CRITICALLY APPRAISED TOPIC

TITLE

Notes on the Title

The title may or may not be declarative (ie one that declares the findings of the appraisal). If a series of studies are
being appraised and synthesised into a CAT, it may be better to use a more descriptive title (eg Effectiveness of X or Y
for children with autism)

For previous examples, see CAPs in Australian Occupational Therapy Journal and previous CATs on the OT CATS
website.

It is suggested that authors do NOT include the level (eg 1b) in the title since the difference countries/organisations use
different hierarchies, and the terms can have different meanings for studies of therapy effectiveness vs
prognostic/diagnostic studies

AUTHOR
Prepared by

Date

Email address
Review date

(date discussed in class)

Facilitators Name

CLINIAL SCENARIO

FOCUSSED CLINICAL QUESTION

SUMMARY OF SEARCH
[Best evidence appraised and key findings]

CLINICAL BOTTOM LINE

Important note on the limitation of this CAT

This critically appraised paper (or topic) has /has not been peer-reviewed by one other independent
person/lecturer
Please AIM to FIT AS MUCH OF THE ABOVE INFORMATION ONTO THE FIRST PAGE OF YOUR CAT/CAP

SEARCH STRATEGY
Terms used to guide the search strategy

Patient/Client Group:

Intervention (or Assessment):

Comparison:

Outcome(s):

Databases and Sites Searched

Pubmed -Medline

INCLUSION and EXCLUSION CRITERIA

Inclusion Criteria

Exclusion Criteria

Search Terms

Limits Used

RESULTS OF SEARCH ( No need to answer )

A total of

___

(insert number) relevant studies were located and categorised as shown in Table 1 (based on
Levels of Evidence, Centre for Evidence Based Medicine, 2011)

Table 1: Summary of Study Designs of Articles Retrieved

Study Design/Methodology of Articles Retrieved

Level

Number Located

Author (Year)

Note
If you search for and locate evidence-based clinical guidelines, note this at the end of your table,
and include in your reference list. The level of evidence should be recorded as Not Applicable (NA)
for qualitative studies, and a footnote added to identify levels for non- intervention studies (i.e.
prognostic or diagnostic).

BEST EVIDENCE
The following study/paper was identified as the best evidence and selected for critical appraisal. Reasons for
selecting this study were:

The study met the inclusion and exclusion criteria.

The study is valid and relevant.

SUMMARY OF BEST EVIDENCE ( JOURNAL GIVEN TO YOU AS EXERCISE )

Table 2: Description and appraisal of (name study design) by (authors, Year)
Aim/Objective of the Study/Systematic Review:
The study aims to assess the safety and immunogenicity of a quadrivalent human papillomavirus (qHPV)
vaccine in sub-Saharan African women.
The primary immunogenicity hypothesis was that an acceptable percentage of subjects who received the qHPV
vaccine seroconvert to HPV6/11/16/18 at 4 weeks post-dose 3, defined as the lower bound of the corresponding
95% confidence interval (CI) exceeding 90%.
The primary safety objective was to demonstrate that qHPV vaccine was generally well tolerated when
administered in a 3-dose regimen.
Study Design
[eg systematic review, cohort, randomised controlled trial, qualitative study, grounded theory. Includes
information about study characteristics such as blinding and allocation concealment. When were outcomes
measured, if relevant]
Note:
For systematic review, use headings search strategy, selection criteria, methods etc.
For qualitative studies, identify data collection/analyses methods

The seven-month, double-blind study enrolled 250 healthy, human immunodeficiency virus (HIV)-uninfected
females ages 926 residing in Ghana, Kenya, and Senegal. Thirty females ages 1315 and 120 females ages
1626 received qHPV vaccine. In addition, 100 females ages 912 y were randomized in a 4:1 ratio to receive
either qHPV vaccine (n D 80) or placebo (n D 20 ).

