INTERVENTIONAL STUDY

DESIGNS

Kiran Mishra
MSc Part II
Sem 3 Paper 1
009
 INTRODUCTION TO RESEARCH DESIGN

• What is research design?

• Why is research design important?

• Classification of study designs - Observational and interventional studies

• Role of the researcher

 INTERVENTION STUDY DESIGNS

• Also known as Experimental study designs

• What is an intervention design?

• Test group, control group

• Where are experimental study designs used?

- To establish Causal Relationship
- To compare the effects of multiple drug/treatment
TYPES OF INTERVENTION STUDY DESIGNS
 RANDOMIZED CONTROL TRIALS (RCT)

• Two groups – Control and test/treatment.

• Both groups are randomized

• Intervention and placebo/sham procedure

• Unbiased study
• Example:
-A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19 (effect of dietary
supplements on symptom course and quality of life in patients)
- 3 arm study –
1. Control group (n=34)
2. Vitamin C – 1000mg (n=32)
3. Melatonin – 1o mg (n=32)
- All supplements taken for 14 days

- Conclusion of the study :

Vitamin C 1000 mg once daily has no effect on disease progression. Melatonin 10 mg daily may have a statistically
significant effect but it is unclear if this represents a clinically significant benefit to those with mild-to-moderate
symptoms of COVID-19 infection. Further study is warranted.
 HOW IS RANDOMIZATION ASSURED?

• Allocation concealment

• Blinding

• Compliance

• Co-intervention
 NON RANDOMIZED RCT

• Prone to bias

• No randomization

• Depends on researcher/patient

• Results aren’t too valid.

• Example: Effects of Oral Multi-Vitamin Multi-Mineral Supplement Formulations on Laboratory Outcomes and Quality
of Life
- Three-arm non-randomized controlled trial.
- A total of 72 healthy adult individuals with total serum 25-(OH)D level of 20–29 ng/ml were invited to choose from the
three available options
(1) Hydro-Cell-Key (HCK®, Hepart AG, Switzerland) –
a) vitamin D3 2,000 IU,
b) vitamin C 1,000 mg,
c) vitamin E 166 mg,
d) vitamin A 1 mg,
e) coenzyme Q10 30 mg,
f) natural carotenoids 8 mg, and
g) citrus flavonoids 200 mg in granule formulation
(2) VTL-7 (VWSC) contains similar vitamins and minerals but in capsule formulation
(3) Placebo capsule (no supplement)
• Conclusion: The supplements of MVMM in capsule formulation increased the serum
levels of some micronutrients to a higher extent than that of granule formulation.
Participant adherence remains a potential confounder and should be further explored.
 CLUSTER RANDOMIZED TRIALS

• Cluster of similar people.

• Requires special statistical analysis

• Example: Implementation Evaluation of a Cluster Randomized Controlled Trial to Promote the Use of Respiratory
Protective Equipment Among Migrant Workers Exposed to Organic Solvents in Small and Medium-Sized Enterprises
(SMEs)

- 60 SMEs -> random allocation to a low- or high-intensive intervention group, or a control group.
- The low-intensive intervention group was subjected to both traditional and Health occupational health education.
- The high-intensive intervention group was subjected to the low-intensive group activities and peer education.

- Conclusion: A multi-component occupational health intervention to promote the use of RPE among workers in SMEs was
feasible and acceptable. Peer education had great potential to enhance implementation of use of RPE.
 FACTORIAL DESIGNS

• allows the study of two interventions in the same trial without unduly increasing the required number of participants.
• Allows study of interaction between both the interventions

• Example
- In a study, infants in south India being administered a rotavirus vaccine were randomly assigned to receive a zinc
supplement and a probiotic, only probiotic (with zinc placebo), only zinc supplement (with probiotic placebo), or neither
(probiotic placebo and zinc placebo)

- Conclusion:
- Neither zinc nor probiotic led to any change in the immunogenicity of the vaccine
- The group receiving the zinc-probiotic combination had a modest improvement
 CROSSOVER STUDY DESIGN

• A special type of study designs – participants intentionally crossover to the other arm
• Washout period between the crossover

• Advantages:
• Self controls
• Compensation for failed randomization.

• Limitations:
• More advantageous over RCT but is not possible in all conditions (if disease is curable)
• Example:
-In healthy adults resistant maltodextrin produces a greater change in fecal Bifidobacteria counts and increases stool wet
weight: a double-blind, randomized, controlled crossover study.
- 51 participants were randomized to consume
0g of RMD (25g of maltodextrin)
15 g RMD (15 g RMD and 10 g maltodextrin) and
25 g RMD
- Followed by a 2-week washout.
- Participants collected all stools for 2 days at weeks 0 and 3 of each intervention for stool wet weight (WW)
measurements and fecal Bifidobacteria counts.

- Conclusion: RMD was well tolerated and allowed individuals who typically consume an inadequate fiber diet to exceed
recommendations for total daily fiber intake. Gastrointestinal symptom data suggested that both 15 g and 25 g of RMD
were fermented, whereas only 25 g of RMD resulted in a greater change in Bifidobacteria and an increase in stool WW.
 PRETEST POSTTEST DESIGN

• Aka Pre-post or before after studies.

• No control arm
• Causal relationships can’t be established.
• Basis of deriving a conclusion - the temporal relationship of the measurements to the intervention
• Variable of interest is measured before and after an intervention in the same participants
• Example - Etramp5 as a useful serological marker in children to assess the immediate effects of mass drug campaigns
for malaria.

- