EBM Manual

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL

A MANUAL FOR TRAINERS AND EVIDENCE SEEKERS 1

2 nd E D I T I O N

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

INTRODUCTION

INTRODUCTION

A Message from the NOME

Develop a passion for Education. If you do, it will never

.”cease to grow We have found our passion in medical education where SCOME gave us the tools not only to start asking the right .questions but also to take actions to make a change I’m Mahmoud Nassar, IFMSA-EGYPT NOME for term 20192020, and on behalf of my national team, we are presenting to you this series of manuals which aims to educate different medical students in medical education topics and promote our latest activities we are doing for a better development of .medical education in Egypt In addition, those manuals would be the gate to IFMSA and non-IFMSA medical students to know more about our medical education projects and bring them closer to the work and activities that enormous NGOs as IFMSA-Egypt are initiating to improve the quality of future health professionals in the .fields of public health and medical education I would like to thank everyone who worked and contributed to this marvellous work which would stand for the upcoming years as a reference to come back while looking for a credible ,and comprehensive resource for topics as First-Aid .Evidence-Based-Medicine, or Medical Education topics

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Mahmoud A. Nassar

A Message from the Manual Team

A 21-st century clinician who cannot critically read a study is as unprepared as one who cannot take a blood pressure or examine the cardiovascular system” —Paul Glaszio, (BMJ 2008:337:704705

Congratulations on taking the first step in the journey to EvidenceBased Medicine (EBM) and its impact on medical practice and public health. EBM is the conscientious, explicit, judicious, and reasonable use of modern, best evidence in making decisions about the care of individual patients. A good physician is the one who integrates clinical experience and patient values with the best available research to eliminate malpractice and produce a healthier community with more professional future physicians and researchers Ignoring evidence leads to avoidable harm, and failing to admit“ our uncertainties means we don’t get better evidence” —Margaret McCartney In this manual you’ll learn all the evidence based medicine basics and how to apply and explain them to others, thus helping in creating a more knowledgeable, healthier, and aware community.

This manual is designed for all trainers and evidence seekers out there, supplied with examples and activities to help connect different ideas and perspectives better and ensure understanding the core concepts and their applications by the end of your session.

This manual breaks up EBM into 5 core chapters and by the end of this manual you should be able to understand and explain all the .topics covered and apply them in your future

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

INTRODUCTION

INTRODUCTION

04 08

Introduction

Chapter 1

Evidence-Based Medicine

Map Of Contents 14

Chapter 2

Study Design

The IFMSA was founded in 1951 in Copenhagen as a result of the postwar wave of friendship among international students and has evolved to represent more than One Million medical students from all continents .and over 123 nations The IFMSA is affiliated to the United Nations system as a non-political and non- governmental organization, and is recognized by the World Health Organization as the official .international forum for medical students since 1969 Since 1951, IFMSA exists to serve as a forum for sharing ideas and expertise among medical student organizations pertaining to public health, medical education, reproductive health and human rights. IFMSA also serves as an action platform to formulate policies and co-ordinate activities by its member .organizations IFMSA aims to serve medical students all over the world through its member organizations, to promote and facilitate international cooperation in professional training and to contribute to the development .of culturally aware and socially responsible physicians

36 Chapter 3 Chapter 4

48

Critical Appraisal

5

Statistics

Chapter 5

54

Scientific Writing

IFMSA-Egypt is a full member of the International Federation of Medical Students’ Association (IFMSA) which is the only official body of medical students worldwide made up of 123 countries spanning all continents. It is a Non-Governmental Association related to the World Health Organization, recognized as WHO IFMSA-Egypt is represented by medical students from a .wide range of medical schools all over Egypt IFMSA-Egypt consists of 25 Local Committees in all medical .schools around Egypt

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EVIDENCE-BASED EVIDENCE-BASED MEDICINE MEDICINE MANUAL MANUALIFMSA-EGYPT IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

NARRATOR MESSAGE

INTRODUCTION

Narrator: Hello reader, in this book, you will know about the mystery of Evidence-Based Medicine and some of the research science, but before that I will tell you a concise story. Once upon a time in a small village, there was a farmer called Omar. He was a hardworking person who was devoted to his job tremendusoly. However, he loved eating more, he could eat the proportions of two persons combined, but little did he know that this habit will turn against him sooner or later.

One day after a difficult day on the farm, Omar›s cousin, Ali invited him to have lunch with his family, so they went together to Ali’s house and had a delicious meal. After they have finished, Ali asked his son Tarek to make them two cups of tea, but right then, Omar palced his hand on his stomach and started to scream loudly out of agony. Ali and his son Tarek were perplexed and tried to soothe Omar, but he did not stop screaming. Tarek told his father to fetch him some milk as they do traditionally, but when Omar drank the milk, his pain become worsened, so Ali took him quickly to the village’s doctor.

The doctor examined Omar and asked Ali to narrate what happened, after hearing the story, the doctor told them that Omar has a stomach germ, as well as ulcers in the stomach, so giving Omar milk was an unwise decision . He advised them not to depend on traditional medicine and to always ask a doctor who’s updated with the recent knowledge of medicine and gave Omar some medicine to help him with his condtion.

After this astonishing story, let’s begin our journey to discover the secrets of EBM. ☑☑

WHAT IS EVIDENCE-BASED MEDICINE?

Evidence-based medicine (EBM) is the conscientious, explicit, judicious and reasonable use of modern, best evidence in making decisions about the care of individual patients. EBM integrates clinical experience and patient values with the best available research information. It is a movement that aims to increase the use of high-quality clinical research in clinical decision making.

EBM requires new skills of the clinician, including efficient literature searching, and the application of formal rules of evidence in evaluating the clinical literature.

The practice of evidence-based medicine is a process of lifelong, self-directed, problem-based learning in which caring for one’s patients creates the need for clinically important information about a diagnosis, prognosis, therapy, and other clinical and health care issues. It is not a “cookbook” with recipes, but its good application brings cost-effective and better health care.

One of the greatest achievements of evidence-based medicine has been the development of systematic reviews and meta-analyses, methods by which researchers identify multiple studies on a topic, separate the best ones and then critically analyze them to come up with a summary of the best available evidence.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

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EVIDENCE BASED MEDICINE

Evidencebasedmedicine

The EBM-oriented clinicians of tomorrow have three tasks: a) to use evidence summaries in clinical practice; b) to help develop and update selected systematic reviews or evidence-based guidelines in their area of expertise; and c) to enroll patients in studies of treatment, diagnosis, and prognosis on which medical practice is based.

WHAT’S THE ORIGIN OF EBM? It can be traced back to the late 1980s or even earlier when in 1970 a committee of physicians and administrators tried to evaluate literature to understand how health professionals learn and keep up to date after they graduate.

Clinical Expertise

Best Evidence EBM

Patient Values

STEP 5 STEP 4 STEP 3 STEP 2 STEP 1 Ask a clinical question

9

Acquire the best evidence

Appraise the evidence

Apply the evidence

Assess your performance

Chapter 1 Evidence-based medicine 8

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE BASED MEDICINE

Evidencebasedmedicine

ARE THOSE THE ONLY REASONS WHY I SHOULD DEPEND ON RECENT RESEARCH PAPERS? No, the main purpose of any research paper is that it has sharp rules to be approved and accepted, and these rules guard the paper against having any defects or bias. As we said before, “research papers” are the main source for EBM. The main thing to remember with any research paper is that it is based on an hourglass structure. It begins with general information and undertaking. As you a literature review. It becomes more nail down, specific a research problem and hypothesis. Finally; it again becomes more general as you try to apply yours. ☑☑

PICO SEARCH STRATEGY:

Clinical guidelines Meta-analysis and systematic reviews

Randomized controlled trials prospective, test treatment

It is common that outcome terms are not often mentioned in the subject headings or abstracts of database records. Consequently, ‘outcome’ terms are often omitted from the search strategy.

Cohort studies Prospective: cohort has been exposed to a risk, observe for outcome of interest

1. The patient or problem – who are the relevant patients, what kind of problem are we trying to

solve?

2. The intervention – what is the management strategy, diagnostic test, or exposure? (drugs, di-

agnostic tests, foods, or surgical procedures).