Setting
[eg locations such as hospital, community; rural; metropolitan; country]
The study included participants residing in Ghana, Kenya, and Senegal.
Participants
[N, diagnosis, eligibility criteria, how recruited, type of sample (eg purposive, random), key demographics such
as mean age, gender, duration of illness/disease, and if groups in an RCT were comparable at baseline on key
demographic variables; number of dropouts if relevant, number available for follow-up]
The study enrolled 250 healthy females between the ages of 9 and 26 y (Table 1). Thirty females ages 1315
and 120 females ages 1626 received qHPV vaccine. In addition, 100 females between the ages of 912 y were
randomized in a 4:1 ratio to receive either qHPV vaccine (n D 80) or placebo (n D 20).
The number of participants who entered the study was 250. However, only 206 (82.4%) completed the study.
Among those who discontinued, 8 lost to follow-up, 18 had protocol violation, 1 withdrew from the study, and
17 had unknown cause.
Intervention Investigated
[Provide details of methods, who provided treatment, when and where, how many hours of treatment provided]
Control
The controls received an indistinguishable aluminum-containing placebo. They received the placebo at day 1,
month 2, and month 6 after having a negative result on a pregnancy test (post-pubertal females only) of the
urine.
Experimental
The experimental group received qHPV vaccine with amorphous aluminum hydroxyphos- phate sulfate adjuvant
and visually. They received qHPV vaccine at day 1, month 2, and month 6 after having a negative result on a
pregnancy test (post-pubertal females only) of the urine.
Outcome Measures (Primary and Secondary)
Give details of each measure, maximum score for each measure and range, administered by whom, where
For immunogenicity, the seroconversion rates to each of HPV6, 11, 16, and 18 were measured at 95%
confidence intervals (CI). Each seroconversion rate was declared acceptable if the lower bound of the
corresponding 95% CI exceeded 90%. For geometric mean titers (GMT) to each of HPV6, 11, 16, and 18, 95%
CIs were provided with no hypothesis testing. Similar to previous studies, the analyses of immunogenicity was
based on the per-protocol population, which consisted of subjects who had received all 3 vaccinations within
acceptable day ranges, were free of protocol violations, were negative to the relevant HPV type at enrollment,
and had provided a blood sample for month 7 serology testing within an acceptable day range.
The primary safety objective was to demonstrate that qHPV vaccine was generally well tolerated when
administered in a 3- dose regimen. Each subject received a Vaccination Report Card (VRC) on which to record
oral temperatures approximately 4 hours following each vaccination and daily for the next 4 days; any systemic
or injection-site adverse event (AE) that occurred on the day of vaccination or within 14 calendar days following
vaccination; and any concomitant medications or concomitant vaccinations received on the day of vaccination or
during the 14 calendar days following vaccination. The analysis of safety was carried out according to a tiered
approach. VRC-prompted injec- tion-site AEs of pain, swelling and redness, temperature elevations (oral
temperature >37.8C [>100.0F]) and serious AEs were considered Tier 1 events. In addition, the percentage of
patients with any AE, any injection-site AE, any systemic AE, any vaccine-related AE, any serious AE, any
serious vaccine-related AE, and who discontinued due to an AE were considered Tier 2 endpoints. p-Values (Tier
1 only) and 95% CIs (Tier 1 and Tier 2) were calculated for between-treatment differences (qHPV vaccine vs
placebo) following the methods of Miettinen and Nurminen.26 Since randomization between qHPV vaccine and
placebo was confined to the 9 to 12 y age group, all compari- sons within the tiered approach were restricted to
this age group.
Main Findings
[Insert table of mean scores/mean differences/treatment effect, 95% confidence intervals and p-values etc
where provided if you need to calculate these data yourself put calculations here and add interpretation later,
under critical appraisal on next page]

This study demonstrated that qHPV vaccination of sub- Saharan African women was highly immunogenic and
generally well tolerated. The pre-specified statistical criterion for the pri- mary immunogenicity hypothesis was
met: the lower bound of the 95% exact binomial CI on the seroconversion rate exceeded 90% for each vaccine
HPV type and all subjects seroconverted by 4 weeks post-dose 3. Across vaccination groups, the most common adverse events (AE) were at the injection site, including pain, swelling, and erythema.

Since this is a cohort study, the magnitude of the association can be determined by computing for the relative
risk.

