A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

Propensity score analysis with partially observed covariates: How should multiple imputation be used?

Inverse probability of treatment weighting is a popular propensity score-based approach to estimate marginal treatment effects in observational studies at risk of confounding bias. A major issue when estimating the propensity score is the presence of partially observed covariates. Multiple imputation is a natural approach to handle missing data on covariates: covariates are imputed and a propensity score analysis is performed in each imputed dataset to estimate the treatment effect. The treatment effect estimates from each imputed dataset are then combined to obtain an overall estimate. We call this method MIte. However, an alternative approach has been proposed, in which the propensity scores are combined across the imputed datasets (MIps). Therefore, there are remaining uncertainties about how to implement multiple imputation for propensity score analysis: (a) should we apply Rubin's rules to the inverse probability of treatment weighting treatment effect estimates or to the propensity score estimates themselves? (b) does the outcome have to be included in the imputation model? (c) how should we estimate the variance of the inverse probability of treatment weighting estimator after multiple imputation? We studied the consistency and balancing properties of the MIte and MIps estimators and performed a simulation study to empirically assess their performance for the analysis of a binary outcome. We also compared the performance of these methods to complete case analysis and the missingness pattern approach, which uses a different propensity score model for each pattern of missingness, and a third multiple imputation approach in which the propensity score parameters are combined rather than the propensity scores themselves (MIpar). Under a missing at random mechanism, complete case and missingness pattern analyses were biased in most cases for estimating the marginal treatment effect, whereas multiple imputation approaches were approximately unbiased as long as the outcome was included in the imputation model. Only MIte was unbiased in all the studied scenarios and Rubin's rules provided good variance estimates for MIte. The propensity score estimated in the MIte approach showed good balancing properties. In conclusion, when using multiple imputation in the inverse probability of treatment weighting context, MIte with the outcome included in the imputation model is the preferred approach

Sabotage in Contests: A Survey

A contest is a situation in which individuals expend irretrievable resources to win valuable prize(s). ‘Sabotage’ is a deliberate and costly act of damaging a rival’s' likelihood of winning the contest. Sabotage can be observed in, e.g., sports, war, promotion tournaments, political or marketing campaigns. In this article, we provide a model and various perspectives on such sabotage activities and review the economics literature analyzing the act of sabotage in contests. We discuss the theories and evidence highlighting the means of sabotage, why sabotage occurs, and the effects of sabotage on individual players and on overall welfare, along with possible mechanisms to reduce sabotage. We note that most sabotage activities are aimed at the ablest player, the possibility of sabotage reduces productive effort exerted by the players, and sabotage may lessen the effectiveness of public policies, such as affirmative action, or information revelation in contests. We discuss various policies that a designer may employ to counteract sabotage activities. We conclude by pointing out some areas of future research

Anharmonicity, vibrational instability and Boson peak in glasses

We show that a {\em vibrational instability} of the spectrum of weakly interacting quasi-local harmonic modes creates the maximum in the inelastic scattering intensity in glasses, the Boson peak. The instability, limited by anharmonicity, causes a complete reconstruction of the vibrational density of states (DOS) below some frequency $\omega_c$, proportional to the strength of interaction. The DOS of the new {\em harmonic modes} is independent of the actual value of the anharmonicity. It is a universal function of frequency depending on a single parameter -- the Boson peak frequency, $\omega_b$ which is a function of interaction strength. The excess of the DOS over the Debye value is $\propto\omega^4$ at low frequencies and linear in $\omega$ in the interval $\omega_b \ll \omega \ll \omega_c$. Our results are in an excellent agreement with recent experimental studies.Comment: LaTeX, 8 pages, 6 figure

The likelihood of extinction of iconic and dominant herbivores and detritivores of coral reefs: the parrotfishes and surgeonfishes

Parrotfishes and surgeonfishes perform important functional roles in the dynamics of coral reef systems. This is a consequence of their varied feeding behaviors ranging from targeted consumption of living plant material (primarily surgeonfishes) to feeding on detrital aggregates that are either scraped from the reef surface or excavated from the deeper reef substratum (primarily parrotfishes). Increased fishing pressure and widespread habitat destruction have led to population declines for several species of these two groups. Species-specific data on global distribution, population status, life history characteristics, and major threats were compiled for each of the 179 known species of parrotfishes and surgeonfishes to determine the likelihood of extinction of each species under the Categories and Criteria of the IUCN Red List of Threatened Species. Due in part to the extensive distributions of most species and the life history traits exhibited in these two families, only three (1.7%) of the species are listed at an elevated risk of global extinction. The majority of the parrotfishes and surgeonfishes (86%) are listed as Least Concern, 10% are listed as Data Deficient and 1% are listed as Near Threatened. The risk of localized extinction, however, is higher in some areas, particularly in the Coral Triangle region. The relatively low proportion of species globally listed in threatened Categories is highly encouraging, and some conservation successes are attributed to concentrated conservation efforts. However, with the growing realization of man's profound impact on the planet, conservation actions such as improved marine reserve networks, more stringent fishing regulations, and continued monitoring of the population status at the species and community levels are imperative for the prevention of species loss in these groups of important and iconic coral reef fishes

The roles of herbal remedies in survival and quality of life among long-term breast cancer survivors - results of a prospective study

<p>Abstract</p> <p>Background</p> <p>Few data exist on survival or health-related quality of life (QOL) related to herbal remedy use among long-term breast cancer survivors. The objective of this report is to examine whether herbal remedy use is associated with survival or the health-related QOL of these long-term breast cancer survivors.</p> <p>Methods</p> <p>In 1999-2000, we collected the information of herbal remedy use and QOL during a telephone interview with 371 Los Angeles Non-Hispanic/Hispanic white women who had survived more than 10 years after breast cancer diagnosis. QOL was measured using the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. Patients were followed for mortality from the baseline interview through 2007. 299 surviving patients completed a second telephone interview on QOL in 2002-2004. We used multivariable Cox proportional hazards methods to estimate relative risks (RR) and 95% confidence intervals (CI) for mortality and applied multivariable linear regression models to compare average SF-36 change scores (follow-up - baseline) between herbal remedy users and non-users.</p> <p>Results</p> <p>Fifty-nine percent of participants were herbal remedy users at baseline. The most commonly used herbal remedies were echinacea, herbal teas, and ginko biloba. Herbal remedy use was associated with non-statistically significant increases in the risks for all-cause (44 deaths, RR = 1.28, 95% CI = 0.62-2.64) and breast cancer (33 deaths, RR = 1.78, 95% CI = 0.72-4.40) mortality. Both herbal remedy users' and non-users' mental component summary scores on the SF-36 increased similarly from the first survey to the second survey (<it>P </it>= 0.16), but herbal remedy users' physical component summary scores decreased more than those of non-users (-5.7 vs. -3.2, <it>P </it>= 0.02).</p> <p>Conclusions</p> <p>Our data provide some evidence that herbal remedy use is associated with poorer survival and a poorer physical component score for health-related QOL among women who have survived breast cancer for at least 10 years. These conclusions are based on exploratory analyses of data from a prospective study using two-sided statistical tests with no correction for multiple testing and are limited by few deaths for mortality analysis and lack of information on when herbal remedy use was initiated or duration of or reasons for use.</p