Walter Sisulu University Research Methods Workshop

Robert J Wilkinson Director, CIDRI-Africa

0900 19th August 2017, Mthatha

    Life expectancy globally, and in South Africa

www.healthdata.org/south-africa

    Trends of ill-health in South Africa

www.healthdata.org/south-africa

    IDM mission

• To be an African centre of excellence in which world class scientists using state-of-the-art facilities work together

• To combat the life-threatening infectious diseases of HIV/AIDS and tuberculosis

• To address regionally prevalent cancers and genetic diseases

    Research Methods workshop

Workshop orientation and overview

    Lecture plan

Saturday: The need for research in Africa Types of study How to structure a protocol Statistical considerations How to present data Experiences of up and coming researchers at WSU Sunday: Grant writing Specific opportunities within NIH program Funding opportunities in South Africa

    Research proposal development groups

Saturday and Sunday sessions followed by Friday presentation

Peer-driven, Faculty-facilitated

The chair will ensure fair time-keeping

Sunday: • Definition of research question

• Design and execution of study

Saturday: • Analysis

• Reporting and presentation

    Sunday oral presentations

•  A guide to stimulate conversation •  Concise is nice •  5 slides maximum: Large font •  Slide 1

–  Name and Present postion –  Background and Rationale

•  Slide 2 –  Objective(s) –  Abstract (very brief)

•  Slide 3 –  Schema

•  Slide 4 –  Study size and expected rate of accrual –  Expected challenges

    Housekeeping and thanks

Pamela Mda

Zukiswa Zingela,

Profs. Cishe, and Mahlomaholo

Kathryn Wood

Yolande XR Harley

Alan Sher

Bruno Andrade

    Hypothesis

•  “A supposition or proposed explanation made on the basis of limited evidence as a starting point for further investigation.”

•  A hypothesis is a statement of belief. The goal of your study is to discriminate between well-defined hypotheses.

    The research question

•  What is the uncertainty the investigator wishes to resolve? – Should post-menopausal women take

hormone-replacement therapy (HRT)? •  Not very specific question

– Does HRT reduce risk of cardiovascular disease in post-menopausal women?

    Study design

Start by considering the ideal study design,

without constraints of practicality or ethics.

This is a reference point from which to

consider what can be done within the actual

limitations.

    Types of scientific studies

•  Observational – Cohort: group followed over time – Cross-sectional: group examined at one point

in time – Case-control: two groups selected based on

absence or presence of outcome Many observational studies suggested HRT reduced risk of CVD in post-menopausal women.

    Why do observational studies?

•  Describe the real world

•  Ethical problems may prevent randomization

•  Investigator may lack authority or power to impose randomization or to control assignment of interventions

•  Impracticalities (e.g., cost, time, rare diseases)

•  Generate hypotheses

    Types of scientific studies

•  Clinical trial –  Randomized trial: two or more groups assigned

interventions by randomization

Why clinical trials? –  Only properly designed and executed experiments

can reliably demonstrate causation.

–  An observational study is often useful for identifying

possible causes of effects, but it cannot reliably

establish causation

   The essential difference between an experiment and an observational study

•  Observational studies suggested protection with HRT

•  Randomized controlled trials proved that HRT: –  Increased risk of heart attack –  Increased risk of stroke –  Increased risk of blood clots

    Clinical Trial Definition

•  A clinical trial requires the formal structure of an experiment, particularly control over intervention assignments by the investigator

•  A clinical trial is a experimental study in human volunteers, to answer specific health questions.

•  An essential characteristic of a clinical trial is that one uses results from a limited sample to make inferences about how interventions should be applied to a larger population (generalizability).

    Inherent tension in research

Pressure to •  Move quickly on findings

•  Be cutting edge

BUT must •  Be cautious and careful that results are real

•  Generate relevant results that generalize to the

correct population

    Equipoise

•  Uncertainty as to whether a new intervention is effective; the rationale for investigating a new intervention.

•  “Under the principle of equipoise, a patient should be enrolled in a randomized controlled trial only if there is substantial uncertainty (an expectation for equal likelihood) about which intervention will benefit the patient most.”

    Clinical trialist’s responsibilities

•  Possess altruism

•  Focus on objectivity; eliminate conflicts of interest

•  Adhere to ethical requirements

•  Respect the integrity of trial design/conduct

•  Comply with regulations (institutional and external)

•  Demonstrate resource/financial stewardship

   What does statistics bring to the process?

•  This should become evident through the process of

developing your protocol during this workshop.

•  Statistics helps with understanding and interpreting the

variability (inherent randomness and hidden variables).

•  If outcomes are deterministic then statistics do not

help!

•  Statistical models provide a basis for interpreting

variability.

   Population and Sample Groups

Target Population

Accessible Population

Study Sample

Intervention Group

Comparison Group

Ideally, the study sample represents the target population

    Developing a Protocol

•  Overall Purpose – Decide what question you want to

answer (or address) •  Scientific relevance of your experiment (“Why do we

care?”) •  What will happen if results are positive? Negative?

– Then develop Objective(s) • Experimental Hypothesis(es) –

testable, ethical, important. • Statistical Hypothesis(es)