3. Comparison of interventions – what is the control or alternative management strategy, test, or

Case-controlled studies Retrospective: subjects have the outcome of interest, looking for risk factor Caase reports or case series Narrative Reviews, Expert Opinions, Editorials Animal and laboratory studies

Observational studies

Primary studies

The PICO framework can be used to construct the terms for your search strategy. In other words, the framework can be used to devise the search terms for the population, which can be combined with search terms related to the intervention(s) and comparison(s) (if there are any).

PICO FORMAT:

Secondary pre appraised, or filtered studies

No design

Not involved with humand

exposure that we will compare?

4. The outcome – what are the patient-relevant consequences of the exposure in which we are

interested?

Patient population Intervention or issue

Example: The Evidence-Based Medicine Pyramid is simply a diagram that was created to help us understand how to weigh different levels of evidence to make health-related decisions. It helps us put the results of each study design into perspective, based on the relative strengths and weaknesses of each design. Each ascending level represents a different type of study design and corresponds to increasing rigor, quality, and reliability of the evidence.

Medical practitioners simply cannot keep up with reading all the literature because they are overloaded with information. In fact, for a primary care physician to stay up to date, they’d need to read 17 articles a day, 365 days a year. Which is an impossible task, but evidence-based medicine offers clinicians a way to stay current with best practices using standardized, evidence-based protocols.

Comparison intervention (optional) Outcome of interest

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

ACTIVITY

EVIDENCE BASED MEDICINE

✅✅ Example: John, 31 years old, was diagnosed with heart failure 3 years old and prescribed a be-

ta-blocker which dramatically improved his symptoms. John’s 5-year-old daughter, Sarah, has been recently diagnosed with chronic symptomatic congestive heart failure. John asks you, Sarah’s pediatrician, whether his daughter should also be prescribed a beta-blocker.

Is there a role for beta-blockers in the management of heart failure in children?

1. Patient problem: Children with congestive heart failure.

2. Intervention: Carvedilol.

3. Comparison: No carvedilol.

4. Outcome: Improvement of congestive heart failure symptoms. ✅✅ Another example: A 30-year-old male is diagnosed with depression. He would prefer to try

alternative medicine rather than SSRI. You believe that SSRI would improve his disorder, but he wants to know if ST. John›s Wart would be just as effective for reducing symptoms.

Concepts to search: 1. P: Depression.

2. I: SSRIs. 3. C: ST. John’s Wart.

4. O: Reduced depression symptoms.

☑☑

TRADITIONAL MEDICINE

Traditional medicine as defined by the World Health Organization is the total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement, or treatment of physical and mental illness. Some traditional medicine systems are supported by huge volumes of literature and records of the theoretical concepts and practical skills; others pass down from generation to generation through verbal teaching. To date, in some parts of the world, the majority of the population continues to rely on their own traditional medicine to meet their primary health care needs. When adopted outside of its traditional culture, traditional medicine is often referred to as «complementary and alternative medicine.»

Among others, the most widely used traditional medicine systems today include those of China, India, and Africa. In this chapter, the Chinese, Indian, and African systems of traditional medicine are described.

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☑☑

ACTIVITY (1) FOR EBM PYRAMID

Write the EBM pyramid elements on two sets of different colored sticky notes and hide them in different parts of your session’s room (it is preferred to do this before the beginning of the session). Then divide your audience into two groups. Each group receives one color of the two, then ask the two groups to find their hidden sticky notes before the other team does. The team that finishes first, is then asked to order the elements of the pyramid, and the second team follows after finding their sticky notes. Finally, the team who finds and orders the notes faster and more accurately wins. ☑☑

ACTIVITY (2) FOR PICO

Divide the audience into two groups and give each group 4 papers of PICO research strategy elements, then ask them to order the papers. The fastest and the most accurate group is the winner.

EVIDENCE-BASED EVIDENCE-BASED MEDICINE MEDICINE MANUAL MANUALIFMSA-EGYPT IFMSA-EGYPT

STUDY DESIGNS

☑☑

INTRODUCTION

During your venture as an EBM trainer/enthusiast, you must be equipped with the power of identifying the study design of the research paper you are reading.

This is especially important for us as EBM trainers or future physicians to be able to determine the validity of each evidence.

Being familiar with the different study designs, particularly with the advantages, disadvantages, purpose, and meaning of each design is also very helpful during searching the databases for an answer to a clinical question. ☑☑

TYPES OF RESEARCH

There are two types of research in medicine: 1. Primary Research 2. Secondary research

Original data collector

Primary Research

Secondary research

The author of the research is the source of the data.

The author summarizes the data from already published papers (data is from other mul�ple papers).

Examples

☑☑

• •

Observa�onal studies Experimental studies

• •

Systematic review and meta-analysis Literature review

PRIMARY RESEARCH STUDY DESIGNS

Research

Primary

Diagnos�c

Non-RCTs

study designs

Observa�onal

Interven�onal

RCT

Descrip�ve

Descrip�ve

15

Chapter 2

Secondary

Analy�cal

Analy�cal

Descrip�ve

Analy�cal

Analy�cal

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

STUDY DESIGNS

ACTIVITY Secondary pre appraised, or filtered studies

Clinical guidelines

☑☑

Meta-analysis and systematic reviews

Cohort studies Prospective: cohort has been exposed to a risk, observe for outcome of interest Case-controlled studies Retrospective: subjects have the outcome of interest, looking for risk factor Caase reports or case series Narrative Reviews, Expert Opinions, Editorials Animal and laboratory studies

**

Observational studies

Primary studies

Randomized controlled trials prospective, test treatment

No design

Not involved with humand

OBSERVATIONAL STUDIES

An observational study is when the investigator “observes” the subjects of the study, collecting data on exposure and outcomes without any intervention in the study.

Advantages

Limita�ons

The researcher “the observer” has little control over the environment, this means: It is better than interven�onal studies in evaluating drug efficacy in real life, without any factors that might affect the result of the research.

It is harder to determine a causal rela�onship by an observa�onal study because other factors may have interfered and led to the results.

Example: A group of people who might volunteer for an experimental study will be more likely to adhere to the drug.

It is more useful when the interven�on is unethical.

It tends to be long and expensive.

Example: Testing whether exposure radiation has a bad effect on health or not.

It can be the first step in an experimental study "observa�on leading to clinical trial".

It’s harder to determine whether the rela�onship between X and Y is an associa�on or causa�on.

Example: A Polish physician had proposed that rickets is linked to the new lifestyle of staying indoors, and suggested exposure to fresh air and sunlight to cure the disease.

Example: This Polish physician could have proposed the complete opposite (that children who have rickets are more likely to stay indoors because of limb deformities) and still, it could have been plausible.

In another word, observa�onal studies help determine an associa�on between X and Y but not necessarily that X caused Y.

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ACTIVITY (1) FOR INTRODUCTION

You can ask the participant on why it is important for all physicians, not only people who are interested in research, to be able to identify different study designs. ☑☑

ACTIVITIES (2),(3) FOR “TYPES OF RESEARCH”

✅✅ You can ask the participants what is the meaning of primary research and sec-

ondary research.

✅✅ Where does it belong”: You can put stickers with (primary research) vs (second-

ary research). Then you write each of the elements of the comparison between primary research and secondary research on sticky notes/pieces of papers and ask participants to put each point under either primary research or secondary research and then then you ask the participants why they made this choice.

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED EVIDENCE-BASED MEDICINE MEDICINE MANUAL MANUALIFMSA-EGYPT IFMSA-EGYPT

STUDY DESIGNS

Study Designs

Importance

Limita�ons

Used to measure the prevalence of a certain condi�on in a target popula�on.

Cannot be used to measure the incidence of a disease. (Check chapter x for incidence and prevalence.)

Can be used to determine the associa�on between variables in a target popula�on.

Cannot be used to determine a cause-effect rela�onship (because the timeframe is a single point, so you don’t know what happened first).

Note: You have to remember, studying advantages and disadvantages of each study design does not mean that there is a good study design and a bad study design, but rather this should contribute to understanding the essence of each study design. Thus, when working on the research you know which study design to choose according to the situation and research question, and when you are an EBM-er, you know which study design will answer your question.

Observational studies include (Figure 1: Study designs): ✅✅ Descriptive studies

Example: A cross-sectional study (NHANES III)

found out that there is an association between obesity in childhood and increased hours spent in front of the television. Now, do the children stay in front of the television because they are obese and it is harder for them to move? Or is it the opposite?

