Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Community based diabetes risk assessment in Ogun state, Nigeria (World Diabetes Foundation project 08-321)

Objective: The study assessed the risk of developing type 2 diabetes Mellitus in Ogun State, Nigeria. Materials and Methods: Finnish Medical Association diabetes risk score was administered across 25 communities facilitated by non-communicable disease clinics established under a World Diabetes Foundation project. Subjects in the high risk group had blood glucose estimated. Results: 58,567 respondents included 34,990 (59.6%) females and 23,667 (40.3%) males. Majority (61.2%) were between 25 years and 54 years. Considering waist circumference, 34,990 (38.1%) females and 23,667 (5.3%) males had values above 88 cm and 102 cm respectively. Overall, 11,266 (19.2%) were obese and 28.9% overweight using body mass index (BMI). More females had elevated BMI than males. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of all subjects were 129.54 mm Hg ± 23.5 mm Hg and 76.21 mm Hg ± 15.5 mm Hg respectively. Prevalence of hypertension (Joint National Committee VII classification) was 27.7%. More subjects had normal DBP than SBP (68.2% vs. 42.5% P < 0.05). Mean fasting blood glucose (FBG) of all subjects was 5.5 mmol/L ± 0.67 mmol/L. Using a casual blood glucose >11.1 mmol/L and/or FBG >7 mmol/L, the total yield of subjects adjudged as having diabetes was 2,956 (5.05%). Mean total risk score was 5.60 ± 3.90; this was significantly higher in females (6.34 ± 4.16 vs. 4.24 ± 3.71, P < 0.05). A total of 2,956 (5.05%) had high risk of developing DM within 10 years. Conclusion: The risk of developing DM is high in the community studied with females having a higher risk score. There is urgent need to implement diabetes prevention strategies

Methods for specifying the target difference in a randomised controlled trial: the Difference ELicitation in TriAls (DELTA) systematic review

Background Randomised controlled trials (RCTs) are widely accepted as the preferred study design for evaluating healthcare interventions. When the sample size is determined, a (target) difference is typically specified that the RCT is designed to detect. This provides reassurance that the study will be informative, i.e., should such a difference exist, it is likely to be detected with the required statistical precision. The aim of this review was to identify potential methods for specifying the target difference in an RCT sample size calculation. Methods and Findings A comprehensive systematic review of medical and non-medical literature was carried out for methods that could be used to specify the target difference for an RCT sample size calculation. The databases searched were MEDLINE, MEDLINE In-Process, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, the Education Resources Information Center (ERIC), and Scopus (for in-press publications); the search period was from 1966 or the earliest date covered, to between November 2010 and January 2011. Additionally, textbooks addressing the methodology of clinical trials and International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) tripartite guidelines for clinical trials were also consulted. A narrative synthesis of methods was produced. Studies that described a method that could be used for specifying an important and/or realistic difference were included. The search identified 11,485 potentially relevant articles from the databases searched. Of these, 1,434 were selected for full-text assessment, and a further nine were identified from other sources. Fifteen clinical trial textbooks and the ICH tripartite guidelines were also reviewed. In total, 777 studies were included, and within them, seven methods were identified—anchor, distribution, health economic, opinion-seeking, pilot study, review of the evidence base, and standardised effect size. Conclusions A variety of methods are available that researchers can use for specifying the target difference in an RCT sample size calculation. Appropriate methods may vary depending on the aim (e.g., specifying an important difference versus a realistic difference), context (e.g., research question and availability of data), and underlying framework adopted (e.g., Bayesian versus conventional statistical approach). Guidance on the use of each method is given. No single method provides a perfect solution for all contexts

Assessing methods to specify the target difference for a randomised controlled trial:DELTA (Difference ELicitation in TriAls) review

