a visual inspection of the accumulating results, similar to the foregoing discussion of results portrayed in Figure 1 Pogue and Yusuf25 suggested a different approach for determining when accumulating evidence is statistically significant, which involves the adaptation of classical monitoring boundaries. They propose that the cumulative meta-analyst calculate an "optimum information size," which is the cumulative sample size needed to demonstrate an effect, in light of event rates and the minimum reasonable values of the independent variable that would be considered consequential. Although their efforts to produce a method for statistical inference within cumulative meta-analysis are commendable, there has been little debate about the efficacy of the proposed monitoring boundaries. We propose the use of more straightforward indicators of sufficiency and stability, even though there may not be accompanying inferential probabilities for them. The first reason for using more straightforward indicators is their simplicity. The second reason for using more straightforward indicators is that Pogue and Yusuf25 require a priori specification of the optimum information size. However, a researcher must know what the event rates might bewhich requires an understanding of what minimum effects of the independent variable are both consequential and reasonablebefore specifying the optimum information size. In other words, the researcher would need extensive knowledge of the observed results of the accumulated research before undertaking a cumulative meta-analysis to understand the observed results of the accumulated research. Finally, the third reason for using more straightforward indicators is that Pogue and Yusuf were concerned only with sufficiency: whether additional evidence is needed to establish that X has some effect upon Y. They did not address whether that effect has become stable across waves in a database.25 For these reasons, we propose that cumulative meta-analysts make use of more straightforward indicators of (both) sufficiency and stability.
The indicators we propose rely on inspection of graphs of a type of meta-analytic "time-series" data.16 Some researchers have argued there is little agreement among judges who interpret visual information,27,28 which may result in different conclusions about those data than conclusions on the basis of statistical analysis.2931 However, a meta-analysis on the subject of visual interpretation of data showed that interjudge agreement can be quite good.32 Moreover, other scholars have recommended guidelines for creation of graphical presentations that facilitate interjudge agreement (e.g., consistent axes and scaling).3341 Following such guidelines, we hope to reduce the potential for lack of agreement among judges.
Clearly, the hypothetical database presented in Table 1
The Failsafe Ratio
Rosenthal47 noted that it would be unlikely that there would be 5 times as many unretrieved studies as there were in the meta-analysts database. He proposed that Nfs(P = 0.05) exceed 5k + 10 (the addition of 10 studies would ensure that for very small meta-analytic databases of 1 or 2 studies, the number of unretrieved studies would be 15 or 20, rather than only 5 or 10). The importance of the failsafe number Nfs(P = 0.05) and Rosenthals47 5k + 10 standard is illustrated by the studies that use it.4852 The "failsafe ratio" is an indicator of the relative sizes of the failsafe number and the Rosenthal standard, and is calculated as follows:
where ki = the number of studies in the database at wave i. If the failsafe ratio is less than 1.000, then Nfs(P = 0.05)i at wave i has not exceeded the 5ki + 10 standard. Thus, the results at wave i are still vulnerable to future null results. If the failsafe ratio exceeds 1.000, then Nfs(P = 0.05)i at wave i has exceeded the 5ki + 10 standard. Thus, the results at wave i will tolerate future null results.
Figure 1b
Because the value of the failsafe ratio is less than 1.000, the results at wave 1 are still vulnerable to future null results. The second wave added 1 study (k2 = 2), and the Nfs(P = 0.05) 2 = 20.7. Therefore, the value of the failsafe ratio would be:
Because the failsafe ratio exceeds 1.000, the results at wave 2 are likely to tolerate future null results. The value of the failsafe ratio continues to increase to a value of 10.483 by the 10th wave of the database.
Inspection of the failsafe ratio displayed in Figure 1b Although the failsafe ratio can indicate the sufficiency of a research database, it does not adequately address the stability of the effect size. To the extent that the results of additional studies are of different magnitudes (as long as they are not null effects, on average), there can be fluctuations in the magnitude of the cumulative effect size that will not be captured by examination of the failsafe ratio. It is necessary to consider a more direct indicator of stability.
The Cumulative Slope
Additionally, the regression line in Figure 1c
Figure 1c
Inspection of the slopes displayed in Figure 1d Examining sufficiency and stability as complementary aspects of an emerging cumulative meta-analytic database allow the analyst to consider the separate contributions that sufficiency and stability can make toward understanding the phenomenon. In the case of a phenomenon that appears to be strong at the outset, a cumulative slope of 0.000 indicates that additional studies would continue to support the phenomenons existence (high sufficiency). However, in the case of a phenomenon that appears to be negligible or null at the outset, a cumulative slope of 0.000 suggests that additional studies would not support existence of the phenomenon (low sufficiency). As such, the cumulative slope is a better indicator of the stability of a phenomenon than of sufficient evidence for it.