Because this type of study design depends on collecting data at a single point in time, it has some advantages of being: • • • •

1. Case report 2. Case series 3. Cross-sectional ✅✅ Analytical studies

Cannot be used to study a rare disease.

1. Cross-sectional

Cheap Inexpensive Less time consuming (you don't have to wait for the outcome to happen) No loss of follow-up because of no followup

2. Cohort 3. Case-control

**

CROSS-SECTIONAL STUDIES

Definition: A cross-sectional study is the type of study design where the investigator collects data from the target population at a single point of time (like a snapshot).

ANALYSIS: Prevalence is the burden of a disease in a specific population at a specific point in time.

It can be calculated by the following formula:

Past

Prevalence Rate =

Total number of cases of a diease at a given timeIndcidence

x 100

Present

Future

Cross-sectional study

Total population at risk during the a given time

Prospective Cohort study

Retrospective Cohort study

INCIDENCE

MORTALITY

19

Case control study

PREVALENCE

CURE

Randomized controlled trial

Time

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED EVIDENCE-BASED MEDICINE MEDICINE MANUAL MANUALIFMSA-EGYPT IFMSA-EGYPT

STUDY DESIGN

Study Designs

**

✅✅ IMPORTANCE: 1. Cohort studies are important to determine an association between a risk factor and an out-

come condition or a disease.

CASE REPORT AND CASE SERIES

Definition: A case report is a study used in reporting a rare or unique condition. While the case series describes multiple unique cases.

2. They are of special value when the exposure is rare. Or when it’s unethical to expose the target

population to the risk factor we are studying, like investigating whether smoking can cause lung cancer or not. (it’s unethical to assign a group to smoke for example to investigate lung cancer risk).

3. Unlike cross-sectional studies, cohort studies can be used to measure the incidence of a dis-

ease in a population.

Importance

Limita�ons

This type of study design is performed to describe a new disease.

At the bo�om of the evidence pyramid

A unique manifesta�on of a known disease.

The chosen case does not represent the popula�on, so no generalizable findings.

An unreported drug side effect.

Cannot determine a cause-effect rela�onship.

4. They are better than case-control studies (Figure 2).

5. Because the timeline is clear (we start with exposure and go to the outcome) this prevents re-

verse causality (unlike in cross-sectional studies).

Unique therapeu�c procedure.

✅✅ LIMITATIONS: 1. The follow-up makes this type of study design very costly. As you want the subjects to continue

the study for the follow-up period, you might need to give them financial incentives.

2. Time-consuming.

3. The possible loss to follow-up as a patient may drop out of the study, move to another residen-

tial area, or even die.

4. Not as powerful as randomized controlled trials (Figure 2). This is because in cohort studies you

do not control the exposure, while in the RCTs you randomly assign the predictor to the groups.

☑☑

COHORT STUDIES

Definition: A cohort in Roman times was a group of soldiers.

In medical context is a group of people with a shared characteristic.

A cohort study is when a group of people with a common exposure or risk, are followed (prospective) into the future to see whether they develop the target outcome or disease or not.

5. It very inefficient to use a cohort to study a rare outcome. Even for a relatively common disease

(like breast cancer for example) to appear it takes a very long time of follow-up (in this case you can use a retrospective cohort or a case-control study).

FOLLOW UP

6. Susceptible to selection bias as subjects may leave the study.

7. Surveillance bias.

8. Confounding bias.

GROUP OF INTEREST (SMOKERS)

COMPARE OUTCOMES

9. Zero-time bias.

FOLLOW UP

COMPARISON GROUP (NON-SMOKERS)

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

Study Designs

ACTIVITY

ANALYSIS: ✅✅ Incidence:

As we mentioned, while prevalence can be calculated from Cross-Sectional Studies, incidence rate can be calculated from cohort studies. Incidence is the number of new cases per population.

The incidence rate is the number of new cases of a disease in a specific population within a specific time, it can be calculated by the following formula:

Incidence Rate =

Total number of new cases of a diease in a specific timeIndcidence

x 100n

Total population at risk during the same time period

480

☑☑

ACTIVITY (2) FOR “CROSS SECTIONAL STUDIES”

Print the following study and ask your participants to recognize the study design Bobak M, Skodova Z, Marmot M. Beer, and obesity: a cross-sectional study. Eur J Clin Nutr. 2003 Oct;57(10):1250-3. PubMed PMID: 14506485.

ACTIVITY (3) FOR “PREVALENCE”

The total number of people with diabetes in England in 2011 was 2,455,937 while the total population was 44,653,400 so the prevalence of diabetes in England in 2011 was:

x 100 = 4.8%

10,000

ACTIVITIES (3),(4) FOR “COHORT S T U D I E S” ☑☑

This means that in that population, for every 1000 non-diabetic persons you would expect 24 to develop diabetes within 1 year. ✅✅ Risk and Risk ratio:

At the end of the cohort study, you want to know the «risk» of developing disease A if you have the risk factor B. Therefore, we start by filling out a 2 by 2 table describing the number of exposed and unexposed subjects who develop and do not develop the disease.

Then, risk can be calculated by the following formula:

Disease

Exposure

Total

Yes

No

Yes

d1

d0

d1+d0

No

h1

h0

h1+h0

Total

d1+h1

d0+h0

n=h1+h0 +d1+d0

d= diseased 1= exposed

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ACTIVITY (1) FOR CASE SERIES AND CASE REPORTS

Which type of study designs are used to study a rare condition? Answer: Case-series and case studies.

☑☑

For example, if a population of 10,000 nondiabetic people was followed for 2 years, and then 480 of that developed diabetes in that period, the incidence rate for that population would be:

Incidence Rate =

☑☑

h= health 0= unexposed

✅✅ You can divide your participants into two

or more groups, give them printed cohort studies, case reports, and case series, ask them to identify the study design and the reason behind their choice.

✅✅ You can explain the concept of cohort studies

by choosing a group of volunteers and then acting the study stages with them in front of the remaining participants (select them, assign them different exposures by giving them pieces of papers with the exposure written on them and then act the follow-up period.

In the end, you hand out pieces of paper with the condition or the disease written on it to some of the volunteers to explain the disease developing).

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

STUDY DESIGNS

**

Study Designs

CASE-CONTROL STUDIES

A case-control study is a retrospective study where you start with a diseased group of people (case group) and another healthy group (control group) and study their history looking for a certain risk factor.

Looking at (Figure 3) you can see that a case-control study goes on in the past.

When we say subjects at risk at the beginning of the study we mean the subjects who had the risk factor but didn’t have the disease at the start.

Risk ratio or relative risk (RR) compares the risk of developing disease «relatively» between the exposed group and the unexposed group.

Risk Ratio =

TAKE HISTORY

PATIENTS WITH CONDITION (CANCER)

DRAW CONCLUSIONS

TAKE HISTORY

COMPARE HISTORIES

COMPARISON GROUP (NON-PATIENTS)

factor and an outcome.

2. However, case-control studies are much cheaper and less time exhausting (just reveal hospital

records).

3. Case-control studies are also more useful in studying rare diseases (imagine a case-control

study and a cohort study investigating if there›s an association between male circumcision and carcinoma of the penis).

Cumulative Incidence (Unexposed Group)

So the risk of disease in exposed = risk of disease in unexposed, then the risk ratio will be 1 meaning that both groups had the same risk of developing the disease whether exposed to the risk factor of interest or not.

If the risk of the disease in exposed > risk of disease in unexposed, then the risk ratio will be >1, meaning that exposure to the risk factor of interest increases the risk of the disease.

If the risk of the disease in exposed < risk of disease in unexposed, then risk ratio will be <1, this means that the risk factor had a protective effect and decreased the risk of the disease.

Example: A cohort study was performed on people who had 2nd and 3rd degree burns to see if there’s an association between burns and skin infection, the results are shown in (Figure 7).

Burned group

Non-burn group

With skin infec�ons

45

20

No skin infec�ons

70

100

IMPORTANCE: 1. A case-control study is, like cohort studies, useful in measuring the association between a risk

Cumulative Incidence (Exposed Group)

Incidence of skin of infection in the burned group = 45/(45+70)=45/115=0.391=39.1% Risk ratio = (45/(45+70))/(20/(20+100))=0.391/0.167=2.34 This means that burned people have a 2.34 higher risk of developing skin infection within the follow-up period than non-burned people.

