dissertation guidelines

Ali M Ghanem MD PhD

MSc� Aesthetic� Medicine�Dissertation� Guidelines� �

Guidelines for dissertation

The MSc dissertation aims to demonstrate the candidate’s ability to critically appraise a specific area of Aesthetic Medicine, acquisition of in-‐depth knowledge and understanding of the field, ability to provide a rational and systematic discussion of the subject, as well as attainment of academic writing skills.

Candidates should aim to achieve a standard that is suitable for publication in an international peer-‐reviewed aesthetic journal such as Journal of Cosmetic Dermatology, Aesthetic Surgery Journal or the Journal of Plastic Reconstructive & Aesthetic Surgery (JPRAS).

First of all, identify an aesthetic related topic of interest (a list of topics is provided below). You may include clinical findings, images or cases to illustrate your points of discussion. If you are unsure of a topic, you may want to discuss potential areas of interest with the Course Lead.

Once you have your topic and title, you should then perform a thorough up-‐to-‐date extensive literature search* to provide the background to your dissertation. It also ensures that your idea is novel and has the potential to provide new insight for readers of a peer-‐reviewed journal. Once you have read the literature, you can then formulate your own research questions that would inform your practice and perhaps contribute to the field of interest.

The literature search would serve as your introduction and most of your discussion chapter and the methodology and result chapters would be based on three research questions identified through your initial review and answered according to the Best Evidence Topics (BETs) methodology introduced to you through the course (http://www.bestbets.org).

The dissertation is then written accordingly in your own words. You are advised to arrange your dissertation according to the following structure and format. Alternatively, you may follow the structural layout similar to a peer reviewed paper. A list of topics and examples of how to formulate BETs research questions is provided below.

* Appendix 1 provide guidelines for how to perform a systematic literaturereview.

Ali M Ghanem MD PhD

Dissertation Topics

• Scar management – Optimizing the aesthetic outcome• Photoaging – An evidence based treatment approach• Toxins in aesthetic medicine – Innovations and new trends• Toxins in aesthetic medicine – Treatment of a particular indication• Soft tissue augmentation in aesthetic medicine – The upper face• Soft tissue augmentation in aesthetic medicine – The middle face• Soft tissue augmentation in aesthetic medicine – The lower face• Soft tissue augmentation in aesthetic medicine – The periocular area• Soft tissue augmentation in aesthetic medicine – Risk reduction strategies• Soft tissue augmentation in aesthetic medicine – Any other aspect• Peels in aesthetic medicine – Evaluation of efficacy and safety• Peels in aesthetic medicine – Office based choices• Hair loss – Evidence based treatment modalities• Hair transplantation – Evaluation of technical details• Excess hair treatment – A critical evaluation of treatment modalities• Laser treatment for vascularized lesions – An evidence based protocol• Laser skin rejuvenation – An evidence based treatment strategy• Evidence for aesthetic medicine intervention for better quality of life• Psychological consideration in aesthetic medicine – When the practitioner says no• Medicolegal considertations in aesthetic medicine – UK, USA and Australian law• Aesthetic medicine and the law – Optimum regulation strategies (UK law)• Outcome measures in aesthetic medicine• Cosmeceuticals – Evidence based treatment approach• Cosmeceuticals – Critical analysis of current ‘popularized’ strategies• Sclerotherapy – Evaluation of current modalities and alternatives• Optimum skin resurfacing – Microneedling , laser or chemical peels• Mesotherapy – Evaluation of current treatment modalities• Thread lifts – A critical analysis of current treatment modalities• Collagen stimulation agents – A critical analysis of current treatment modalities• Platelet rich plasma in aesthetic medicine – Evidence based treatment approach• Microlipofilling in aesthetic medicine – Evaluation of office based procedures• Non-invasive lipolysis technology in aesthetic medicine – A critical analysis

Ali M Ghanem MD PhD

Example on how to formulate BETs research questions

Dissertation topic:

• Collagen stimulation agents – A critical analysis of current treatment modalities

Introduction and basis for discussion

Conduct an (abstract only) systematic review† of the literature on collagen, collagen synthesis and collagen stimulation products

Identify 7 potential modalities

-‐ Poly L Lactic Acid (PLLA) -‐ Calcium Hydroxylapatite (CaHA) -‐ Polycarpolactone (PCL) and Carboxymethylcellulose (CMC) -‐ Threads (eg polydioxanone (PDO)) -‐ Radiofrequency combined with/without magnetic energy devices -‐ Fractioned laser -‐ Micro-‐needling

Note the first three are injectable whereby the fourth is thread, the fifth/sixth are energy (non-invasive) and laser device and the seventh is mechanical stimulation.

