Participant Guide Clinical Research Methodology

In Collaboration with the Egyptian Knowledge Bank

Nature Research Academies – Author Academy

Workshop Overview

___________________________________________________________________________________ The Nature Research Academies virtual workshops are designed to offer accessible training for busy journal editors. Through a combination of interactive group webinars and selfstudy exercises led by a Nature Research trainer, the workshop will help you to succeed in today’s competitive academic landscape. The goal of clinical research is to improve patient care and management; however, this can only be done if you have a robust and rigorous clinical study design. These webinars provide practical insights and strategies to help you achieve this goal. Participants who complete the workshop will be awarded a Certificate of Completion.

Objectives for this virtual workshop: 

Formulate a concise and impactful research question



Choose the best study design according to your study aim

Preparation for the workshop To prepare for the virtual workshop, please read through the key points of the workshop along with the activities, which should take you less than an hour. These exercises have been designed to help you to get the most out of the workshop. By reviewing them ahead of time, the trainer can focus on teaching and leading the activities more effectively during the sessions. We encourage you to try to answer the activities before the webinar, and then you can revise your answers during the webinar if necessary. You will also need to have access to this Participant Guide during the webinars. The Nature Research Academies team recommends that you either print or display it on a separate device to the one you are using to access the webinars.

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Agenda

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Webinar 1 – Planning Before You Begin Identifying an important research question This section discusses how to define a research question that will address an

Session 1

important problem in the field, and then how to decide the best aims to address this question.

Deciding the appropriate outcomes Session 2

This section reviews the variety of outcomes that can be evaluated and how to choose which ones are most appropriate based on the aims that have been decided.

10 minutes

Break

15 minutes

Q&A Choosing the best study design This section discusses different study designs along with their level of evidence,

Session 3

strengths & weakness, as well as associated biases that need to be taken into consideration during planning.

15 minutes

3

Final Q&A

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Key Points from this Workshop

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Webinar 1 – Planning Before You Begin Defining your research question Formulate your research question using: ●

●

the P–I–C–O approach, identifying: o

the Population studied

o

the Intervention of interest

o

the Comparison

o

the Outcome(s) measured

The F–I–N–E–R criteria; i.e., your study should be: o

Feasible: Do you have the expertise, resources and budget to complete your study on time?

o

Interesting: Does research question address an important topic in your field?

o

Novel: Does the study generate novel information about this topic?

o

Ethical: Are you respecting international guidelines related to human research? Did you obtain approval by a research ethics committee?

o

Relevant: What is the clinical relevance of your study?

Measurements The most common epidemiological measures are: ●

Frequency measures: o

The prevalence is a frequency measure of the existing cases of a disease over a given time period

o

The incidence is a frequency measure of the number of new cases of a disease over a given time period

●

Mortality measures: o

The mortality rate reflects the frequency of deaths in a population for a given time period

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o

The case-fatality risk reflects the proportion of patients with a condition who die from that condition

●

Association measures: o

The risk ratio (or relative risk; RR) is the probability of events in the exposed/treated group divided by the probability of events in the control group

o

The odds ratio (OR) is the odds of events in the exposed/treated group divided by the odds in the control group

Study design The most common study designs are listed by decreasing order of clinical relevance and should be chosen according to the study’s aim: ●

A meta-analysis is a type of systematic review that uses a statistical approach to summarize empirical evidences from published and unpublished studies

●

A systematic review uses a narrative approach to synthesis empirical evidences from published and unpublished studies

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A randomized controlled trial (RCT) is a special type of experimental cohort study whereby the investigator randomizes participants suffering from a disease into >2 groups, assigns them to different treatments (e.g., a drug and a placebo) and follows them prospectively while comparing the treatment’s effect

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In an observational cohort study, the investigator identifies a cohort of interest exposed to a risk factor or a treatment and chooses a control group with a different exposure. These groups are then followed prospectively while comparing the long-term consequences of the exposures. They are particularly relevant for evaluating risk factors of the disease, the prognosis, the incidence and/or risk ratio

●

In a case-control study, the investigator first identifies patients or “cases” afflicted by a disease of interest and then finds a matching control group without the disease. The exposures in each group are then compared retrospectively. They are relevant to identify potential risk factors of the disease and the odds ratio

●

In a cross-sectional study, the investigator measures both the exposure and disease prevalence at a single time point. They are appropriate to generate hypotheses on the cause of disease or to evaluate the odds ratio

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In a case series, the investigator describes several (>3–4) patients with unique clinical presentation that have a high educational value

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In a case report, the investigator describes 1–3 patients with very unique clinical presentation that has a high educational value

Activities

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Webinar 1 – Planning Before You Begin Activity 1 – Defining clear study aims Based on the following research problem:

Problem: Although PD-1 blockade has only shown limited efficacy in patients with glioblastoma, preclinical studies have suggested that the PD-1-programmed deathligand (PD-L1) axis is immunologically relevant and that a therapeutic window exists. Adapted from Nature Medicine

First identify the variable, outcome and sample:

A. Intervention: _____________________________________________

B. Outcome:

_____________________________________________

C. Population:

_____________________________________________

Second, choose which aim is most appropriate.