4. They are also very useful in generating hypotheses, which can be followed by a cohort for fur-

ther investigations.

5. Also, when there’s a long time lag between the risk exposure and the disease.

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STUDY DESIGNS

Study Designs

LIMITATIONS: 1. Weaker evidence than cohort studies (Figure 2).

Example: A case-control study was made to assess if there’s an association between eating processed red meat and having colorectal cancer. Two groups were included in the study, one group had colorectal cancer and the other group was healthy. Both groups were interviewed and asked about eating processed red meat in their diet. Results are summarized in the following table:

Cases

Controls

With diet depending on processed meat

110

75

Diet free from processed meat

90

125

2. It can only measure one outcome. This is because the selection of your cases depends on this

outcome (diseased vs not diseased) whereas in the cohort and cross-sectional studies you can measure multiple outcomes.

3. Like cohort studies, case-control studies lack control over risk assignment.

4. Do not give information about incidence or prevalence.

5. Might be susceptible to recall bias.

Example: Teo KK, Ounpuu S, Hawken S, Pandey MR, Valentin V, Hunt D, Diaz R, Rashed W, Freeman R, Jiang L, Zhang X, Yusuf S; INTERHEART Study Investigators. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study. Lancet. 2006 Aug 19;368(9536):647-58. PubMed PMID: 16920470.

ANALYSIS:

Odds of eating processed meat in the case group =110/90=1.2 Odds of eating processed meat in control group =75/125=0.6 OR =1.2/0.6=2 This means that patients with colorectal cancer are 2 times more likely to be eating processed meat in their diet compared to healthy individuals.

To measure the association between an exposure and an outcome in case-control studies, we use the odds ratio.

An “odd” is the probability of an exposure happening in one group to the probability of it not happening. (See Figure 6: Summarizing cohort and case-control studies results.)

Intervention

Outcome

Odds Ratio

A

B

C

D

=

AxD BxC

The odds ratio (OR) compares the odds of exposure in the case group and that of the control group.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

Study Designs

**

INTERVENTIONAL STUDIES (CLINICAL TRIALS)

An interventional or experimental study is when an intervention is applied to the subjects of the trial, and then an outcome or more is measured.

Non-blinded

IMPORTANCE: 1. Clinical trials (unlike observational studies) can demonstrate causality.

2. They are used exclusively in testing for prophylactic and therapeutic agents.

According to blinding

Only patients are blinded to the drug

Single blinded

3. Randomized clinical trials are very powerful evidence (Figure 2).

LIMITATIONS: 1. Very expensive as investigators have to pay for treatment, lab tests, or financial incentives.

Double blinded

Both patients and the investigators are blinded

2. May be unethical or inappropriate.

TYPES AND PHASES: Randomized

PRECLINICAL

PHASE 1

PHASE 2

PHASE 3

FDA review

PHASE 4

To confirm safety and effectiveness 20 - 80 participants • Evaluate safety • Determine safe dosage • Identify side effects

Drug approved for testing in humans

• Test effectiveness • Further evaluate safety

According to randomiza�on Non-randomized

1,000+ participants

100 - 300 participants • Confirm effectiveness • Monitor side effects • Compare to other drugs • Collect information

Drug submitted for FDA approval

• Provide additional information after approval including risk, benefit, and use.

single arm

A study including the experimental group only

According to control group FDA approval

controlled

29

More advatagous to avoid any bias and get more generalizable results

A study with a control group who will have a placebo (a pill that looks, smells, and tastes like the intervention drug but doesn’t contain an active material.)

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Study Designs

Study Designs

**

DIAGNOSTIC STUDIES

Diagnostic studies resemble the observational studies we discussed before, but instead of looking for an association between a risk factor and a disease, these studies – as the name suggests – focus on testing the usefulness of diagnostic, prognostic, and screening tests in medical practice.

To assess the usefulness of a medical test to physicians we have to consider the following variables: ✅✅ Accuracy: 1. Sensitivity 2. Specificity ✅✅ Reliability

+ -

TP FP

FN

Accuracy

Reliability

Does the test give the correct answer?

Does the test give the same answer whenever performed on the same patients (even if the answer is wrong)?

TN NOT RELIABLE NOT ACCURATE

NOT RELIABLE ACCURATE

RELIABLE NOT ACCURATE

RELIABLE ACCURATE

Disease status Test result

Diseased

Healthy

Posi�ve

True posi�ve (TP)

False-posi�ve (FP) (Type 1 error)

Nega�ve

False-nega�ve (FN)

True nega�ve (TN)

(Type 2 error)

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Study Designs

☑☑

ACTIVITY

SECONDARY RESEARCH STUDY DESIGNS

The huge amount of evidence published every day called for a way for busy clinicians to check the published literature on different topics, thus the need for a secondary research design.

Secondary research is the research that reviews, summarizes, and critically appraises already published research papers (Table 1: the difference between primary and secondary research).

This review process can be done to express an opinion or summarize the literature from one›s point of view on a specific topic (literature review) or done systematically according to the peer-reviewed protocol (systematic reviews). **

LITERATURE REVIEW

A literature review is a summary of the literature on a specific topic. Literature reviews do not follow any methodology thus are not reproducible and very prone to bias (you can see it at the bottom in Figure 2: Evidence pyramid). **

They are less prone to bias than literature reviews and are considered the most powerful evidence in the evidence hierarchy (Figure 2: Evidence pyramid).

A systematic review (paired with a meta-analysis) can answer a research question based on pooled data from published literature and thus used to write the practice guidelines.

READING A META-ANALYSIS: A meta-analysis is the statistical analysis of all published research data on a specific topic.

ACTIVITY (1) FOR “COHORT AND CASE-CONTROL STUDIES”

You can hand out a printed summary of cohort and case-control studies and ask the participant to calculate the odds ratio and risk ratio. ☑☑

ACTIVITY (2) FOR “CLINICAL TRIALS”

You can divide your participants into several groups, then hand out pieces of paper with multiple scenarios of research questions, and let them design a study for investigating this research question demonstrated on their teammates (the questions doesn’t have to be serious).

SYSTEMATIC REVIEWS AND META-ANALYSIS

Systematic reviews, on the other hand, rely on a peer-reviewed protocol, and are therefore reproducible.

☑☑

1

Defining the question and eligibility crtiteria

2

Searching for studies

3

Selecting the studies

4

Data extraction

5

Data analysis

6

Interpretation of the results

☑☑

ACTIVITY (3) FOR “DIAGNOSTIC TEST ACCURACY”

You can hand out printed studies describing the diagnostic accuracy of a test and ask the participants whether they should use this test in screening for example (when you want to detect all true positive cases).

The data of each study is represented with a circle or a square that has a size proportionate to the study weight.

Each circle has two arms representing a 95% confidence interval (see statistics).

The pooled results from all studies are represented by a diamond at the bottom of the plot.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

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Study Designs

☑☑

AN ALGORITHM FOR IDENTIFYING STUDY DESIGN Identify the question Prepare the protocol

START

Search for studies Assigned intervention?

No

Observational study

Yes Comparison group?

Experimental study

No

Descriptive study

Selcetion of potential studies

Yes Random allocation?

No

Non-randomized controlled trial

Extract data from selected studies

Analytical study

Yes

Quality assessment of studies

Direction of exposure

Randomized controlled trial

Case report/ series

Combine the data (synthesis or meta analysis) Discuss and conclude overall findings

Cohort study

EXPOSURE

OUTCOME

Case-control study

EXPOSURE

OUTCOME

Cross-sectional study

EXPOSURE AND OUTCOME AT THE SAME TIME

Systematic review This forest plot is from a meta-analysis assessing if there’s an association between mother›s passive smoking and the difference in baby›s birthweight.

You can see from the forest plot that the diamond is not set not overlapping the zero value, thus the study implies the adverse effects of passive smoking.

An iconic example of an important meta-analysis that saved many lives comes from Cochrane.

It’s from a study assessing the effectiveness of administering corticosteroids to mothers that are having premature babies in saving lives compared to a control group. The results were significant, and the study was very influential in the medical practice (because obstetricians at that time knew the effectiveness of this treatment ) that the forest plot from this study became the logo of the organization.

35

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

why learn statistics?