We try to evaluate like with like through a systematic BETs approach through a well-thought and practically orientated 3–part questions (target population / indication – intervention / outcome).

Given the wider range of applications and interventions as well as outcome measures the 3-Part Best Evidence Topic (BET) Questions would present a huge number of possible evaluations and comparisons.

For the purpose of the dissertation, it is necessary to choose an appropriate target population, indications (commonly presenting conditions such as facial aging or hands etc), interventions (popular options such as injectable or technology available devices) and outcome (standardized tools such as PROMs, doctor evaluation, 3-D scanning, biopsy, complications, costs etc).

For example, one might want to evaluate the efficacy and safety of injectable agents vs threads as soft tissue augmentation and collagen stimulation tools in facial rejuvenation.

The thesis would focus on facial rejuvenation (population), and compare all three injectables identified in the literature search above to available threads and discuss this from efficacy, safety and cost effectiveness point of view.

† Appendix 1

Ali M Ghanem MD PhD

1] Efficacy: look up all papers published and evaluate them according to BETscritical appraisal (CA) sheets and compare their important messages (indications, number of subjects, protocol, outcome measure etc) in tables‡.

2] Safety: look up all papers published on complications and evaluate themaccording to severity, frequency, predictive factors (the CA sheets are helpful here too as they will include analysis of follow up duration and if all patients are accounted for etc).

3] Cost analyses (US & UK)§: Try to obtain pricing of products from websites,aesthetic pharmacies and practitioners then use the economic study CA sheet as it would give you the principles of how to conduct a good cost analysis evaluation.

Report these in tables and discuss them according to BETs methodology or other method to report the outcome of systematic reviews in the literature**.

Other students may choose other angles to discuss in the same topic and accordingly other 3-part questions or dissertations on the same topic but different focus might be;

Question Target population/ Indication

Intervention Outcome

1 Facial rejuvenation PLLA/CaHA/PCL vs

PDO threads

Basic science Treatment burden Efficacy (objective* vs subjective#) *3D scan/photo/biopsy#Doctor evaluation #Patient evaluation Durability Complications Cost analysis

2 Hand rejuvenation PLLA/CaHA/PCL vs Radiofrequency/ Laser

Any of above outcomes

3 Décolletage Laser vs micro-‐needling

Any of above outcomes

‡ Use BETs CA sheets (Appendix 2 A & B): include the ones relevant to cohort and case control studies as most of the aesthetic literature would fall under these categories. More sheets are available on http://bestbets.org/links/BET-‐CA-‐worksheets.php) § Use BETs CA sheet (Appendix 2 C)** Appendix 3: 5 steps to systematic review.

Ali M Ghanem MD PhD

Dissertation Structure 1. Title page – This should include the title of your dissertation, your name

and institution, the year of completion 2. Abstract page3. Acknowledgements4. Table of contents5. List of figures6. List of tables7. List of abbreviations8. Introduction & objectives – the aims and objectives of your dissertationshould be at the end of your introduction chapter. 9.Methods & materials10. Results & discussions – if you wish, you may have your discussion ina separate chapter. 11. Conclusion12. References13. Appendices (if applicable)

Each of the above headings should begin on a new page.

Dissertation Format

1. The Dissertations for the MSc courses must be at least 15000 words (13000 –17000) excluding references. 2. Use a standard, easy-to-read word processor font such as Times or Arial.3. Font size 11 or 12.4. All pages should be numbered in the bottom right corner or bottom centre.5. Paragraphs should be made clearly visible by leaving an additional blank linebetween paragraphs. 6. Line spacing: 1.5 or double-spaced.7. Page alignment: justified8. Images and figures: please ensure that the images do not contain patientidentifiable information and that you have patients’ consent to the images. 9. References: We recommend that you follow the style for references accordingto the format of PRS or JPRAS. Please be accurate and consistent with your format.

Dissertation Marking Scheme††

†† Appendix 4

The dissertation will be double marked according to the marking scheme provided below in appendix 4.

