Introduction Clinical trial design impacts Level of Evidence Clinical trials may be either observational or experimental observational researchers observe patient groups without allocation of intervention may be either prospective or retrospective may be descriptive or analytic descriptive useful for obtaining background information for more advance studies examples case reports case series cross-sectional studies analytic explores the association between a given outcome and a potentially related variable examples case-control cohort meta-analysis experimental researchers allocate treatment allows the evaluation of efficacies of therapeutic interventions examples double-blinded, prospective, randomized clinical trial is the gold standard for evidence based medicine Randomized controlled trial Definition a study in which patients are randomly assigned to the treatment or control group and are followed prospectively provides the most compelling evidence that the study treatment causes the expected effect on human health randomization minimizes study bias Study designs Parallel-group each participant is randomly assigned to a group, and all the participants in the group receive (or do not receive) an intervention, Crossover administration of two or more therapies, one after the other, in a random order susceptible to bias if washout period is inadequate Factorial each participant is randomly assigned to a group that receives a particular combination of interventions or non-interventions. Cluster pre-existing groups of participants (e.g., villages, schools) are randomly selected to receive (or not receive) an intervention. single blinded study vs. double blinded study Analysis intent-to-treat analysis outcomes based on the group into which they were randomized, regardless of whether the patient actually received the planned intervention minimizes non-responder bias per protocol excludes patients who were not compliant with the protocol guidelines Example you want to determine whether your new toothpaste prevents cavities better than your old toothpaste. You randomly assign a large number of patients to either an intervention group, which uses the new toothpaste, or to a control group, which uses the old toothpaste. You would then measure the amount of cavities between the groups over time. Orthopaedic Literature Examples Surgical vs nonoperative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT): a randomized trial. JAMA. 2006. Should insertion of intramedullary nails for tibial fractures be with or without reaming? A prospective, randomized study with 3.8 years' follow-up. J Orthop Trauma. 2004. Nonoperative treatment compared with plate fixation of displaced midshaft clavicular fractures. A multicenter, randomized clinical trial. J Bone Joint Surg Am. 2007. Cohort study Definition a study in which patient groups are separated non-randomly by exposure or treatment, with exposure occurring after (prospective), or before (retrospective), the initiation of the study Evidence Level II or III evidence Analysis results usually reported as relative-risk Example you want to determine if smoking is a risk factor for the development of lung cancer. You identify a group of smokers and a group of non-smokers, and follow them over time measuring the desired outcome, in this case, lung cancer. Orthopaedic Literature Examples A prospective cohort study of the effects of lower extremity orthopaedic surgery on outcome measures in ambulatory children with cerebral palsy. J Pediatr Orthop. 2009. Functional outcomes following displaced talar neck fractures. J Orthop Trauma. 2004. Risk of revision for fixed versus mobile-bearing primary total knee replacements. J Bone Joint Surg Am. 2012. Case-control study Definition a study in which patient groups are separated by the current presence (cases) or absence (controls) of disease and examined for the prior exposure of interest Evidence Most are Level III evidence Analysis usually reported as odds-ratio Example you want to determine if smoking is a risk factor for the development of lung cancer. You compare the smoking history of individuals with lung cancer (cases) and those without (controls). Orthopaedic Literature Examples Fluoride in drinking water and risk of hip fracture in the UK: a case-control study. Lancet. 2000. Risk factors for retained instruments and sponges after surgery. N Engl J Med. 2003. Risk factors and short-term mortality of venous thromboembolism diagnosed in the primary care setting in the United Kingdom. Arch Intern Med. 2007. Meta-analysis Definition a systematic review that summarizes results of other studies Evidence may be used in increase the statistical power of several under-powered studies Example you want to determine if wearing sunscreen results in fewer cases of melanoma. You pool the results of 9 randomized controlled studies and statistically analyze the data to determine the effect of the relationship. Orthopaedic Literature Examples Internal fixation compared with arthroplasty for displaced fractures of the femoral neck. A meta-analysis. J Bone Joint Surg Am. 2003. Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies. Spine (Phila Pa 1976). 2006. Influence of osteoporosis on fracture fixation--a systematic literature review. Osteoporos Int. 2008. Cross-sectional Study Definition study group is analyzed at a given time ("snapshot") with no follow-up Example you want to determine the prevalence of baseball injuries during the 2003 little-league season Orthopaedic Literature Examples Variability in the definition and perceived causes of delayed unions and nonunions: a cross-sectional, multinational survey of orthopaedic surgeons. J Bone Joint Surg Am. 2012. Hypovitaminosis D in patients scheduled to undergo orthopaedic surgery: a single-center analysis. J Bone Joint Surg Am. 2010. Treatment preferences for displaced three- and four-part proximal humerus fractures. J Orthop Trauma. 2010. Case Series Definition a retrospective account of multiple patients with the same injury or treatment with no control or comparison group useful for generating hypotheses for additional studies Evidence level IV evidence Example you have found that several of your patients who have used a new lipid lowering medication have developed hemorrhagic cysts. You want to alert other members of the community of this possible association. Orthopaedic Literature Examples Familial bilateral osteochondritis dissecans of the femoral head. J Bone Joint Surg Am. 2009. Familial osteofibrous dysplasia. A case series. J Bone Joint Surg Am. 2005. Treatment of posterior cruciate ligament tibial avulsion fractures through a modified open posterior approach: operative technique and 12- to 48-month outcomes. J Orthop Trauma. 2008.
