The Purpose and Population for the Investigation
Study hypothesis
The research aims at evaluating the efficacy of purified honey bee (Apis mellifera) venom (HBV) biotherapy for the treatment of osteoarthritis (OA) knee pain and physical function.
Study population
The study population under research comprises of patients with osteoarthritis (OA). The inclusion criteria for the subjects of investigation consist of the prevalence of at least one knee, which has been determined to be Kallgren-Lawrence radiograph grade of between one to three. For inclusion, the patient is also necessitated to possess moderate to severe knee pain. This pain is categorized by a score of greater or equal to two on question Number one of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Moreover, the subjects were required to be under chronic pain medication for not less than four days/week in 28 days before screening. The exclusion criteria for topics for the study include hypersensitivity to bee venom or the prevalence of a positive skin test to honey bee venom (HBV).
Patients with IS injection of hyaluronic acid, corticosteroids, or IA viscosupplementation were excluded from the study. Patients with the general usage of chronic oral antihistamines, Beta-blockers, simultaneous injury, or inflammation of the target knee were excluded from the study. Furthermore, subjects under inhibitors of cytochrome P450 enzyme isoforms were also excluded from the study.
Sample Size and Statistical Power
932 patients were screened; however, only 538 patients were enrolled for the study. A total of 361 patients were randomized for the Honey Bee Venom, while 177 subjects were selected as a control group for the study. Statistical power refers to the likelihood that a certain test will correctly reject a false null hypothesis. Therefore, the higher the statistical power for a given experiment, the lower the probability of committing a type two error. The statistical power for the study is 90% which means when a series of trials is run on the drug and placebo; the chances are 90% to get a statistically significant result (Conrad et al., 2019). The power also means there is a 10% probability for the results not to be statistically significant.
Selection of Participants for the Study and Control Groups
Process
The study utilized a randomized approach to identify and assign subjects to experimental or control groups.
Confounding variables
The confounding variables refer to a set of variables that affect other variables within a study to produce distortion between the variables. The confounding variables tend to influence both the independent and the dependent variables, leading to a spurious association. The confounding variables within the study include the prevalence of exercise and weight loss. The variables also entail use of prohibited medications, systemic reaction to the HBV hypersensitivity skin test, or recent use of an investigational product.
Masking or blinding
Masking or blinding was evident in the research as the double-blind study was used for the clinical trials.
Measurement of outcomes or endpoints in the study and control groups
Appropriate
The study undertook different assessments to determine whether purified honey bee (Apis mellifera) venom (HBV) biotherapy can offer alternative treatment of osteoarthritis (OA) knee pain and physical function. Some of the assessments employed by the study include global physician assessment (PGA) and physical functioning subscales to assess the physical functioning of the subjects after being treated to the medication or the placebo. Other assessments used to determine subjects’ pain include the WOMAC pain and the global patient assessment (PGA). To ensure that the outcomes or endpoints of both the control and study groups are adequately assessed, rescue medication usage was also evaluated. The routine safety parameters were also closely monitored to determine the study’s outcome.
Comparison of outcomes in the study and control groups
Estimation
The HBV biotherapy showed an increasingly significant improvement compared to the control within the WOMAC pain score after 12 weeks that was also upheld in the four weeks post-treatment. In addition, the WOMAC physical function was high among the control compared to the HBV for 12 weeks and four weeks post-treatment. The VAS scores were relatively high within the HBV subjects compared to the control group and PGA and PGA assessments. An estimated 77%-78% of the subjects from the two groups used rescue acetaminophen (Conrad et al., 2019). Additionally, HBV was highly associated with cases of injection site reaction. Nonetheless, the safety profiles between the two groups were comparable.
Inference/Adjustment
The analysis of variance (ANOVA) technique is one of the statistical methods used in the study to investigate whether the differences between the HBV and controlled groups bear any statistical significance. Another method used in the research includes ANCOVA, which entails a blend of ANOVA and regression. The study also employs the one-sample median test, which investigates whether or not a significant difference exists between the hypothesized media and the real median of a sample.