Appendix 1

QMUL - MSc Aesthetic Medicine Guidelines for Dissertation - Systematic Reviews

Adapted from Mary Simons & Karen Marks of the Library Services, Macquarie University Sydney, Australia,

A systematic review is an overview of primary studies that used explicit and reproducible methods. Systematic reviews apply scientific strategies that limit bias by the systematic assembly, critical appraisal and synthesis of all relevant studies on a specific topic

A meta-analysis is a mathematical synthesis of the results of two or more primary studies that addressed the same hypothesis in the same way

Systematic reviews as well as meta-analyses of appropriate studies can be the best form of evidence available for health care practitioners

SYSTEMATIC REVIEW STEPS:

1. Research Question

2. Research Protocol

3. Literature Search

4. Data Extraction

5. Quality Appraisal

6. Data Analysis and Results

7. Interpretation of Results

1. Research QuestionThe first step in performing a systematic review is to formulate a primary research question as part of the research protocol. Appropriate questions to be addressed include: (1) phenomena associated with disease or interventions, (2) disease or condition frequency, (3) diagnostic accuracy, (4) disease etiology and/or risk factors, (5) prognosis, and (6) intervention effects. The aims of a systematic review can be varied and include: (1) clarifying the relative strengths and weaknesses of the literature on the question, (2) summarizing a large amount of literature, (3) resolving literature conflicts, (4) evaluating the need for a large clinical trial, (5) avoiding a redundant unnecessary trial, (6) increasing the statistical power of smaller studies, (7) improving the precision or identify a smaller treatment effect, and (8) improving the generalizability of treatment outcomes.

2. Research ProtocolOnce the research question is formulated, the research protocol is developed. The goal of developing a research protocol is to develop formulation of the questions and methods of the review before retrieving the literature. The methods for literature searching, screening, data extraction, and analysis should be contained in a written document to minimize bias before starting the literature search.

3. Literature SearchSources to search for studies for systematic reviews:

Cochrane Central Register of Controlled Trials (via Cochrane Library)

Cochrane Database of Systematic Reviews (via Cochrane Library)

Database of Abstracts of Reviews of Effects (DARE) database – ie: other reviews (via Cochrane Library)

Medline and Embase (Library does not subscribe to Embase)

Other databases, eg CINAHL, Scopus, PsycINFO

Journals

Conference proceedings

mailto:[email protected]

mailto:[email protected]

Bibliographies and references listed in primary sources

Unpublished and ongoing studies, including known experts in the field (seek by personal communication)

Raw data from published trials (seek by personal communication)

Foreign language literature (do not limit searches to English)

―Grey literature‖ (theses, internal reports, non peer-reviewed journals, pharmaceutical industry files)

PubMed Clinical Queries (www.ncbi.nlm.nih.gov/entrez/query ) includes search filters offering 4 categories of aetiology, prognosis, treatment, diagnosis, and choice of emphasizing sensitivity or specificity.

Cochrane Handbook appendix contains a list of approximately 30 clinical trials registries for finding unpublished primary studies (See Reference List for Library call number)

A minimum of two reviewers performs a first-stage screening of titles and abstracts based on the research question and its study design, population, intervention, and outcome to be studied. Based on the initial screening, selected full-text articles are obtained for the second-stage screening. Using the full text a second-stage screening is performed by at least two reviewers. The studies selected are then submitted for data extraction.

4. Data ExtractionA standardized form (paper or electronic) assists in the task of data extraction. For example:

Sample Data Extraction Form Items: Reference—including journal, title, author, volume in page numbers Objective—the study objective as stated by the authors Study design—type of trial Population—demographics of the participants in the study Intervention—description of the intervention Control—description of the control group or alternative intervention Outcome—results of the intervention and how measured including statistics used Comments—details regarding the study quality

5. Quality Appraisal A checklist to assess for biases is important: several quality scales and checklists have been developed for this. Each trial should be evaluated in terms of its:

Methodological quality—the extent to which the design and conduct are likely to have prevented systematic errors (bias)

Precision—a measure of the likelihood of random errors (usually depicted as the width of the confidence interval around the result)

External validity—the extent to which the results are generalisable or applicable to a particular target population

6. Data Analysis and ResultsAfter including and excluding studies based on the quality appraisal, data analysis and results of the studies should be undertaken. The initial step for this process involves a simple descriptive evaluation of each study, commonly presented in tabular format. Tables should include the population under study, the interventions, and outcomes.

