Non-experimental Study Designs Research Articles

Re: Impact of Human Papillomavirus (HPV)-6/11/16/18 Vaccine on All HPV-Associated Genital Diseases in Young Women

As we contemplate the astonishing successes of human papillomavirus (HPV) vaccines, it is worthwhile to consider whether randomized controlled trials of the sort recently published in the Journal can ever show reductions in cervical cancer rates (1). In their excellent article, Munoz et al. (1) reported nearly complete efficacy of quadrivalent HPV vaccine against vulvar and cervical intraepithelial neoplasia, adenocarcinoma in situ, and genital warts that contained viral types in the vaccine. Of course, this study did not show differences in cervical cancer because that was never its intent. However, the hope that one day randomized controlled trials like these will finally show that HPV vaccines prevent cervical cancer is nicely summarized by the conclusion of a recent systematic review (2) of HPV vaccine trials, “To evaluate cervical cancer incidence and mortality, a longer follow-up is necessary.” But is this really true? Assessing clinical trial outcomes related to cervical disease typically requires regular Papanicolaou test screenings, and ethics require that women with abnormal screening results receive follow-up and treatment, as appropriate. This combination of screening and treatment should prevent all but the most aggressive interval cervical cancers (3). Indeed, one of the most interesting findings reported by Munoz et al. was that none of the women in the trial developed cervical cancer during the approximately 63 000 women-years reported. Because their study participants had at least annual screening for cervical abnormalities to assess the main outcomes, clinicians treated abnormalities identified during the tests with procedures known to be effective in preventing cervical cancer and thus vastly reduced the chances the women would get cervical cancer. We can think of this risk reduction as reflecting a “cervical cancer Heisenberg principle,” according to which studying intermediate outcomes obliterates more severe ones. One way that researchers have devised to get around this Heisenbergian challenge is to design studies that continue past the duration of most efficacy trials (ie, beyond 4–6 years) (3). Women remain randomly assigned to condition, but they no longer receive regular testing as part of the trial. Instead, the researchers follow the women over the next decades by linking their identities to national cancer registries. The ethical justification is that routine screening and medical treatment outside the trial are the standard of care. In contrast, HPV vaccine provision to older women is not the standard of care, and the majority of HPV infections will have already occurred during the ages in which women were enrolled in the trial. The other alternative to get around this Heisenbergian challenge is to evaluate HPV vaccine impact at the population level by use of one of the many alternatives that we have previously reviewed elsewhere (4). These evaluations have to rely on prospective cohort studies and other nonexperimental study designs that yield weaker evidence than randomized controlled trials. One such study (5) recently reported decreases in the incidence of genital warts after implementation of a national HPV vaccination program in Australia. It is highly likely that additional studies, many of which are under way, will provide similar correlational evidence for the population-level impact of HPV vaccine on cervical cancer. While we wait for further evidence to accumulate, it is important to remember that most randomized controlled trials cannot and will not tell us whether HPV vaccines prevent cervical cancer.

Acute Migraine Treatment With Rizatriptan in Real World Settings – Focusing on Treatment Strategy, Effectiveness, and Behavior

Although randomized controlled trials (RCTs) are the gold standard for assessing efficacy of a drug intervention, because they are conducted in a highly selected group of patients, they do not necessarily reflect normal customary or optimized patient care. Accordingly, information from RCTs must be supplemented by outcomes research and by nonexperimental or quasi-experimental study designs. Herein, we discuss information that supplements the rigorous but sometimes rigid nature of RCTs in an effort to better understand the clinical utility of drug treatment for migraine with patient-centered outcomes in mind. We start by discussing several lessons we learned from RCTs on comparative triptan studies, followed by presenting data on outcomes studies for rizatriptan. We then briefly discuss migraine treatment behavior issues, including early treatment and adherence to treatment.

Smoking in Germany: Stylized Facts, Behavioral Models, and Health Policy

It is well known that smoking causes severe adverse health effects, and it seems evident that governments are justified or even obliged to implement measures of tobacco control to mitigate these effects. Yet, as this paper argues with a distinct focus on Germany, the three most important and still largely open questions in the design and implementation of economic and health policy are, whether government action is justified at all, what behavioral patterns this policy should try to alter, and whether the policy measures chosen indeed exert any substantial effects on the targeted outcomes. We conclude that the case for control measures aiming at the prevention of smoking initiation among adolescents is indeed strong, but also that their proper design would benefit from a better understanding of behavioral issues and that their empirical evaluation requires (non-experimental) study designs that facilitate the identification of causal effects.

