Hyaluronic Acid Treatment for Osteoarthritis

This assignment analyzes the effectiveness of hyaluronic acid as a treatment for osteoarthritis. It examines research findings, including statistically significant improvements in BPI (Brief Pain Inventory) and Harris Hip Score scores following treatment. The study's power and effect size contribute to its clinical significance, demonstrating that a single hyaluronic acid injection can be effective even in severe cases. The assignment also emphasizes patient satisfaction and adherence rates.

Running head: STATISTICAL ANALYSIS ON CLINICAL TRIAL
Statistical Analysis on Clinical Trial
Name of the Student:
Name of the University:
Author’s note:

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Executive Summary:
This report is initially designed to measure the influence of non-operative treatment of hip and
knee osteoarthritis using two kinds of infiltrations. A comparison is structured from control-
group infiltration. By establishing the study design, researchers would like to contribute a
specific research on non-operative treatment of osteoarthritis of the knee and hip to prevail bias
for the double-blinded randomized trial. The report is based on data collection, data analysis and
interpretation of the data. The measure at the time of enrolment of the research prior to injection
or baseline is administered and followed-up for three or six months. The recovery of patients
according to the two different doses is analysed and determined.

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Table of Contents
Introduction and Background:.........................................................................................................4
PICO question:.................................................................................................................................4
Study Purpose:-................................................................................................................................5
Rationale of the Research:-..............................................................................................................5
Description of how it meets the inclusion criteria:-.........................................................................5
Research Question of the study:-.....................................................................................................6
Does the study’s research question (PICO) match your question PICO?.......................................6
Research Design:-............................................................................................................................6
Research Inclusion Criteria:........................................................................................................6
Research Exclusion Criteria:.......................................................................................................7
Randomized assignment of patients to treatments.......................................................................7
Detection of similarity of groups at the start of the trial..............................................................8
Whether group were treated equally aside from the allocated treatment....................................8
Sampling Methods:-.........................................................................................................................8
Blinding:-.....................................................................................................................................8
Description of Samples:-.................................................................................................................9
Research Methodology:-................................................................................................................10
Subject Mortality:-.........................................................................................................................10

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Study Results:-...............................................................................................................................10
Treatment Effect:-..........................................................................................................................10
Power or Effect Size of the study adequate:-.................................................................................11
Statistical methods used for data analysis:-...................................................................................11
Study results:-................................................................................................................................12
Study limitations:-.........................................................................................................................12
Significance of the clinical result:-................................................................................................12
References:-...................................................................................................................................13

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Introduction and Background:
Osteoarthritis is a general form of arthritis. In pathology, it is characterised by both focal
loss of articular cartilage and marginal, central bone function. Knee and backbone are the major
regions where arthritis symptom most frequently observed. The attributed risk of disability to
knee arthritis may cause due to cardiac diseases and due to any medical disorders permanently.
Intra-articular hyaluronic acid is well established as a treatment of osteoarthritis of knee
and hip. However, the osteoarthritis is not based on randomised controlled trials.
PICO question:
Does intra-articular injection of Hyaluronic acid provide more clinical efficacy than
standard corticosteroid injection in managing patients with major joint osteoarthritis?
P: Patients with osteoarthritis in major joints like hip, knee or shoulder.
I: Intra-articular injection of Hyaluronoc acid.
C: Standard corticosteroid injection
O: Clinical efficacy as well as Outcome.
Journal article:
Colen, S., van den Bekerom, M. P., Bellemans, J., & Mulier, M. (2010). Comparison of intra-
articular injections of Hyaluronic Acid and Corticosteroid in the treatment of
Osteoarthritis of the hip in comparison with intra-articular injections of Bupivacaine.
Design of a prospective, randomized, controlled study with blinding of the patients and

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outcome assessors. BMC Musculoskeletal Disorders, 11, 264.
http://doi.org/10.1186/1471-2474-11-264
Study Purpose:-
The aetiology of Osteoarthritis is multifactorial and involves both generalised factors
such as aging, sex, obesity, heredity and adverse mechanical factors such as trauma, recreational
usage and alignment. We observe a significant genetic component to the prevalence of
osteoarthritis with the heritability estimates of known environmental or demographic
confounder. Standard corticosteroid injection is the conventional method to enhance quality of
life and increase functional capacity in osteoarthritis. It is to observe whether intra-articular
injection of Hyaluronic acid is sufficient for the disease or standard corticosteroid injection could
perform better with efficiency (Zhang et al., 2007). Blinding of the patients and outcome
assessors handled design of prospective randomized and the controlled study.
Rationale of the Research:-
This article should be included for future analysis in Capstone project, since it describes
the effect of a single dosage of hyaluronic acid for treatment of hip osteoarthritis. The results
appear to be stable after 3 months of administration and continuous improvement is observed for
up to 1 year.
Description of how it meets the inclusion criteria:-
The current study satisfied all inclusion criteria. Participants consisted of both sexes that
are males and females with severe osteoarthritis who underwent Standard corticosteroid injection