Summary
A selection of meta-analyses published in the public health literature can illustrate the application of these indicators of sufficiency and stability. Selection of the following 4 meta-analyses was on the basis of 2 factors: they attempted to evaluate the effectiveness of a particular public health intervention, and they used compatible meta-analytic techniques. The selection includes McArthurs55 integration of a school-based intervention on heart-healthy eating behaviors, White and Pitts56 integration of drug education interventions to reducing drug use, Koger et al.s57 integration of music therapy interventions for increasing skills among adults with dementia, and Acton and Kangs58 integration of interventions to reduce burden among caregivers for adults with dementia. By happenstance, 2 of these datasets address issues for youth,55,56 and 2 datasets address issues for older adults.57,58 Table 2
Figure 2
Examination of Figure 2b
A third picture emerges from examination of Figure 2c
Finally, the picture that emerges in Figure 2d
We have proposed the failsafe ratio as an indicator of sufficiency, and the cumulative slope as an indicator of stability. The indicators illustrate the complementary nature of the sufficiency and stability aspects of cumulative knowledge in the hypothetical data set presented in Table 1 The complementary aspects of cumulative knowledge, sufficiency and stability, correspond with 2 dimensions of study outcome: significance level and effect size. First, significance level refers to the likelihood of having obtained the observed results, or results more extreme, if in fact the null hypothesis of no difference is true, whereas sufficiency refers to whether the cumulative weight of evidence allows us to accept the existence of the phenomenon. Sufficiency requires a high cumulative probability. Second, effect size refers to the strength of a phenomenon, whereas stability refers to whether the cumulative weight of evidence has leveled off at a steady aggregate picture of the phenomenon. Stability requires a steady cumulative average effect. The cumulative meta-analytic context underscores the role of the size of the database. At the individual study level, significance levels and effect sizes are linked through the size of the sample. That is, a significant effect of P = 0.0499999 might be weak if based on a large sample (n = 1000, ZFisher = 0.052), but strong if based on a small sample (n = 3, ZFisher = 1.830).4 Given the correspondence between significance level/effect size and sufficiency/stability, the size of the database should play a pivotal role in cumulative meta-analysis. Indeed, this appears to be the point of Schmidts20 admonition: when is it possible to tell when there is sufficient evidence for the existence of a phenomenon?
The implications for using cumulative meta-analysis are varied. Among its possible uses are changing school curricula, changing recommendations for physicians, assessing research goals, or modifying criteria for funding research. Although cumulative meta-analysis cannot take the place of other considerations that inform decision-making practice, it is an additional tool that policy makers can use to make better decisions about implementing programs. The cumulative meta-analysis generated from the integration of heart-healthy nutrition interventions55 demonstrated that, early on, both sufficiency and stability for an effective program was attained. However, the cumulative meta-analysis generated from the integration of drug abuse prevention programs56 demonstrated that sufficiency was never established, but stability for the essentially null effect was established by the fourth wave in the database. However, these 2 programs appear to receive differential research support and commitment. For example, the Healthy People 2010 59 guidelines delineate only 1 objective for improving nutrition in school meals, but there are at least 7 objectives for decreasing substance use among schoolchildren. Although drug abuse is a serious public health problem, the Healthy People 2010 objectives appear to be made on the basis of some of the same studies that appeared in White and Pitts meta-analysis,56 indicating an overemphasis on promoting programs from which schoolchildren derive no benefit. Meanwhile, the objectives underemphasize a program from which schoolchildren derive significant benefits. Despite the emerging cultural alarm over obesity and its associated health problems, efficacious heart-healthy eating programs appear to be overlooked. Indeed, a simple MEDLINE search of the literature on schoolchildren corroborates this suspicion: A search for heart healthy and nutrition yielded 13 citations; a search for drug abuse and prevention yielded 651 citations. The rendered wisdom from current research objectives is that there is more promotion of (ineffective) drug abuse prevention programs than (effective) heart-healthy eating programs. Consider the cumulative meta-analysis generated from the integration58 of interventions to reduce caregiver burden. The cumulative meta-analysis demonstrated that by the seventh wave in the database, stability for the negligible effect was attained, indicating no substantive changes to the accruing evidence that interventions do not reduce caregiver burden. However, 7 years after stability was established, 1 study60 set out recommendations for physicians to identify and intervene with overburdened caregivers. Their recommendations included the same educational, counseling, and respite-care services assessed in the primary-level studies integrated in Acton and Kangs58 meta-analysis. Moreover, 8 years after stability for the negligible effect was attained, the US Department of Health and Human Services61 issued a preliminary report on governmental commitments to programs for independent living, including caregiver burden reduction programs. The report claims that "a growing body of evidence confirms that the provision of supportive services can diminish caregiver burden, [and] permit caregivers to remain in the workforce. . . ."61 The 2001 appropriations for the National Caregiver Support Program were $125 000 000.61 To date, we have been unable to determine that any appropriations have been dedicated for music therapy programs. The rendered wisdom from current research objectives is that there is more promotion of (ineffective) caregiver burden reduction programs than (effective) music therapy programs. The examples above make it clear that research in public health can benefit from tools for determining when sufficient evidence has accrued to establish intervention efficacy. There are several valuable applications of this approach. For example, for research questions involving moderators, cumulative meta-analysis can be used to examine sufficiency and stability separately within levels of the moderator: The evidence from studies testing the intervention at 1 level of the moderator may demonstrate sufficiency, whereas studies testing another level of the moderator may not demonstrate sufficiency. Similarly, cumulative meta-analysis can be used to gauge the fit of public policy recommendations: despite the evidence that the effect of caregiver burden reduction levels off at zero, policy recommendations favor more funding. Finally, this approach may provide an empirically based benchmark against which funding proposals can be evaluated by granting agencies: proposals for new studies that use cumulative meta-analysis to document that current evidence for an intervention that has not yet achieved stability stand as particularly valuable opportunities to invest time, effort, and resources. The failsafe ratio and cumulative slope can reveal information about an emerging phenomenon to help researchers make the best use of limited resources needed to advance the state of the science and improve public health.
Peer Reviewed
Contributors
Human Participant Protection Accepted for publication January 5, 2005.
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