General Clinical Trials

There are different types of clinical studies (Fig. 2.1). They can be divided into observational and clinical trials (interventional). Observational studies include cohort studies, in which a group of subjects are followed to analyze potential risk factors for developing a disease; case control studies, in which one group of people who have the disease of interest and another group who do not have the disease are compared to identify potential risk factors; and cross-sectional studies, in which an entire population is observed at one point in time to determine data such as disease prevalence or risks [1]. Observational studies offer helpful information regarding associations that may exist between certain exposures and outcomes. This information would be useful if a researcher is trying to determine if a group of people with a common exposure have a change in the risk of developing a certain disease [2]. For example, a case–control retrospective study by Robinson et al. sought to investigate whether the use of photosensitizing medications increased the likelihood of developing non-melanoma skin cancer. This observational study examined people who had a form of non-melanoma skin cancer (case) as well as those who did not (control), and determined how many from each group had been exposed to photosensitizing medications. The data showed that the use of photosensitizing medications may increase the risk of developing a form of non-melanoma skin cancer [3]. Because this study examined exposures from the past, it is considered a retrospective study. Studies that examine a present exposure and measure future outcomes are called prospective studies and they, too, offer useful information regarding links between exposures and outcomes [2]. Chen et al. conducted a prospective cohort observational study by identifying patients who had a non-melanoma skin cancer that was treated either by electrodessication/curettage, general excision, or Mohs excision. These patients were followed to identify any recurrences of their skin cancer in an effort to determine if any of the treatment methods was superior in terms of reduced recurrence rates. The data collected showed that the difference in recurrence rates among the treatment methods was not statistically significant, which demonstrates that observational studies can help answer relevant research hypotheses [4]. However, while observational studies yield useful data, they utilize natural conditions and are not designed for clinical trials where medical treatment is introduced. Naturally, experiments are used to design clinical trials in which some form of intervention is studied [2]. The gold standard of an interventional clinical trial is the randomized controlled trial (RCT) [5]. RCTs are often considered the “gold standard” because it is the only proven method that can reduce bias by ensuring that those receiving the study treatment and those receiving placebo are as equal as possible in regard to known and unknown variables [6]. To bolster this claim, Schulz et al. credit randomization, avoidance of exclusions after entering the trial, and blinding as the keys to the RCTs superiority. They go on to state that studies that do not include these three criteria tend to generate questionable data [7]. Sackett et al. further support the idea that RCTs are the gold standard of clinical trials because they frequently provide useful outcomes and are so rarely misleading [8]. However, certain biases have recently questioned the validity of RCTs. As an example, a study of five empirical methodological studies has shown that RCTs that produce positive results, meaning that the item or drug under study in the RCT did produce a statistically significant result, are more likely to be published and published quickly than RCTs that create negative results, meaning the item or drug under study did not produce a statistically significant result. This effect is known as publication bias, and it argues that because RCTs that produce positive results are more likely to be published, the RCT is itself a biased method of reporting data [9, 10]. Regardless of these arguments, however, RCTs are still widely used for designing clinical trials.