Beyond the Randomized Clinical Trial

Randomized clinical trials (RCTs) are familiar to most clinicians involved in the care of patients with cardiovascular disease. RCTs are the uncontested “gold standard” for establishing causation between a therapy and outcomes for a compelling reason: A large randomized experiment is the only study design that can guarantee that control and intervention subjects are similar in all the known and unknown attributes that influence outcomes.1 In general, RCTs use a rigorous experimental design with the primary goal of understanding the “average” overall benefit and risk of using a standardized therapy in a selected group of patients.2 When well conducted, RCTs have internal validity, and a therapy that is found to have a net biological benefit is considered efficacious.3 Establishing the efficacy of new therapies is critical for advancing medical knowledge. Yet even when an RCT demonstrates substantial net benefit for a specific therapy, its optimal role in routine clinical practice can remain unclear. Concerns frequently relate to how well the therapy may perform in different clinical settings and in broader patient populations than those studied in traditional RCTs. In addition, it is often unclear how therapies are best applied within the larger environment of the healthcare delivery system where costs and availability become issues for patients and clinicians. These concepts, which refer to the external validity of a clinical trial,3 become important as new therapies are applied in real-world settings and are a key focus area for many studies in health services and outcomes research. In contrast to efficacy studies like traditional RCTs, effectiveness studies often require a broader range of methodological tools, which can include both experimental and nonexperimental study designs. In the present article, we review reasons why evidence from traditional RCTs must generally be supplemented by evidence from effectiveness studies to inform best …

Evaluation of community-wide interventions: the ecologic case-referent study design.

In a setting of long-standing, community-wide and generally accepted prevention activities like youth health care services in The Netherlands, evaluative research in the form of experimental studies is hardly possible. Furthermore, as most interventions will bear fruit only after several years and the effects are often described in rather vague terms, even non-experimental study designs are fraught with possible difficulties. Although a study design using aggregate data is generally considered inferior or 'incomplete', in many cases, especially in health services research, this approach can be the only one feasible to evaluate the effectiveness of preventive programmes and interventions. In this article we present the ecologic case-referent design as a potentially expedient and valid method for estimating the ecologic effect of a population-wide intervention on the outcome rate in those populations. In this case-referent design, many variables are measured at the individual level, whereas the main exposure variable is measured at an aggregate or ecologic level. Using recently published studies as an example, the advantages and drawbacks of the design are discussed using the randomised controlled trial design as the referent study design.

A continuity of care integrated literature review, Part 2: Methodological issues.

In Part 2 of this two-part series, research designs, methods, and measurement of continuity of care are explored. Qualitative, integrated literature review of a sample of 38 continuity of care nursing research article published 1990-1995. Ganong's (1987) stages of the integrative literature research review process were followed. A data collection tool was designed and pilot tested, and rules for data analysis and interpretation were established. Research articles were systematically analyzed and reported using descriptive analysis. Results showed few nursing models, primarily convenience sampling and nonexperimental cross-sectional study designs, varied data collection methods, and inadequate instrumentation. Measurement criteria were diverse and influenced by the perspectives of the measurer. Continuity of patient care was identified as a construct comprised of many related and tangential concepts in need of more sophisticated review. Recommendations for researchers are discussed.

Relation between experimental and non-experimental study designs. HB vaccines: a case study.

STUDY OBJECTIVE: To examine the relation between experimental and non-experimental study design in vaccinology. DESIGN: Assessment of each study design's capability of testing four aspects of vaccine performance, namely immunogenicity...

Family planning program effects on contraceptive use in Morocco 1992-1995.

This study illustrates the use of panel data and a fixed-effects estimator to investigate the impact of family planning program inputs on contraceptive utilization in Morocco during the 1992–1995 period. By controlling the potential bias resulting from common unobserved determinants of program resource allocation decisions and program outcomes, the methodology helps overcome an important constraint to the use of non-experimental study designs in undertaking meaningful impact assessments. Data from a panel of women interviewed in both the 1992 and 1995 Morocco Demographic and Health Surveys were used in the study, along with ‘program’ data from Service Availability Modules undertaken in conjunction with each survey round. The results indicate that changes in the family planning supply environment, in particular increased presence of nurses trained in family planning and the level of infrastructure at public clinics, played a significant role in the increased use of modern contraceptives during the study period.

Study design for technology assessment: critical issues

The epidemiological methods have become useful tools for the assessment of the effectiveness and safety of health care technologies. The experimental methods, namely the randomized controlled trials (RCT), give the best evidence of the effect of a technology. However, the ethical issues and the very nature of the intervention under study sometimes make it difficult to carry out an RCT. Therefore, quasi-experimental and non-experimental study designs are also applied. The critical issues concerning these designs are discussed. The results of evaluative studies are of importance for decision-makers in health policy. The measurements of the impact of a medical technology should go beyond a statement of its effectiveness, because the essential outcome of an intervention or programme is the health status and quality of life of the individuals and populations concerned.