7. Interpretation of ResultsMost of this information can be presented in the data analysis and results table in the manuscript. The strengths and weaknesses of the included studies must be discussed. Conclusions should be based on the best available scientific evidence. Recommendations regarding future studies can also be made.

PRISMA stands for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (www.prisma-statement.org). It is an evidence-based minimum set of items for reporting in systematic

http://www.ncbi.nlm.nih.gov/entrez/query

http://www.prisma-statement.org/

reviews and meta-analyses. PRISMA should be a helpful resource to improve reporting of systematic reviews and meta-analyses.

References used for this summary (all are available from the Library):

Wright, R. W., R. A. Brand, et al. (2007). "How to Write a Systematic Review." Clinical Orthopaedics and Related Research 455: 23-29

Systematic reviews in health care a practical guide / Paul Glasziou ... [et al.]. Cambridge ; New York : Cambridge University Press, 2001. eBook: Available via Library catalogue

Greenhalgh, T. (1997). "How to read a paper: Papers that summarise other papers (systematic reviews and meta-analyses)." BMJ 315(7109): 672-675.

Oxman, A. D. (1994). "Systematic Reviews: Checklists for review articles." BMJ 309(6955): 648-651.

Systematic reviews and meta-analysis /Julia H. Littell, Jacqueline Corcoran, Vijayan Pillai. Series Title: Pocket guides to social work research methods Oxford ;New York : Oxford University Press. Available in Library: H62 .L497 2008

Harvey, R. (2007). "Systematic review as a primer rather than endpoint for clinical research: The training perspective." Otolaryngology-Head and Neck Surgery 137(4): S66-S68.

Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). ―Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement‖. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097

Cochrane handbook for systematic reviews of interventions / edited by Julian P.T. Higgins Chichester, England ; Hoboken, NJ : Wiley-Blackwell and Sally Green., c2008. Available in Library: R723.7 .C63 2008

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000097

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000097

http://voyager.mq.edu.au/vwebv/search?searchArg=%20R723.7%20.C63%202008&searchCode=CALL%2B&searchType=1

http://voyager.mq.edu.au/vwebv/search?searchArg=%20R723.7%20.C63%202008&searchCode=CALL%2B&searchType=1

CASE-CONTROL (INCLUDING HARM) CHECKLIST

How do you rate this paper? 1 2 3 4 5 6 7 8 9 10

1.0 OBJECTIVES AND HYPOTHESES

1.1 Are the objectives of the study clearly stated?

2.0 DESIGN

2.1 Is the study design suitable for theobjectives?

2.2 Who/what was studied?

2.3 Was this the right sample to answer theobjectives?

2.4 Did this include a clearly identifiedcomparison group, identical in allaspects other than the exposure?

2.5 Did the exposure precede outcome?

2.6 Is the study large enough to achieve itsobjectives? Have sample size estimatesbeen performed?

2.7 Were all subjects accounted for?

2.8 Were all appropriate outcomesconsidered?

2.9 Has ethical approval been obtained ifappropriate?

Appendix 2 A

3.0 MEASUREMENT AND OBSERVATION

3.1 Is it clear what was measured, how it wasmeasured and what the outcomes were?

3.2 Were the exposures to the agent andoutcomes measured in the same wayin all of the groups compared?

3.3 Were the assessments of exposureblinded to outcome?

3.4 Was follow up sufficiently long andcomplete?

3.5 Are the measurements valid?

3.6 Are the measurements reliable?

3.7 Are the measurements reproducible?

4.0 PRESENTATION OF RESULTS

4.1 Are the basic data adequately described?

4.2 Are the results presented clearly,objectively and in sufficient detail toenable readers to make their ownjudgement?

4.3 Can you construct a 2x2 table ofexposure and outcome?

4.4 Was there a dose response effect?

4.5 Are the results internally consistent, i.e.do the numbers add up properly?

5.0 ANALYSIS

5.1 Are the data suitable for analysis?

5.2 Are the methods appropriate to the data?

5.3 Are any statistics correctly performed andinterpreted?

5.4 Are relative risks or odds presentedwith confidence intervals?

6.0 DISCUSSION

6.1 Are the results discussed in relation toexisting knowledge on the subject andstudy objectives?

6.2 Is a causal relationship betweenexposure and outcome suggested?

6.3 If so, is this causal relationshipjustified?

6.4 Is the discussion biased?

7.0 INTERPRETATION

7.1 Are the authors’ conclusions justified bythe data?

7.2 What level of evidence has this paperpresented? (using CEBM levels)

7.3 Does this paper help me answer myproblem?

How do you rate this paper now? 1 2 3 4 5 6 7 8 9 10

In addition, answer the following questions with regards to local practice.