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in an impatient setting along with outpatient follow-up. The study was performed among 315
intervention trials. Two treatment modalities were identified in which conventional and modern
treatments are undertaken. According to the outputs of the literature search and expert opinion,
10 recommendations for the treatment of osteoarthritis were executed using a five-stage Delphi
technique. Participant characteristics match inclusion criteria of medical diagnoses and disease
severity.
Research Question of the study:-
The research design is a randomized control trial comparing the effectiveness and safety
of treatment methods.
The major question is to determine the safety and efficacy of intra-articular injection of a
high molecular weight hyaluronic acid (Coxarthrum) to treat hip osteoarthritis.
Does the study’s research question (PICO) match your question PICO?
The research does not appropriately compare the efficacy of intra-articular injections of
corticosteroid and hyaluronic acid. It is also not matching with the result of Coxathrum
implementation and showed effect.
Research Design:-
Research Inclusion Criteria:
 Patients, males and females, ages 18 years and above, who have been diagnosed with hip,
knee, or shoulder osteoarthritis.
 Inpatient and outpatient.

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 Randomized controlled trials or Meta-analysis or systemic review.
 A study sample size of at least 30 patients.
 Peer-reviewed English references published from 2000 to 2017.
 Types of interventions:
 Intra-articular HA Injection
 Intra-articular CS Injection
Research Exclusion Criteria:
 Patients with OA who are less than 18 years old.
 Patients with OA who are not candidate for intra-articular HA or CS injection
 Patients with OA who have psychiatric issues, language or intellectual problems, or
suspected potential noncompliance with protocol.
 Pregnant or breastfeeding patients.
 Patients with OA who have allergy or hypersensitivity to any of the study medications or
to contrast solutions.
Randomized assignment of patients to treatments
Centralized computer randomization is ideal. The methods section indicates that the
patients were allocated to groups based on the presence of partial hip disease, hampered by hip
disease for three months and those with good joint mobility. However, the researchers carried out
an unblended study that is not favourable for randomized clinical trials.

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Detection of similarity of groups at the start of the trial
A table is not provided that compares the variable outcomes associated with age of
patients and risk factors. Patients meeting all eligibility criteria and consenting to participate
were randomly assigned to Standard corticosteroid injection group wise.
Whether group were treated equally aside from the allocated treatment
Yes, there are groups treated equally apart from the allocated treatment. It is a three-
armed and parallel-group design. Approximately 315 patients complying with the inclusion and
exclusion criterion would be randomized into the following treatment group: infiltration of the
hip joint with hyaluronic acid with a intra-articular injection.
Sampling Methods:-
Beneficial sampling was used for participant recruitment due to the specificity of the
research question. With the random assignment, initial random selection of subjects was
performed. We gathered time series data not the cross-sectional data due to long follow up.
Patients within treatment facilities were extensively evaluated for inclusion and clinical trial
eligibility was further confirmed by a national screening committee (Özgüçlü et al., 2010).
Stratified randomization was used with the help of blinding technique in forming the two
intervention groups with regard to proportional representation of study centre and access site.
Blinding:-
Blinding is a method by which one or more than one parties in a trial are remained
unaware of which patients of the treatment have been implicated to. Blinding is a crucial aspect

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of any trial done for avoiding and preventing conscious or unconscious bias in the design and
executed of a clinical trial.
Blinding is a randomized, masked-observer, controlled trial that has three-armed parallel-
group design. Patients fulfilling the inclusion or exclusion criteria would be randomized to one
of the following treatment groups:
1. Hyaluronic Acid infiltrates of hip joint
2. Corticosteroids infiltration of hip joint
A block randomization scheme with a block size equal to eight would be used for the
randomization. The researcher takes into account for ignoring random imbalances in group-size
(Chang et al., 2013). The randomization does not consider stratification variables. After the
injection, efficacy parameters would be assessed at baseline and the structured follow-up visits at
six weeks, three months and six months.
Description of Samples:-
Among the treated 351 patients, 80% power to identify in both the groups in comparison
to placebo and clinically meaningful difference in change of VAS and HSS. The standard
deviation of VAS and HSS are assumed to be 20 and 16 respectively. Totally, 285 patients are
required, assuming a moderate correlation of 0.5 between the measurement at baseline and after
6 months. The number of involved subjects would be enhanced by 10% for compensating the
loss of power because of patients with missing observation.