A. In this study, we investigated if combinatorial blockade of the Na/H exchanger isoform 1 and PD-1 more strongly altered the functional immune landscape and extend the survival in glioblastoma patients compared with PD-1 blockade alone.

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B. In this study, we investigated if neoadjuvant PD-1 blockade altered the functional immune landscape and extend survival in patients with recurrent, surgically resectable glioblastoma. C. In this study, we investigated if salvage therapy with PD-1 blocking antibodies improved the median progression-free survival in patients with recurrent highgrade gliomas.

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Activity 2 – Identifying appropriate study designs Match the study designs on the right with the studies on the left.

In this retrospective study, we investigated the risk

Systematic review

factors associated with the development of hepatocellular carcinoma in chronic hepatitis C patients. In this survey, we compared the prevalence of dental

Randomized controlled trial

caries in children from low and middle income (> or < 10,000 DHS/month) families living in Abu Dhabi. Here, we report the sudden cardiac death in a patient

Cross-sectional study

with advanced hepatocellular carcinoma receiving successful sorafenib monotherapy. In this prospective study, we evaluated the incidence of

Cohort study

acute kidney injury among hepatocellular carcinoma (HCC) patients who had received transarterial chemoembolization (TACE) with HCC patients who did not receive TACE. This study qualitatively assessed the efficacy and safety

Case-control study

of cytokine-induced killer cell-based immunotherapy as an adjuvant therapy for hepatocellular carcinoma from 12 randomized controlled trials. In this study, we evaluated the combinatorial efficacy of

Case report

sorafenib and temozolomide (TMZ) by administering TMZ to one group of hepatocellular carcinoma (HCC) patients receiving sorafenib and placebo to a control group of HCC patients undergoing sorafenib treatment.

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Useful Resources ____________________________________________________________________________

Ethics Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinkiethical-principles-for-medical-research-involving-human-subjects/) Equator Network (www.equator-network.org) Nature – Challenges in Irreproducible Research (www.nature.com/news/reproducibility-1.17552) Nature – Life Sciences Reporting Summary (www.nature.com/authors/policies/ReportingSummary.pdf)

Committee on Publication Ethics (publicationethics.org) WHO Informed Consent Form Templates (www.who.int/rpc/research_ethics/informed_consent/en/)

ICMJE Conflicts of Interest Form (www.icmje.org/conflicts-of-interest) ICMJE – Authorship (www.icmje.org/recommendations/browse/roles-and-responsibilities/definingthe-role-of-authors-and-contributors.html)

ORCiD – Unique identifier for researchers (www.orcid.org)

Clinical Trials ICMJE – Clinical Trial Registration (www.icmje.org/recommendations/browse/publishing-andeditorial-issues/clinical-trial-registration.html)

WHO – International Clinical Trials Registry Platform (www.who.int/ictrp/network/primary/en/) Pan African Clinical Trial Registry (www.pactr.org) ClinicalTrials.gov (www.clinicaltrials.gov)

Statistics Nature – Statistics for Biologists (www.nature.com/collections/qghhqm) BMJ – Statistics Notes (www.bmj.com/specialties/statistics-notes)

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FAQs

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Q What equipment do I need to participate in the webinars?

A You will need a desktop computer, a laptop, or a large-screen mobile device and a good headset for audio. The training will be conducted in English. The Nature Research Academies team also recommends that you print or display this Participant Guide on a separate device during the webinars.

Q How do I join the webinar on the day?

A Joining is easy and just takes a few seconds. Simply click the link in the e-mail invitation to join the webinar at the specified time and date. You’ll proceed to the session immediately. Remember that you will need to have registered before the session begins.

Q GoToWebinar won’t work on my computer or device…

A For information on system requirements for attending a GoToWebinar session, please visit this page: https://www.gotomeeting.com/en-gb/webinar/online-webinar-support

Q I’m not able to register or join the webinar…

A If you have any issues with registration or accessing the webinars, please e-mail [email protected] If you have any other issues or questions regarding the webinars or the Nature Research Academies virtual workshop, please email [email protected]

This material is not to be used outside of the workshop without the consent of Springer Nature.

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