8.0 IMPLEMENTATION

8.1 Can any necessary change beimplemented in practice?

8.2 What aids to implementation exist?

8.3 What barriers to implementation exist?

COHORT CHECKLIST




2.0 DESIGN



2.3 Was a control group used ifappropriate?

2.4 Were outcomes defined at the start ofthe study?






Appendix 2 B



3.2 Was the assessment of outcomesblinded?

3.3 Was follow up sufficiently long andcomplete?







4.3 How large are the effects within aspecified time?


5.0 ANALYSIS




6.0 DISCUSSION



7.0 INTERPRETATION






8.0 Implementation



8.3 What barriers to implementation exist

8.4 Are the study patients similar to yourown?

8.5 Does the paper give any conclusionsthat will affect what you will offer ortell your patient?

ECONOMIC CHECKLIST




2.0 DESIGN








2.8 Does this economic analysis cite validevidence on the clinical efficacy of thealternative?

2.9 From who’s perspective were costsmeasured?

2.10 Are all costs and effects identified?

Appendix 2 C



3.2 Were consequences and costsmeasured accurately in appropriateunits?

3.3 Were opportunity costs measured?








5.0 ANALYSIS




6.0 DISCUSSION



6.3 Has a sensitivity analysis beenperformed (was appropriate allowancemade for uncertainties)?

7.0 INTERPRETATION






8.0 IMPLEMENTATION



8.3 What barriers to implementation exist?

8.4 Do the costs apply in my practice?

8.5 Are the treatments likely to beeffective in my setting?

Five steps to conducting a systematic reviewKhalid S Khan MB MSc Regina Kunz MD MSc1 Jos Kleijnen MD PhD2 Gerd Antes PhD3

J R Soc Med 2003;96:118–121

Systematic reviews and meta-analyses are a key element ofevidence-based healthcare, yet they remain in some waysmysterious. Why did the authors select certain studies andreject others? What did they do to pool results? How did abunch of insignificant findings suddenly become significant?This paper, along with a book1 that goes into more detail,demystifies these and other related intrigues.

A review earns the adjective systematic if it is based on aclearly formulated question, identifies relevant studies,appraises their quality and summarizes the evidence by useof explicit methodology. It is the explicit and systematicapproach that distinguishes systematic reviews fromtraditional reviews and commentaries. Whenever we usethe term review in this paper it will mean a systematic review.Reviews should never be done in any other way.

In this paper we provide a step-by-step explanation—there are just five steps—of the methods behind reviewing,and the quality elements inherent in each step (Box 1). Forpurposes of illustration we use a published reviewconcerning the safety of public water fluoridation, but wemust emphasize that our subject is review methodology, notfluoridation.

EXAMPLE: SAFETY OF PUBLIC WATERFLUORIDATION

You are a public health professional in a locality that haspublic water fluoridation. For many years, your colleaguesand you have believed that it improves dental health.Recently there has been pressure from various interestgroups to consider the safety of this public health interventionbecause they fear that it is causing cancer. Public healthdecisions have been based on professional judgment andpractical feasibility without explicit consideration of thescientific evidence. (This was yesterday; today the evidence isavailable in a York review2,3, identifiable on MEDLINEthrough the freely accessible PubMed clinical queriesinterface [http://www.ncbi.nlm.nib.gov/entrez/query/static/clinical.html], under ‘systematic reviews’.)