68.3%

95.4% 99.7% 1. All the results of clin numbers

2. To avoid the overesti

ical research are repost ed in

mation of the results au thors could be doing and ha ve a correct real interp retation of the results

Chapter 3

STATISTICS

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

Statistics

☑☑

ICH STATISTICS WH A DESCRIBE DAT Percentages Mean Median Mode tion Standard devia

BIOSTATISTICS:

The application of statistical methods and tests to topics and research related to biology and medicine. It includes the designing and development of the tests and the collection and analysis of the data from those tests.

STATISTICS WH IC TEST DIFFEREN H CES T

test and other p arametric tests Mann-Whitney and other non-parametr ic tests Chi-square test

Research

Interven�onal

STATISTICS WHICH ANALYZE RELATIONSHIPS

Secondary

Primary

Descrip�ve

Quan�ta�ve

Inferen�al

Qualita�ve

Quan�ta�ve

Qualita�ve

Figure 1: different kinds of research

☑☑

Risk ratio Odds ratio Risk reduction ed to Numbers need treat (NNT )

Correlation Regression

Observa�onal

Clinical Trials

ICH STATISTICS WH K COMPARE RIS

QUANTITATIVE/CONTINUOUS DATA:

STATISTICS WH IC ANALYZE SUR V H IVAL Su

STATISTIC WHICH T S E CONFIDE ST NCE

rvival analysis: Kaplan-Menier p lots Cox regression m odel

Confiden ce interv al P value

Data which would be presented numerically and consists of an infinite number of unique values.

EXAMPLE: weight (93.60 kg), height (176.59 cm), diastolic pressure (77.28 mm Hg), etc.

ICH STATISTICS WH ESCLINICAL INV D TIGATIONS AN SCREENING

ificity, and Sensitivity, spec es predictive valu ent and Level of agreem Kappa

39

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Statistics

ACTIVITY ☑☑ Write down the 7 terms listed above on a board and then hand out as many papers with statements on them as you want to everyone. Then ask them to discuss together which term best describes which statement and after they’re done ask them to individually write down one statement under its appropriate term.

Population People from Cairo

Sample White

women from Paris

Variable

Height

Students who Students

from Harvard

work with

dangerous

equipment in

Blood

glucose level

Harvard

Diabetic

People in the world

Amputees

from Brazil

Resting

metabolic rate

Parameter Probability Calories consumed daily by an obese person from Washington Resting metabolic rate of a top athlete from Jamaica Amount of times a 19-COVID patient washes their hands daily

Chance of a person living in

China to have 19-COVID

Chance of a

top athlete to have a heart attack

Chance of the Huntington’s allele to be

passed to an offspring

Ratio

Proportion Globulin 10ml conc. in of blood/All protein conc.

10ml of In blood Amount of depressed people compared to everyone from London No. of 19-COVID patients compared to everyone in Italy

QUALITATIVE/CATEGORICAL DATA:

Data in which you can make a distinction between the values and they can be grouped in a limited number of categories.

EXAMPLE: gender (M/F), age group (0-10/10-20/etc.), pregnancy (+/-), etc. ☑☑

DESCRIPTIVE STATISTICS:

Statistics which are concerned with data summarization and presentation of data gathered without making any conclusion or analysis of the data. ☑☑

INFERENTIAL STATISTICS:

Statistics allow us to look back on the data and make our conclusions and analyses of the data and what it means to the purpose of the study and the participants and whether the results obtained can be generalized over the entire population or not. ☑☑

STATISTICAL TERMS: ✔✔ Population: All possible members that you want to study. ✔✔ Sample: A subset of the population that you test on. ✔✔ Variable: Any characteristic that can be measured or counted. ✔✔ Parameter: The quantitative characteristic that you’re interested in measuring and testing. ✔✔ Probability: Measure of the likelihood of an event or occurrence. ✔✔ Ratio: Simply one number divided by another. ✔✔ Proportion: A ratio in which the numerator is a subset of the denominator.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Statistics

**

Statistics

☑☑

INTERQUARTILE RANGE:

ORIGINS OF THE BELL CURVE:

The range of values between the first quartile (Q1) and the third quartile (Q3).

The bell curve resulted from a simple bar chart of normally distributed data that was then simplified into the bell curve we all know.

Values must first be organized ascendingly.

Normally distributed data is data which features the highest amount of results at the mean and gradually lessens as you move towards both extremes.

Usually used when the middle value is described as median.

40

At the first value, we mark the beginning of Q1. After 25% of the values, we mark the end of Q1. After 50% of the values or 25% from the Q1, we mark off the median (Q2). After 75% of the values or 25% from the median, we mark Q3. After 100% of the values or 25% from Q3, we mark off Q4.

BELL CURVE

30 20 10 0

Thus, the IQR - which is the difference between Q3 and Q1 – represents 50% of the values collected. ☑☑

120

140

160

180

Figure: bell curve

200

CENTRAL TENDENCY: (DESCRIPTIVE-QUANTITATIVE) **

MEAN:

Sum of all measurements divided by the total number of measurements.

Q1

Q1 - 1.5 x IQR

Q2

Q3 + 1.5 x IQR

Median -3σ

-2σ

-1σ

43

-3σ

2σ

3σ

4σ

2.698σ

-2σ

-1σ

-2σ

0σ

24.65% 1σ

68.3%

15.73% -4σ

1σ 0.6745σ

-2.698σ -3σ

0σ

50%

24.65% -4σ

-0.6745σ

-4σ

-1σ

0σ

2σ

3σ

4σ

15.73% 1σ

2σ

3σ

4σ

When a graph is divided into quartiles, we can represent it as a Box Plot Graph by simply drawing a box with the width of the IQR and then extending 2 lines from both the Q1 and Q3 ends.

The bottom graph represents the standard deviation markings and how the graph would look if it were divided based on the standard deviation markings.

Thus comparatively, the IQR (50%) will always be slightly smaller than the area of the first SD (68%).

**

MEDIAN:

The middle value when values are arranged ascendingly. **

MODE:

The most frequent value of the group values. ☑☑

MEASURES OF SPREAD: (DESCRIPTIVE-QUANTITATIVE) **

1. RANGE:

The difference between the maximum value and the minimum value.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Statistics

ACTIVITY **

Discuss and solve the following example with the students

STANDARD DEVIATION:

Measure of the degree of spread of each value from the mean value. (The percentage of data centered around the mean value.)

Mean = 157.48 + 165.099 + 172.72 + 152.4 + 167.64 / 5 = 163.0678 cm

Used with normally distributed data

Corin: 163.0678 – 157.480 = 5.5878

Name

Jen: 163.0678 – 165.099 = -2.0312

Height/cm

Corin

Raffy: 163.0678 – 172.720 = -9.6522

157.480

Jen

Jessie: 163.0678 – 152.400 = 10.6678

172.720

Jessie

σ2 = 5.58782 + (-2.0312)2 + (-9.6522)2 + 10.66782 + (-4.5722)2 / 5 σ2=52.644242

[Check the activity in the next page]

165.099

Raffy

Kat: 163.0678 – 167.640 = -4.5722

1σ=68% 2σ=95% 3σ=99%

152.400

Kat

**

167.640

VARIANCE:

The square of the Standard Deviation.

σ = 7.2556352

Thus, we can say that 68% of the values lie within 163.0678±7.2556352, and 95% of the values lie within 163.0678±(2x7.2556352), and 99% of the values lie within 163.0678±(3x7.2556352).

☑☑

**

Kat 167.64 cm Corin 157.48 cm

CONFIDENCE INTERVAL:

A type of estimate that predicts a range of plausible values for an unknown parameter as well as a confidence level that the true parameter is in the proposed range. In simpler words, it means the interval x1:x2 where you’re y% confident that the true value lies within.

Jen 165.099 cm

Jessie 152.4 cm

CONFIDENCE TESTS (INFERENTIAL-QUANTITATIVE):

Raffy 172.72 cm

-4σ

-3σ

-2σ

-1σ

μ

1σ

2σ

3σ

4σ

-192 cm

-184.75 cm

-177.50 cm

-170.25 cm

163cm

170.25 cm

177.50 cm

184.75 cm

192 cm

True value is the unknown parameter that we would obtain if we tested the entire population rather than a sample, which is frankly impossible.