QUESTIONS 1 of 8 1 2 3 4 5 6 7 8 Previous Next You have 100% on this question. Just skip this one for now. Take This Question Anyway (OBQ13.195) A study was designed to measure the benefit of subacromial corticosteroid injections. Participants were randomized to methylprednisolone acetate 40 mg with lidocaine 1% or lidocaine 1% alone. The participants were not provided with information of their treatment allocation. The subacromial injection was prepared and administered by a single orthopaedic surgeon. Results were collected by the orthopaedic surgeon using clinical and patient satisfaction outcome scores at 6, 12, and 24 weeks. Which of the following would best describe this type of study? Review Topic | Tested Concept QID: 4830 Type & Select Correct Answer 1 Double blinded randomized and controlled study 4% (159/4268) 2 Single blinded randomized study 89% (3780/4268) 3 Retrospective study 1% (28/4268) 4 Case-control study 2% (85/4268) 5 Prospective cohort study 4% (183/4268) L 1 Question Complexity B Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK You have 100% on this question. Just skip this one for now. Take This Question Anyway (OBQ11.243) A clinical trial is underway for patients with wrist extensor tendinitis. One group of 100 patients are treated with short arm casting. Another group of 100 patients are treated with physical therapy. During analysis of the results, it becomes apparent that 30 patients in the physical therapy group did not complete the full course of physical therapy. Despite not completing a full course of physical therapy, these 30 patients were included in the physical therapy group for analysis. This analysis is an example of which of the following? Review Topic | Tested Concept QID: 3666 Type & Select Correct Answer 1 Per-protocol 6% (361/5677) 2 Crossover analysis 6% (327/5677) 3 Intent-to-treat 79% (4505/5677) 4 Bayesian analysis 5% (264/5677) 5 Effect size 3% (170/5677) L 2 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 Sorry, this question is for PEAK Premium Subscribers only Upgrade to PEAK You have 100% on this question. Just skip this one for now. Take This Question Anyway (OBQ09.34) What is the primary purpose of utilizing a computer random number generator for patient randomization when designing a Level I therapeutic controlled trial? Review Topic | Tested Concept QID: 2847 Type & Select Correct Answer 1 To increase treatment effect 0% (2/713) 2 To prevent selection bias 97% (691/713) 3 To generate enough power 1% (4/713) 4 To achieve statistical significance 2% (12/713) 5 To perform as-treated analysis 0% (1/713) L 1 Question Complexity D Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2 You have 100% on this question. Just skip this one for now. Take This Question Anyway (OBQ05.86) A clinical study for lateral epicondylitis allocates 1 group to receive physical therapy for 4 weeks and another group a new oral medication for 4 weeks. Then the 2 groups immediately switch therapies with one another for the next 4 weeks. The half-life of the medication used in the study is 2 weeks. Which of the following best describes the bias that is present in this study design? Review Topic | Tested Concept QID: 972 Type & Select Correct Answer 1 Recall bias 5% (51/1054) 2 Verification bias 4% (37/1054) 3 Washout period bias 74% (783/1054) 4 Detection bias 7% (79/1054) 5 Incorporation bias 10% (101/1054) L 2 Question Complexity A Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 3 You have 100% on this question. Just skip this one for now. Take This Question Anyway (OBQ04.149) A research study is initially designed as a high-quality randomized control trial. The study seeks to demonstrate a different clinical outcome with treatment A compared to treatment B for a specific disease. However, at the completion of the study the investigators are only able to obtain 70% follow-up of patients. What level of evidence should be assigned to this study? Review Topic | Tested Concept QID: 1254 Type & Select Correct Answer 1 1 19% (263/1390) 2 2 70% (972/1390) 3 3 9% (125/1390) 4 4 2% (24/1390) 5 5 0% (3/1390) L 2 Question Complexity C Question Importance Select Answer to see Preferred Response SUBMIT RESPONSE 2
All Videos (0) Podcasts (1) Basic Science | Clinical Trial Design & Levels of Evidence (ft. Dr. Adolph Yates) Team Orthobullets 4 Basic Science - Clinical Trial Design Listen Now 6:57 min 10/18/2019 6 plays