STEP 1: FRAMING THE QUESTION

The research question may initially be stated as a query infree form but reviewers prefer to pose it in a structured andexplicit way. The relations between various components of

118

J O U R N A L O F T H E R O Y A L S O C I E T Y O F M E D I C I N E V o l u m e 9 6 M a r c h 2 0 0 3

Education Resource Centre, Birmingham Women’s Hospital, Birmingham B15

2TG, UK; 1German Cochrane Centre, Freiburg and Department of Nephrology,

Charite, Berlin, Germany; 2Centre for Reviews and Dissemination, York, UK;3German Cochrane Centre, Freiburg, Germany

Correspondence to: Khalid S Khan

E-mail: [email protected]

Step 1: Framing questions for a review

The problems to be addressed by the review should be

specified in the form of clear, unambiguous and structured

questions before beginning the review work. Once the review

questions have been set, modifications to the protocol should

be allowed only if alternative ways of defining the populations,

interventions, outcomes or study designs become apparent

Step 2: Identifying relevant work

The search for studies should be extensive. Multiple resources

(both computerized and printed) should be searched without

language restrictions. The study selection criteria should flow

directly from the review questions and be specified a priori.

Reasons for inclusion and exclusion should be recorded

Step 3: Assessing the quality of studies

Study quality assessment is relevant to every step of a review.

Question formulation (Step 1) and study selection criteria (Step

2) should describe the minimum acceptable level of design.

Selected studies should be subjected to a more refined quality

assessment by use of general critical appraisal guides and

design-based quality checklists (Step 3). These detailed

quality assessments will be used for exploring heterogeneity

and informing decisions regarding suitability of meta-analysis

(Step 4). In addition they help in assessing the strength of

inferences and making recommendations for future research

(Step 5)

Step 4: Summarizing the evidence

Data synthesis consists of tabulation of study characteristics,

quality and effects as well as use of statistical methods for

exploring differences between studies and combining their

effects (meta-analysis). Exploration of heterogeneity and its

sources should be planned in advance (Step 3). If an overall

meta-analysis cannot be done, subgroup meta-analysis may

be feasible

Step 5: Interpreting the findings

The issues highlighted in each of the four steps above should

be met. The risk of publication bias and related biases should

be explored. Exploration for heterogeneity should help

determine whether the overall summary can be trusted, and, if

not, the effects observed in high-quality studies should be

used for generating inferences. Any recommendations should

be graded by reference to the strengths and weaknesses of

the evidence

Box 1 The steps in a systematic review

AMG

Typewritten Text

Appendix 3

the question and the structure of the research design areshown in Figure 1. This paper focuses only on the questionof safety related to the outcomes described below.

Free-form question

Is it safe to provide population-wide drinking waterfluoridation to prevent caries?

Structured question

. The populations—Populations receiving drinking watersourced through a public water supply

. The interventions or exposures—Fluoridation of drinkingwater (natural or artificial) compared with non-fluoridated water

. The outcomes—Cancer is the main outcome of interestfor the debate in your health authority

. The study designs—Comparative studies of any designexamining the harmful outcomes in at least twopopulation groups, one with fluoridated drinking waterand the other without. Harmful outcomes can be rareand they may develop over a long time. There areconsiderable difficulties in designing and conductingsafety studies to capture these outcomes, since a largenumber of people need to be observed over a longperiod. These circumstances demand observational, notrandomized studies. With this background, systematicreviews on safety have to include evidence from studieswith a range of designs.

STEP 2: IDENTIFYING RELEVANT PUBLICATIONS

To capture as many relevant citations as possible, a widerange of medical, environmental and scientific databaseswere searched to identify primary studies of the effects of 119


Figure 1 Structured questions for systematic reviews and relations between question components in a comparative study

water fluoridation. The electronic searches were supple-mented by hand searching of Index Medicus and ExcerptaMedica back to 1945. Furthermore, various internet engineswere searched for web pages that might provide references.This effort resulted in 3246 citations from which relevantstudies were selected for the review. Their potentialrelevance was examined, and 2511 citations were excludedas irrelevant. The full papers of the remaining 735 citationswere assessed to select those primary studies in man thatdirectly related to fluoride in drinking water supplies,comparing at least two groups. These criteria excluded 481studies and left 254 in the review. They came from thirtycountries, published in fourteen languages between 1939and 2000. Of these studies 175 were relevant to thequestion of safety, of which 26 used cancer as an outcome.

STEP 3: ASSESSING STUDY QUALITY

Design threshold for study selection

Adequate study design as a marker of quality, is listed as aninclusion criterion in Box 1. This approach is mostapplicable when the main source of evidence is randomizedstudies. However, randomized studies are almost impos-sible to conduct at community level for a public healthintervention such as water fluoridation. Thus, systematicreviews assessing the safety of such interventions have toinclude evidence from a broader range of study designs.Consideration of the type and amount of research likely tobe available led to inclusion of comparative studies of anydesign. In this way, selected studies provided informationabout the harmful effects of exposure to fluoridated watercompared with non-exposure.