POPULATION

sample

TRUE VALUE

obtained value

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Statistics

☑☑

Statistics

DIAGNOSTIC TEST ACCURACY: **

EXAMPLE: In a sample of 50 patients, we test a new type of sleeping pills to treat insomnia. The number of sleeping hours before and after taking the pills was recorded over a period of one week.

SCREENING TEST:

A highly sensitive test used to screen a wide population to find all possible infected people. **

DIAGNOSTIC TEST:

A highly specific test used to eliminate the false positive data from the pool of data obtained from the screening test. **

SENSITIVITY:

Used to describe how good a test is at detecting all infected people without missing any and usually results in detecting some uninfected people as infected, thus it might have false-positive results but never any false-negative results. (Always trust the negative result.) **

SPECIFICITY:

Used to describe how good a test is at not detecting any uninfected people and usually results in detecting some infected people as uninfected, thus it might have false-negative results but never any false-positive results. (Always trust the positive result.)

Classification according to test

A: True Negative B: False Positive

(B) (A)

C: True Positive

(C) (D)

D: False Negative

That means that we›re 95% confident that if we tested all insomnia patients with these pills, the number of sleeping hours will increase by several hours from 1.5 hours to 2.5 hours.

If the results lie outside the 95% CI, then it will lie in the other 5%, so it won’t be significant as it is in the p-value area of the results happening due to chance as we’ll discuss now. **

P-VALUE:

The probability of obtaining results supporting the null hypothesis. (The probability of the results happening due to chance only.)

The null hypothesis is the opposite of your hypothesis. So, for example, if you’re testing if a certain antidepressant would help depression patients, the null hypothesis would be that it doesn’t help depression patients.

The smaller the p-value is, the less likely the null hypothesis is.

The p-value is usually provided with most statistical software. ✔✔ If the p-value is ≤0.05 (5%) then the results are significant, and we reject the null hypothesis as

the probability of the results occurring if the null hypothesis is true is very small.

✔✔ If the p-value is >0.05 (5%) then the results aren’t significant enough to reject the null hypothe-

sis. This does not mean that the null hypothesis is true, it just means that we don’t have enough evidence to reject it.

If the test is sensitive, move y-axis line to the left If the test is specific, move y-axis line to the right

**

The average/mean difference of sleeping hours was +2 hours, thus when calculated, we get 95% confidence interval (+1.5:+2.5).

Overall, the CI is a better indicator of statistical and clinical significance.

GOLD STANDARD:

A test that has 100% accuracy and gives neither false-positive results nor false-negative results.

Such tests are very few in medicine.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

Critical Appraisal

“A 21st-century clinician who cannot critically read a study is as unprepared as one who cannot take blood pressure or examine the cardiovascular system.» (BMJ 2008:337:704-705). ☑☑

ENTRANCE:

When you search for any medical issue, you will find a lot of papers, maybe thousands of them, using some filters in your search engine may reduce the number, but of course, you need more than filters to appraise the data collected, you need an efficient tool to focus on the highest quality, relevant and accurate studies. ☑☑

DEFINITION:

Critical appraisal is the process of carefully and systematically assessing the outcome of scientific research (evidence) to judge its trustworthiness, value, and relevance in a particular context. (1) ☑☑

STEPS OF CRITICAL APPRAISAL: Validity

1. Assess relevance.

2. Assess the initial validity 3. Assess the study design 4. Assess the statistical appraisal.

** STEP 1: ASSESS RELEVANCE (External validity) Through this step, we carefully read the abstract of the study to be able to answer the following questions:

Value and relevance

Trusworthiness of results

✅✅ Does this information directly impact my case? ✅✅ Do these cases look like mine? ✅✅ Is this intervention available in my practice?

After answering these key questions, you will have the answer to the most important question in this step: ✅✅ Is it worth reviewing in-depth?

49

Chapter 4

CRitical Appraisal

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

Critical Appraisal

**

ACTIVITY

STEP 2: ASSESS THE INITIAL VALIDITY

Now, that you’re sure that the study is relevant, those are exactly the type of patients that you take care of, and that’s what you want to read, the next step is to assess the initial validity of the study, by trying to answer the following questions:

☑☑

✅✅ Where is the article published?

You have to remind your trainees of the EBM steps and ask them to find some reasons why we need an appraisal tool.

A graph presenting the type of journals:

You may ask them to search about a medical issue using “PubMed” then discuss with them how to include or exclude studies: critical appraisal intro.

1. Peer-reviewed journals: parent journals, etc.

2. Unsolicited: predator journals

Impact factor: This is a measure of the frequency of which the average article in a journal has been cited in a particular year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited.

Who sponsored the study? As said before: «Science is not always the prime motive», so we need to check the author›s financial disclosures, commercial organization, and degree of involvement in the design and results. **

STEP 3: ASSESS STUDY DESIGN

✅✅ Was the study design appropriate for the research question?

Studies that answer questions about effectiveness have a well-established hierarchy of study designs based on the degree to which the design protects against bias.

Systematic reviews Critically-appraised topics (evidence systheses and guidelines)

Critically appraised individual articles (article synopses)

Randomized controlled trials (RCTs)

Background information / expert opinion

UNFILTERED INFORMATION

Cohort studies

Case-controlled studies case series / reports

51

FILTERED INFORMATION

This figure illustrates the hierarchy of evidence, it’s called the EBM Pyramid: showing the quality of evidence in an ascending order. There are some ready checklists for each study design but we will try here to discuss some key points we find to be the most important and basic to appraise each design.

ACTIVITY (1) FOR CRITICAL APPRAISAL

☑☑

ACTIVITY (2) FOR “STEP 1: ASSESS RELEVANCE”

To answer these questions, you may ask your trainees to identify the research question by the PICO method for an abstract you have prepared. ☑☑

ACTIVITY (3) FOR “STEP 2: ASSESS THE INITIAL VALIDITY”

To answer these questions, you may print some papers for the trainees and ask them to search for the impact factor of the journal, and to compare between two or more IFs, then ask them to discuss the financial disclosure to find any conflict of interest.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Critical Appraisal

đ&#x;&#x201D;´đ&#x;&#x201D;´ EXPERIMENTAL STUDIES: Randomized control trials: First of all, we have to check the internal validity of the RCTs, â&#x153;&#x2026;â&#x153;&#x2026; Blinding: We need to look to the degree of blinding allocated to check any investigator or

subject bias.

â&#x153;&#x2026;â&#x153;&#x2026; Randomization: In an RCT, the random allocation of participants should ensure that treatment

groups are equivalent in terms of both known and unknown confounding factors, any differences in outcomes between groups can therefore be ascribed to the effect of treatment.

â&#x153;&#x2026;â&#x153;&#x2026; Intervention: To ensure that the two groups are treated equally and the RCT compares apples

to apples in doses, the spectrum of activity and the duration.

đ&#x;&#x201D;´đ&#x;&#x201D;´ SYSTEMATIC REVIEWS AND META-ANALYSIS: A meticulous, standardized protocol is used in a systematic review to identify, critically appraise, and synthesize all the relevant studies on a particular topic. Although planning to undertake a systematic review or a meta-analysis prospectively is possible, the majority of these types of articles are retrospective and the risk of bias exists, which arises from the selection of studies and the quality of these primary sources. Publication bias, which results from the selective publication of studies with positive findings, is of particular concern, as it distorts overall perceptions of the findings on a particular topic. **

STEP 4: ASSESS THE STATISTICAL ANALYSIS

Critical Appraisal

đ&#x;&#x201D;´đ&#x;&#x201D;´ DESCRIPTIVE STUDIES: As discussed before in the study design section, we know that descriptive studies are not studies, they always describe an event, such as unexpected event during treatment, or rare disease or feature. Therefore, they allow for hypothesis generation. đ&#x;&#x201D;´đ&#x;&#x201D;´ CASE-CONTROL STUDIES: Retrospective and measure the association between an exposure and a disease by the odds ratio.

(Discussed before) The major methodological difficulties with case-control studies are the selection of appropriate control individuals and the possibility of â&#x20AC;&#x153;recall biasâ&#x20AC;? (a patientâ&#x20AC;şs subjective interpretation of what caused their condition can alter their recall of certain events or experiences).