Statistical technique(s) used to take into account or control for potential
Confounding variables
Some of the available statistical techniques essential in taking into account or controlling the likelihood of confounding variables include the logistic regression technique that yields results that can be interpreted as an odds ratio. Other methods include multivariable regression analysis, restriction, and matching, which are essential to control confounding variables during the analysis phase. The research utilized the randomization technique to control confounding variables that should not or cannot be held constant.
Meaning of the results for those included in the investigation
Contributory Cause or Efficacy
According to the phase 3 trial findings, the usage of HBV on the subjects was found to enhance improvement in the physical function and OA pain significantly and alleviate undesirable outcomes.
Harms and interactions
The study identifies different adverse effects and interactions that can influence the meaning of the results. Some of the adverse events (SAEs) placed on patients subject to the study include pneumonia aspiration, anaphylactic reaction, sinus Bradycardia, diverticulitis, and sinus bradycardia. The anaphylactic reaction was common among Subjects who regularly received an injection at shorter intervals than recommended by the protocols.
Subgroups
There is a similarity in the outcomes observed within subgroups under investigation and the overall results for the study. For instance, regarding safety, the percentage of subjects reporting at least one treatment-emergent AEs (TEAEs) for HBV and control groups was 49.0% and 46.3%, respectively (Conrad et al., 2019). These outcomes are similarly observed in the overall investigation sites that the overall safety profile was comparable to control-treated patients. Likewise, effects observed by Conrad et al. (2019) the baseline reveal that the HBV sub-group responded to the treatment positively as “very good” and “good” compared to the control sub-group (20.9%, 61.1% and 23.3%, 39.1%, respectively). These outcomes conform to the overall effects of the study where VAS pain assessments ascertained the efficacy of HBV treatment over control. The efficacy results of HBV have further been categorized as comparable to those of the Synvisc-One (hyaluronan viscosupplement). The Synvisc-One is an intra-articular injection used to treat pain in the osteoarthritic knee.
Meaning for those not included in the investigation
To similar individuals, groups or populations
The researchers finally extrapolate the conclusions of the study to groups and individuals. They recommend the usage of HBV injections as a potential treatment alternative to patients who fail to respond to nonpharmacologic therapy and traditional analgesics like acetaminophen positively.
Beyond the data
The investigators revealed that HBV had been found effective in improving knee OA pain and physical function for a period extending to four weeks post-treatment.
To other populations
The investigators revealed that the HBV and Control groups patients were African Americans and Whites. This data shows that the study’s findings can only be generalized to these races. In addition, Conrad et al. (2019) reveals that the populations of African Americans in the control group were higher than those within the HBV group (32.3% and 24.4%, respectively).
Brief Summary of the Article
Clinical decisions entail analyzing different information, assessing the available evidence, and administering significant knowledge to pick interventions that ensure quality care and minimum risk to the patient. As patients respond differently to certain treatment plans, it becomes essential for clinicians to review available evidence. The review helps develop evidence-based practices that explore alternative interventions to certain conditions. Different patients have shown poor responses to simple analgesics and nonpharmacologic therapy interventions to knee OA pain and physical functioning. The research provides evidence by analyzing the results of clinical trials carried on a control group and an HBV group. The study recommends the usage of HBV intervention to address knee OA pain and physical functioning. However, it is essential to note that clinical trials have only been done on whites and African Americans. Nonetheless, the available evidence reveals that the majority of patients who have been subjected to the treatment have defined it as “very good” and “good.”
The study has a commendable statistical power of 90%; high statistical power is significant to develop accurate conclusions regarding a certain effect if development is found. In addition, the study sample size and response rate are relatively good. However, the research lacks more depth as there is insufficient representation of different races or a review of various studies done on the same topic across different cultures. This information would improve the generalization of the study results across diverse populations. This study has been crucial to improving personal understanding of available evidence of alternative treatment interventions for osteoarthritis (OA) knee pain and physical function.
Work Cited
Conrad V, Hazan L, Latorre A, Jakubowska A, Kim C. Efficacy and Safety of Honey Bee Venom (Apis mellifera) Dermal Injections to Treat Osteoarthritis Knee Pain and Physical Disability: A Randomized Controlled Trial. The Journal of Alternative and Complementary Medicine. 2019;25(8):845-855.