Quality assessment of safety studies

After studies of an acceptable design have been selected,their in-depth assessment for the risk of various biasesallows us to gauge the quality of the evidence in a morerefined way. Biases either exaggerate or underestimate the‘true’ effect of an exposure. The objective of the includedstudies was to compare groups exposed to fluoridated

drinking water and those without such exposure for rates ofundesirable outcomes, without bias. Safety studies shouldascertain exposures and outcomes in such a way that the riskof misclassification is minimized. The exposure is likely tobe more accurately ascertained if the study was prospectiverather than retrospective and if it was started soon afterwater fluoridation rather than later. The outcomes of thosedeveloping cancer (and remaining free of cancer) are likelyto be more accurately ascertained if the follow-up was longand if the assessment was blind to exposure status.

When examining how the effect of exposure onoutcome was established, reviewers assessed whether thecomparison groups were similar in all respects other thantheir exposure to fluoridated water. This is because theother differences may be related to the outcomes of interestindependent of the drinking-water fluoridation, and thiswould bias the comparison. For example, if the peopleexposed to fluoridated water had other risk factors thatmade them more prone to have cancer, the apparentassociation between exposure and outcome might beexplained by the more frequent occurrence of these factorsamong the exposed group. The technical word for suchdefects is confounding. In a randomized study, confoundingfactors are expected to be roughly equally distributedbetween groups. In observational studies their distributionmay be unequal. Primary researchers can statistically adjustfor these differences, when estimating the effect ofexposure on outcomes, by use of multivariable modelling.

Put simply, use of a prospective design, robustascertainment of exposure and outcomes, and control forconfounding are the generic issues one would look for inquality assessment of studies on safety. Consequently,studies may range from satisfactorily meeting qualitycriteria, to having some deficiencies, to not meeting thecriteria at all, and they can be assigned to one of threeprespecified quality categories as shown in Table 1. Aquality hierarchy can then be developed, based on thedegree to which studies comply with the criteria. None ofthe studies on cancer were in the high-quality category, butthis was because randomized studies were non-existent and120


Table 1 Description of quality assessment of studies on safety of public water fluoridation

Quality categories High Moderate Low

Prospective design Prospective Prospective Prospective or retrospective

Ascertainment of exposure Study began within 1 year of

fluoridation

Study began within 3 years

of fluoridation

Study began 43 years after

fluoridation

Ascertainment of outcome Follow-up for at least 5 years

and blind assessment

Long follow-up and blind

assessment

Short follow-up and unblinded

assessment

Control for confounding Adjustment for at least three

confounding factors (or use

of randomization)

Adjustment for at least one

confounding factor

No adjustment for confounding

factors

control for confounding was not always ideal in theobservational studies. There were 8 studies of moderatequality and 18 of low quality.

STEP 4: SUMMARIZING THE EVIDENCE

To summarize the evidence from studies of variable designand quality is not easy. The original review3 provides detailsof how the differences between study results wereinvestigated and how they were summarized (with orwithout meta-analysis). This paper restricts itself tosummarizing the findings narratively. The associationbetween exposure to fluoridated water and cancer ingeneral was examined in 26 studies. Of these, 10 examinedall-cause cancer incidence or mortality, in 22 analyses. Ofthese, 11 analyses found a negative association (fewercancers due to exposure), 9 found a positive one and 2found no association. Only 2 studies reported statisticallysignificant differences. Thus no clear association betweenwater fluoridation and increased cancer incidence ormortality was apparent. Bone/joint and thyroid cancerswere of particular concern because of fluoride uptake bythese organs. Neither the 6 studies of osteosarcoma nor the2 studies of thyroid cancer and water fluoridation revealedsignificant differences. Overall no association was detectedbetween water fluoridation and mortality from any cancer.These findings were also borne out in the moderate-qualitysubgroup of studies.