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Research Methodology:-
The study was executed across 45 clinical centres across the country and involved the
suffering patients suffering from osteoarthritis. Prescribed both types of doses were used with
each patient and consistent protocol for medication management was implemented. The
following outcome measuring instruments would be evaluated at baseline before the intra-
articular injection of the study (Lin et al., 2004). Prior to discharge, participants underwent the
follow-up assessments that were also performed at 3 and 6 months post-intervention.
Subject Mortality:-
The subject mortality is between 5%-10%. This percentage of patients entered the clinical
trial but could not attribute the conclusion.
Study Results:-
1. BPI changes were highly significant in case of the worst pain category after 6 months
of treatment.
2. BPI changes were highly significant in case of the mean pain category after 6 months
of treatment.
3. No adverse cases were noted.
4. 12 cases were associated with pain as a result of transient “synovitis”.
Treatment Effect:-
A sterile, transparent, homogenous and visco-elastic preparation consisting of a pure
form of hyaluronic acid was used. It did not contain any avian protein and was not cross linked

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to a chemical agent, which reduces the risk of allergy and other cytotoxic reactions (Bellamy et
al., 1988). Injections were given following fluoroscopic guidance. We observed the Relative
Risk Reduction (RRR) that shows us the decrement in the result rate in the treatment group
relative to the control group.
Relative Risk <1: Treatment decreases the risk of outcome
Relative Risk >1: Treatment enhanced the risk of the outcome
Relative Risk =1: No effect.
Power or Effect Size of the study adequate:-
Patients were divided into those who have partial hip disease, prevailing hip disease for at
least 3 months and those with good mobility of joints. 315 patients were taken and BPI, Harris
Hip Score were determined. A single high molecular weight hyaluronic acid dosage was found to
be safe. It was found to be effective to control pain in patients suffering from hip arthritis. In next
article, the results of clinical trial of the BPI interference score measured in three and six months
post-intervention, is found to be significant.
Statistical methods used for data analysis:-
Categorical variables (e.g., age, gender) were evaluated by Fisher’s exact test or chi-
square, and continuous variables (e.g., burden of illness, quality of life and pain of arthritis) were
measured through means and standard deviations, and t-tests. Analysis was performed using the
SAS software package.

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Study results:-
This randomized and controlled study perhaps would provide robust information on intra-
articular treatments applied in osteoarthritis compared to traditional doses. In second case, the
trend of T0+3 months trial indicate that the result is stable to be continued based on single IA of
HA implementation.
Study limitations:-
Testing sites were not randomly selected, but any bias appeared to be well controlled
though strict patient eligibility criteria, a national oversight panel, and uniform procedures.
Closely observed protocols may have mitigated any potential concern there. The study’s power
and effect size were noted, which provide greater meaning to clinical significance as well as
meeting the threshold for statistical significance (Arroll and Goodyear-Smith, 2004).
Significance of the clinical result:-
Statistically significant scores were obtained in case of BPI and Harris Hip Score
following treatment. The results were also clinically significant as a single hyaluronic acid
dosage was found to be effective for treatment in the aspect of the worst case scenario ( Leblan,
Chantre and Fournie, 2000). Rates of patient at follow-up were comparable between groups,
which contributes to this group’s PICO question.

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References:-
Arroll, B., & Goodyear-Smith, F. (2004). Corticosteroid injections for osteoarthritis of the knee:
meta-analysis. Bmj, 328(7444), 869.
Bellamy, N., Buchanan, W. W., Goldsmith, C. H., Campbell, J., & Stitt, L. W. (1988).
Validation study of WOMAC: a health status instrument for measuring clinically
important patient relevant outcomes to antirheumatic drug therapy in patients with
osteoarthritis of the hip or knee. The Journal of rheumatology, 15(12), 1833-1840.
Chang, K. V., Hsiao, M. Y., Chen, W. S., Wang, T. G., & Chien, K. L. (2013). Effectiveness of
intra-articular hyaluronic acid for ankle osteoarthritis treatment: a systematic review and
meta-analysis. Archives of physical medicine and rehabilitation, 94(5), 951-960.
Leblan, D., Chantre, P., & Fournie, B. (2000). Harpagophytum procumbens in the treatment of
knee and hip osteoarthritis. Four-month results of a prospective, multicenter, double-
blind trial versus diacerhein. Joint, bone, spine: revue du rhumatisme, 67(5), 462-467.
Lin, J., Zhang, W., Jones, A., & Doherty, M. (2004). Efficacy of topical non-steroidal anti-
inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised
controlled trials. Bmj, 329(7461), 324.
Özgüçlü, E., Çetin, A., Çetin, M., & Calp, E. (2010). Additional effect of pulsed electromagnetic
field therapy on knee osteoarthritis treatment: a randomized, placebo-controlled study.
Clinical rheumatology, 29(8), 927-931.
Pham, T., van der Heijde, D. M. F. M., Altman, R. D., Anderson, J. J., Bellamy, N., Hochberg,
M., ... & Dougados, M. (2004). OMERACT-OARSI initiative: Osteoarthritis Research
Society International set of responder criteria for osteoarthritis clinical trials revisited.
Osteoarthritis and Cartilage, 12(5), 389-399.

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Zhang, W., Moskowitz, R. W., Nuki, G., Abramson, S., Altman, R. D., Arden, N., ... &
Dougados, M. (2007). OARSI recommendations for the management of hip and knee
osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic
review of current research evidence. Osteoarthritis and cartilage, 15(9), 981-1000.