Original Authors Conclusions

[paraphrase as required. If providing a direct quote, add page number]
Although HPV vaccination is not a replacement for cervical cancer screening, data from the present clinical
trial, along with existing extensive post-licensure data, suggest that high vaccine uptake in African countries
would result in similar marked decreases in HPV infection and disease as seen in high income nations. (p.
1328)
Critical Appraisal
Validity
[Methodology, rigour, selection, bias, provide PEDro socre/PEDro partitioned score and sub-test items 1-10 for
RCTs; other study designs, follow headings used in critical appraisal checklist forms.
Comment on missing information in original paper.
Methodology

Level of evidence: 1 (RCT)

Double blinded study

Sufficiently long follow-up

Selection/Bias

The study had a well-defined inclusion and exclusion criteria

No statistical differences between characteristics of experimental and control group

Pedro Score

10/11

No clear specification whether there was concealed allocation

Missing information

A significant number of participants were noted to have unknown causes of dropping out from the
study

Interpretation of Results
[Favourable or unfavourable, specific outcomes of interest, size of treatment effect, statistical and clinical
significance, minimal clinically important difference some of which you may have calculated yourself.
Email original authors for information needed such as additional data needed to calculate confidence intervals.
The study is the first study to evaluate the qHPV vaccine in Africa. Though vaccine efficacy was not an endpoint,
a prior sub-analysis of the black women who were enrolled in the large phase 3 efficacy trials of the qHPV
vaccine showed vaccine efficacy against disease caused by HPV6, 11, 16, and 18 was 100% for cervical, vulvar,
and vaginal intraepithelial neoplasia, and condylomata accuminata, among women who were negative to the
vaccine types at study entry. The observed safety findings are also similar to that of other studies, whereby
vaccine recipients have higher rates of injection site pain, erythema and swelling, but similar rates of systemic
AEs.
The relative risk was computed as 1.07, which means that the adverse effects may be causing harm but is not

significant.
Summary/Conclusion
The study has properly demonstrated the immunogenicity of qHPV vaccine and its possible adverse effects
among sub-Saharan African women. The study had a clearly defined inclusion and exclusion criteria, and the
procedure to which they validates the criteria were thoroughly explained. There were no statistical differences
between characteristics of experimental and control group. However, a significant number of participants were
noted to have unknown causes of dropping out from the study, and this may yet have to be accounted for.
There was also no clear specification whether there was concealed allocation.
Repeat the above table as needed for additional studies included in the CAT.
If more than one paper is included, an additional table that provides a comparative summary of
each paper may be added.
(Do not answer this part)
Table [x]: Characteristics of included studies
Study 1

Study 2

Study 3

[Author and Year]

[Author and Year]

[Author and Year]

Intervention investigated
Comparison intervention
Outcomes used
Findings

(PLEASE ANSWER THIS)

IMPLICATIONS FOR PRACTICE, EDUCATION and FUTURE RESEARCH
The study demonstrated the qHPV effect on sub-Saharan African women. This is relevant especially
because the government sometimes implements mass immunization for prevalent diseases, and this
kind of study may be of help in assessing the cost-effectiveness of such programs. This will also
help clinicians in their country in anticipating the possible adverse effects of vaccination using
qHPV. The study is also reproducible in different countries if ever researchers wish to evaluate the
immunogenicity and safety of qHPV in different race or nationalities.
Notes

This section synthesises your comments from appraisal section, and may mention other related research,
both quantitative and qualitative.
Comment on whether the intervention is used in practice in your region/country, cost of that treatment,
need for education of local therapists/undergraduates about this intervention and/or outcome measures
used in the study).
Students may wish/need to discuss implications with clinicians for suggestions
Read recent CATs from the OT-CATS website and CAPS in Australian Occupational Therapy Journal for ideas
to include in this section.

REFERENCES
[List references in alphabetical order using APA style and format]
Evaluation of safety and immunogenicity of a quadrivalent human papillomavirus vaccine in healthy females
between 9 and 26 years of age in Sub-Saharan Africa by Mugo et al. Human Vaccines & Immunotherapeutics
11:6, 1323-1330; June 2015; Merck and Co., Inc.

AIM TO SUMMARISE YOUR CAT IN 8-12 PAGES iF ONLY APPRAISING ONE KEY STUDY (CAP=
Critically Appraised Paper).

A LONGER DOCUMENT IS ACCEPTABLE IF YOU ARE APPRAISING AND SYNTHESISING SEVERAL

STUDIES (CAT = Critically Appraised Topic).