STEP 5: INTERPRETING THE FINDINGS

In the fluoridation example, the focus was on the safety of acommunity-based public health intervention. The generallylow quality of available studies means that the results mustbe interpreted with caution. However, the elaborate effortsin searching an unusually large number of databases providesome safeguard against missing relevant studies. Thus theevidence summarized in this review is likely to be as good asit will get in the foreseeable future. Cancer was the harmfuloutcome of most interest in this instance. No associationwas found between exposure to fluoridated water andspecific cancers or all cancers. The interpretation of theresults may be generally limited because of the low qualityof studies, but the findings for the cancer outcomes aresupported by the moderate-quality studies.

RESOLUTION

After having spent some time reading and understanding thereview, you are impressed by the sheer amount of published

work relevant to the question of safety. However, you aresomewhat disappointed by the poor quality of the primarystudies. Of course, examination of safety only makes sensein a context where the intervention has some beneficialeffect. Benefit and harm have to be compared to provide thebasis for decision making. On the issue of the beneficialeffect of public water fluoridation, the review3 reassuresyou that the health authority was correct in judging thatfluoridation of drinking water prevents caries. From thereview you also discovered that dental fluorosis (mottledteeth) was related to concentration of fluoride. When theinterest groups raise the issue of safety again, you will beable to declare that there is no evidence to link cancer withdrinking-water fluoridation; however, you will have tocome clean about the risk of dental fluorosis, which appearsto be dose dependent, and you may want to measure thefluoride concentration in the water supply and share thisinformation with the interest groups.

The ability to quantify the safety concerns of yourpopulation through a review, albeit from studies ofmoderate to low quality, allows your health authority, thepoliticians and the public to consider the balance betweenbeneficial and harmful effects of water fluoridation. Thosewho see the prevention of caries as of primary importancewill favour fluoridation. Others, worried about thedisfigurement of mottled teeth, may prefer other meansof fluoride administration or even occasional treatment fordental caries. Whatever the opinions on this matter, you areable to reassure all parties that there is no evidence thatfluoridation of drinking water increases the risk of cancer.

CONCLUSION

With increasing focus on generating guidance andrecommendations for practice through systematic reviews,healthcare professionals need to understand the principles ofpreparing such reviews. Here we have provided a briefstep-by-step explanation of the principles. Our book1

describes them in detail.

REFERENCES

1 Khan KS, Kunz R, Kleijnen J, Antes G. Systematic Reviews to SupportEvidence-Based Medicine. How to Review and Apply findings of Health CareResearch. London: RSM Press, 2003

2 McDonagh M, Whiting P, Bradley M, et al. Systematic review of waterfluoridation. BMJ 2000;321:855–9

3 NHS Centre for Reviews and Dissemination (CRD). A systematicreview of water fluoridation. CRD Report 18. York: University of York,2000 [http://www.york.ac.uk/inst/crd/fluorid.htm]

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Marking Scheme

Grade A (70%+) Grade B (60 - 70%) Grade C (50 – 60%)Approach 10% Original approach

Shows critical insightAppliesmodels/tests/techniquessuccessfully

Appropriate application ofmodels/tests/techniques

Partially successful atapplication ofmodels/tests/techniques

Contents 50% Taught course material as astarting pointAdvanced comprehensionAwareness of complex issuesExtensive literature review

Taught course material appliedAdequate comprehensionAdequate awareness of issuesComprehensive literaturereview

Taught course material usedEvidence of comprehensionSome gapsCovers the literature

Analysis 10% Original analysisCompares dataAnalytical insight

Appropriate analysis Attempts analysisSome misconception

Conclusion 10% Relevant, valid, appropriateCritically evaluatedOffers a realistic vision orrecommendation for the future

Relevant, valid, appropriate Some relevant and validconclusions

References 10% All work referencedAccurate references

Present but incompleteAccurate references

Some references

Presentation and style10%

InnovativeWell organised and structuredConsistent formatCaptures and maintains readers’attentionMinimal or no error

AppropriateOrganised and structuredA few inconsistencies withformattingMaking sense for readers

AppropriateSome structureNumerous inconsistencies withformatting

Finally, YOU ARE REMINDED THAT PLASGIARISM IS STRICTLY FORBIDDEN! Please refer to the section“Plagiarism and TURNITIN” prior to your submission. You are advised to begin your work on the dissertationwell in advance to ensure your dissertation is completed and submitted before the deadline.

Good Luck!

AMG

Typewritten Text

Appendix 4

dissertation guidelines

Documents