Background: The randomised controlled trial (RCT) is widely considered to be the gold standard study for comparing the effectiveness of health interventions. Central to the design and validity of a RCT is a calculation of the number of participants needed (the sample size). The value used to determine the sample size can be considered the 'target difference'. From both a scientific and an ethical standpoint, selecting an appropriate target difference is of crucial importance. Determination of the target difference, as opposed to statistical approaches to calculating the sample size, has been greatly neglected though a variety of approaches have been proposed the current state of the evidence is unclear. Objectives: The aim was to provide an overview of the current evidence regarding specifying the target difference in a RCT sample size calculation. The specific objectives were to conduct a systematic review of methods for specifying a target difference; to evaluate current practice by surveying triallists; to develop guidance on specifying the target difference in a RCT; and to identify future research needs. Design: The biomedical and social science databases searched were MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register, PsycINFO, Science Citation Index, EconLit, Education Resources Information Center (ERIC) and Scopus for in-press publications. All were searched from 1966 or the earliest date of the database coverage and searches were undertaken between November 2010 and January 2011. There were three interlinked components: (1) systematic review of methods for specifying a target difference for RCTs - a comprehensive search strategy involving an electronic literature search of biomedical and some non-biomedical databases and clinical trials textbooks was carried out; (2) identification of current trial practice using two surveys of triallists - members of the Society for Clinical Trials (SCT) were invited to complete an online survey and respondents were asked about their awareness and use of, and willingness to recommend, methods; one individual per triallist group [UK Clinical Research Collaboration (UKCRC)-registered Clinical Trials Units (CTUs), Medical Research Council (MRC) UK Hubs for Trials Methodology Research and National Institute for Health Research (NIHR) UK Research Design Services (RDS)] was invited to complete a survey; (3) production of a structured guidance document to aid the design of future trials - the draft guidance was developed utilising the results of the systematic review and surveys by the project steering and advisory groups. Setting: Methodological review incorporating electronic searches, review of books and guidelines, two surveys of experts (membership of an international society and UK- and Ireland-based triallists) and development of guidance. Participants: The two surveys were sent out to membership of the SCT and UK- and Ireland-based triallists. Interventions: The review focused on methods for specifying the target difference in a RCT. It was not restricted to any type of intervention or condition. Main outcome measures: Methods for specifying the target difference for a RCT were considered. Results: The search identified 11, 485 potentially relevant studies. In total, 1434 were selected for full-text assessment and 777 were included in the review. Seven methods to specify the target difference for a RCT were identified - anchor, distribution, health economic, opinion-seeking, pilot study, review of evidence base (RoEB) and standardised effect size (SES) - each having important variations in implementation. A total of 216 of the included studies used more than one method. A total of 180 (15%) responses to the SCT survey were received, representing 13 countries. Awareness of methods ranged from 38% (n =69) for the health economic method to 90% (n =162) for the pilot study. Of the 61 surveys sent out to UK triallist groups, 34 (56%) responses were received. Awareness ranged from 97% (n =33) for the RoEB and pilot study methods to only 41% (n =14) for the distribution method. Based on the most recent trial, all bar three groups (91%, n =30) used a formal method. Guidance was developed on the use of each method and the reporting of the sample size calculation in a trial protocol and results paper. Conclusions: There is a clear need for greater use of formal methods to determine the target difference and better reporting of its specification. Raising the standard of RCT sample size calculations and the corresponding reporting of them would aid health professionals, patients, researchers and funders in judging the strength of the evidence and ensuring better use of scarce resources. Funding: The Medical Research Council UK and the National Institute for Health Research Joint Methodology Research programme

Contraceptive awareness among men in Bangladesh

Objective: A considerable gap exists between contraceptive awareness and use. Traditional approaches to measuring awareness are inadequate to properly understand the linkages between awareness and use. The objective of this study was to examine the degree of men's modern contraceptive awareness in Bangladesh and the associated determinants and further testing of a hypothesis that current contraceptive use confers a high degree of method awareness.Methods: This study used the couple data set from the Bangladesh Demographic and Health Survey (1999–2000). A two-level, multinomial logistic regression was used with the degree of contraceptive awareness as the dependent variable. The degree of awareness was measured by the reported number of modern contraceptive methods known among men aged 15–59 years. Men's responses on method awareness were classified according to those reported spontaneously and probed.Results: Nearly 100% of the study participants reported having heard of at least one method and about half reported awareness of at least eight different methods of contraception. Multinomial logistic regression analyses showed that older and educated men were more likely to have reported a high degree of awareness. The findings confirmed our hypothesis that current contraceptive use is likely to confer a high degree of modern method awareness among men (p&lt;0.001), after controlling for other important characteristics.Conclusions: Men who had a low degree of contraceptive awareness seem not properly informed of the wide range of contraceptive options. It is imperative that family planning intervention strategies in Bangladesh should focus on the degree and functional knowledge of contraceptive methods to improve the uptake of especially male-based modern methods

Assessment of the value of the methods.

<p>Assessment of the value of the methods.</p

Main variations in implementation of the methods.

<p>RCI, reliable change index; VAS, visual analogue scale; WTP, willingness to pay per unit of effectiveness.</p

Usage of methods—examples and key implementation points.

<p>IVF, in vitro fertilisation.</p