Controls should be drawn from the same population as the cases, and the only difference between controls and cases should be that the controls have not developed the condition of interest. Although objective measures of possible causative factors are preferable, case-control studies often rely on participantsâ&#x20AC;ş recall, and patients might be more likely to remember certain events or experiences than controls. đ&#x;&#x201D;´đ&#x;&#x201D;´ COHORT STUDIES: Prospective in nature, measure the association of the exposure to the disease by the relative risk ratio. The major methodological concern with cohort studies is their high potential for selection bias and confounding factors. These problems are particularly relevant when cohort studies (or non-RCTs) are used to evaluate therapeutic interventions. In this situation, the treatment that someone receives is determined by the patientâ&#x20AC;şs or clinicianâ&#x20AC;şs preferences, referral patterns, current treatment paradigms or local policy.

Assessing the appropriateness of statistical analyses can be difficult for any statisticians. However, we will try here to mention some checkpoints that we find important to appraise a statistical analysis

I USED TO THINK CORRELATION IMPLIED CAUSATION.

53

THEN I TOOK A STATISTICS CLASS, NOW I DONâ&#x20AC;&#x2122;T.

SOUNDS LIKE THE CLASS HELPED. WELL, MAYBE.

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Scientific Writing

☑☑

INTRODUCTION

The most important step to be an evidence-based doctor is to be updated on recent research evidence and to be able to criticize it and apply its results. Also, you need to share your experience through publishing research papers. So, in this chapter we are discussing the structure of the scientific research paper, what each section discusses, and steps to get better scientific writing. ☑☑

STRUCTURE OF THE RESEARCH PAPER

This figure illustrates briefly the structure of the research paper.

Title, Author, Abstract, Keywords

Introduction

Methods

Results

Discussion/ Conclusion

References

55

Descriptive information that lets readers search for an articles.

What is the context for this project?

How does it fit in with other ressearch on the topic?

What is the research question?

What did the author(s) do to answer the research question?

What was the answer to the question?

This is often shown in tables and figures.

What is the significance of this project?

How does it fit with what else is known about the topic

Materials the author(s) cited when writing this paper

WH

Y?

HOW

?

WH SO

AT?

Chapter 5

WH

Scientific writing

AT?

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Scientific Writing

**

Scientific Writing

**

MANUSCRIPT TEXT (IMRAD):

I. INTRODUCTION: Why did you do the study? Setting the scene or laying the foundation or background for the paper.

R. RESULTS: What did you find?

D. DISCUSSION: What do these results mean? Itâ&#x20AC;&#x2122;s the place for interpreting the results.

Paragraph 1: What we know

of knowledge) to be solved.

Paragraph 2: What we donâ&#x20AC;&#x2122;t know

â&#x153;&#x2026;â&#x153;&#x2026; Why we did this study: Describe where your reParagraph 3: Why we did this study?

was done.

â&#x153;&#x2026;â&#x153;&#x2026; Inclusion and exclusion criteria.

â&#x153;&#x2026;â&#x153;&#x2026; Conflicts of Interest [if needed]: List and explain any conflicts of interest.

**

ABSTRACT:

â&#x153;&#x2026;â&#x153;&#x2026; About 200-400 words (according to journal/conference instructions). â&#x153;&#x2026;â&#x153;&#x2026; It helps readers have a general outline of your paper and determine whether it is within their

Paragraph 1: Describe study sample. who did you study?

â&#x153;&#x2026;â&#x153;&#x2026; Where and when the study was performed. â&#x153;&#x2026;â&#x153;&#x2026; Population: patients, etc. (if applicable).

â&#x153;&#x2026;â&#x153;&#x2026; Financial & Equipment Support [if needed]: Specific information about organizations, agen-

â&#x153;&#x2026;â&#x153;&#x2026; May be structured as: introduction, methods, results, and conclusion. Or as one paragraph.

In this section we describe: â&#x153;&#x2026;â&#x153;&#x2026; The specific study design: How the experiment

â&#x153;&#x2026;â&#x153;&#x2026; Keywords: According to the journal

â&#x153;&#x2026;â&#x153;&#x2026; Summary of the research paper.

search fits into the current science.

đ&#x;&#x201D;´đ&#x;&#x201D;´ METHODS:

â&#x153;&#x2026;â&#x153;&#x2026; Corresponding Author: Full name and affiliation of the primary contact author for persons who

cies, or companies that supported the research.

rize the current understanding of the problem.

â&#x153;&#x2026;â&#x153;&#x2026; What we do not know: Describe the problem (gap

reviewed the work and/or aided in study design or data analysis (International Committee of Medical Editors, 1997). Check the instructions to authors for the target journal for specifics about authorship. have questions about the research.

đ&#x;&#x201D;´đ&#x;&#x201D;´ INTRODUCTION: â&#x153;&#x2026;â&#x153;&#x2026; What we know: use primary literature and summa-

â&#x153;&#x2026;â&#x153;&#x2026; Title: Tells the reader what to expect in the paper. â&#x153;&#x2026;â&#x153;&#x2026; Author(s): Most papers are written by one or two primary authors. The remaining authors have

M. METHODS: How did you do the study?

In this section, we discuss these three issues.

THE TITLE PAGE:

scope or not.

â&#x153;&#x2026;â&#x153;&#x2026; For indexing purposes in search databases. â&#x153;&#x2026;â&#x153;&#x2026; Conference presentations.

Paragraph 2: Univariate analyses How many participants had what?

Tip: Write the abstract last after the main text to make sure that the important information is included in the summary.

â&#x153;&#x2026;â&#x153;&#x2026; Sampling strategy. â&#x153;&#x2026;â&#x153;&#x2026; Intervention/Condition being observed and how

it applies.

â&#x153;&#x2026;â&#x153;&#x2026; Why experimental procedures were chosen. â&#x153;&#x2026;â&#x153;&#x2026; Outcome measurement, data collection instru-

ments, and procedures.

â&#x153;&#x2026;â&#x153;&#x2026; Methods of analysis and how results were analyz-

Paragraph 3: Bivariate analyses, Whatâ&#x20AC;&#x2122;s the relation between the outcome and explanatory variables?

Paragraph 4: Multivariate analyses Whatâ&#x20AC;&#x2122;s the result when the confounders and the eďŹ&#x20AC;ect modiďŹ ers have been taken into account?

ed.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Scientific Writing

đ&#x;&#x201D;´đ&#x;&#x201D;´ APPENDICES: â&#x153;&#x2026;â&#x153;&#x2026; Acknowledgment: Names people who contributed to the work but did not contribute suffi-

ciently to earn authorship. You must have permission from any individuals mentioned in the acknowledgment sections.

â&#x153;&#x2026;â&#x153;&#x2026; Funding Source â&#x153;&#x2026;â&#x153;&#x2026; Conflict of Interest â&#x153;&#x2026;â&#x153;&#x2026; Figueresâ&#x20AC;&#x2122;s Legend

đ&#x;&#x201D;´đ&#x;&#x201D;´ REFERENCES: Complete citations for any articles or other materials referenced in the text of the article. â&#x2DC;&#x2018;â&#x2DC;&#x2018;

RULES FOR GOOD SCIENTIFIC WRITING **

Scientific Writing

đ&#x;&#x201D;´đ&#x;&#x201D;´ RESULTS: In this section we state what we found: â&#x153;&#x2026;â&#x153;&#x2026; Present key findings concerning the central research question. â&#x153;&#x2026;â&#x153;&#x2026; Secondary findings: secondary outcomes, subgroup analyses, etc. â&#x153;&#x2026;â&#x153;&#x2026; Figures, charts, and captured images.

đ&#x;&#x201D;´đ&#x;&#x201D;´ DISCUSSION: The place where we interpret the results and main findings of the study. â&#x153;&#x2026;â&#x153;&#x2026; Are results statistically significant? â&#x153;&#x2026;â&#x153;&#x2026; Are results clinically significant? â&#x153;&#x2026;â&#x153;&#x2026; Give possible justifications: why drug X was

better than drug Y?

INTRODUCTION:

â&#x153;&#x2026;â&#x153;&#x2026; Imagine that you are reading a scientific paper and you reached this sentence:

Discuss the main results concerning previous research:

â&#x153;&#x2026;â&#x153;&#x2026; â&#x20AC;&#x153;These findings imply that the rates of ascorbate radical production and its recycling via dehy-

â&#x153;&#x2026;â&#x153;&#x2026; What did previous studies conclude about

droascorbate reductase to replenish the ascorbate pool are equivalent at the lower irradiance, but not equivalent at higher irradiance with the rate of an ascorbate radical production exceeding its recycling back to ascorbateâ&#x20AC;?.

â&#x153;&#x2026;â&#x153;&#x2026; This sentence is hard to understand, and you got confused while reading it. So, you must re-

peat it more than once to get it well. And that wastes your time and is against the purpose of research.

â&#x153;&#x2026;â&#x153;&#x2026; The purpose of the research paper is to: â&#x153;&#x201D;â&#x153;&#x201D; Share knowledge gained with other researchers. â&#x153;&#x201D;â&#x153;&#x201D; Show how your study fits into the current science. â&#x153;&#x201D;â&#x153;&#x201D; Inform the public about the important scientific activities. â&#x153;&#x2026;â&#x153;&#x2026; And the previous sentence makes it hard to achieve these objectives. Therefore, through scien-

tific writing you must make your research easy to read and understand.

59

Paragraph 1: What did this study show? address the aims stated in the introduction

this topic?

Paragraph 2: Strebghes and weaknesses of methods

Paragraph 3: Discuss how the results support the current literature or refute current knowledge

â&#x153;&#x2026;â&#x153;&#x2026; Is your study under previous studies? â&#x153;&#x2026;â&#x153;&#x2026; If not, justify this contradiction.

Strengths and limitations of the study: â&#x153;&#x2026;â&#x153;&#x2026; Study strength points.

Paragraph 4: Future directions â&#x20AC;&#x153;So what?â&#x20AC;? and â&#x20AC;&#x153;where next?â&#x20AC;? impact on current thinking or practice

â&#x153;&#x2026;â&#x153;&#x2026; Study limitations.

Policy and practice implications of the results: â&#x153;&#x2026;â&#x153;&#x2026; Generalizability. â&#x153;&#x2026;â&#x153;&#x2026; Implications for clinical practice. â&#x153;&#x2026;â&#x153;&#x2026; Implications for future researchers. â&#x153;&#x2026;â&#x153;&#x2026; Conclusion.

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EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT

EVIDENCE-BASED MEDICINE MANUAL IFMSA-EGYPT IFMSA-EGYPT EVIDENCE-BASED MEDICINE MANUAL

Scientific Writing

**

IMPORTANT FACTORS FOR RESEARCH WRITING QUALITY:

đ&#x;&#x201D;´đ&#x;&#x201D;´ COHERENCE: â&#x153;&#x2026;â&#x153;&#x2026; Include all necessary information in each section. â&#x153;&#x2026;â&#x153;&#x2026; Donâ&#x20AC;&#x2122;t repeat information unless necessary.

đ&#x;&#x201D;´đ&#x;&#x201D;´ ORGANIZATION: â&#x153;&#x2026;â&#x153;&#x2026; Follow IMRaD (or journal-specific) structure. â&#x153;&#x2026;â&#x153;&#x2026; Put the right parts in the right places.

đ&#x;&#x201D;´đ&#x;&#x201D;´ RELEVANCE:

Scientific Writing

Example: Dysregulation of physiologic microRNA, miR, activity has been shown to play an important role in tumor initiation and progression, including gliomagenesis. Therefore, molecular species that can regulate miR activity on their target RNAs without affecting the expression of relevant mature miRs may play equally relevant roles in cancer.

After revision: Changes in microRNA expression play a role in cancer, including glioma. Therefore, events that disrupt microRNAs from binding to their target RNAs may also promote cancer. â&#x153;&#x2026;â&#x153;&#x2026; Put new information last: Most readers will find your writing clearer if you consistently begin

sentences with familiar (old) information and conclude sentences with unfamiliar (new) information.

â&#x153;&#x2026;â&#x153;&#x2026; Choose simple words: â&#x153;&#x201D;â&#x153;&#x201D; Methodology vs. method

â&#x153;&#x2026;â&#x153;&#x2026; Conform to length guidelines and keep the paper focused.

â&#x153;&#x201D;â&#x153;&#x201D; Utilize vs. use

â&#x153;&#x2026;â&#x153;&#x2026; Choose a limited amount of data to present in each section.

â&#x153;&#x201D;â&#x153;&#x201D; To vs. to

đ&#x;&#x201D;´đ&#x;&#x201D;´ CLARITY: â&#x153;&#x2026;â&#x153;&#x2026; Should be easy to read and understand. â&#x153;&#x2026;â&#x153;&#x2026; Use proper grammar, phrasing, and style.

**

TIPS FOR SCIENTIFIC WRITING:

â&#x153;&#x2026;â&#x153;&#x2026; Cut unnecessary, vague words and phrases (physiologic-molecular species), get rid of the clut-

ter.

â&#x153;&#x2026;â&#x153;&#x2026; Use of the active voice rather than the passive voice (such as: has been shown). â&#x153;&#x2026;â&#x153;&#x2026; Talk about actions using strong verbs. â&#x153;&#x2026;â&#x153;&#x2026; Avoid using unnecessary jargon (Gliomagenesis) and acronyms (miR) unless they are standard

terms.

â&#x153;&#x2026;â&#x153;&#x2026; Avoid turning verbs into nouns (dysregulation-progression-expression) or burying the main

verb. Make sure the verb is near the subject. (The subject â&#x20AC;&#x153;molecular speciesâ&#x20AC;? its verb is â&#x20AC;&#x153;may playâ&#x20AC;?.)

â&#x153;&#x2026;â&#x153;&#x2026; Use common, everyday words rather than complex words. â&#x153;&#x2026;â&#x153;&#x2026; Avoid long phrases.

Example: This study was performed to determineâ&#x20AC;Ś Revision: This study determinesâ&#x20AC;Ś â&#x153;&#x2026;â&#x153;&#x2026; Create a flow between sentences (make sure that the sentences match). â&#x153;&#x2026;â&#x153;&#x2026; Avoid repetition unless itâ&#x20AC;&#x2122;s needed.

**

4. POINT OF CONFUSION:

â&#x153;&#x2026;â&#x153;&#x2026; â&#x20AC;˘ The attendees may be confused between scientific writing and writing for literary works

and presenting your writing skills, such as in English language exams.

â&#x153;&#x2026;â&#x153;&#x2026; â&#x20AC;˘ To resolve this confusion, scientific writing aims to make the research paper easy to under-

stand for both native and non-native speaker and we use the simplest language.

â&#x153;&#x2026;â&#x153;&#x2026; â&#x20AC;˘ But when learning English, we use complex and non-familiar adjectives and phrases. As it

aims to measure our progress and knowledge of English as a language. It relies on finding the â&#x20AC;&#x153;structural complexesâ&#x20AC;? in your writing. While in scientific writing we use simple words.

â&#x153;&#x2026;â&#x153;&#x2026; â&#x20AC;˘ Donâ&#x20AC;&#x2122;t forget that proper grammar, spelling, and phrasing is necessary for scientific writing.

61

60

EBM MANUAL TEAM

ACTIVITY ACTIVITY (1) FOR ABSTRACT WRITING: You can print a paper abstract, divide attendees to 4 groups and ask each group to illustrate part of the abstract creatively.

ACTIVITY (2) FOR PAPER SECTIONS: You can divide attendees into small working groups and give them small pieces of papers containing specific information and ask them to put it in the correct section. Example: a paper with “study designs” written on it and they choose to put it in the methods section.

ACTIVITY (3) FOR SCIENTIFIC WRITING: You can show a bad example of scientific Mohammed Sadeq

Ahmed Hassan Sherif

MMSA-MUST Graphic Designer

MMSA-MUST Coordinator

writing and tell the attendees that it’s a good one, then ask them to share with you mistakes they see in it and take points. Then you can explain the exercise and that in fact it’s not a good one, adding any points they may have missed.

ACTIVITY (4) FOR TIPS FOR SCIENTIFIC WRITING: Provide the attendees with some examples that need to be reviewed and ask them to make the best changes to get better scientific writing.

ACTIVITY (4) FOR TIPS FOR POINT OF CONFUSION: You can ask the attendees to find out the point of similarity and differences between the two ways to make it clearer.

Ahmed Magay

Ahmed Khaled Awad

Abdelrahman Sidi

Omar Ahmed

Zeyad Hassan Hamed

Reem Ghorab

AMSA-Azhar Cairo

ASSA-Alexandria

AUSSS-AinShams

ASSA-Assiut

MSSA- Mansoura

MMSA-MUST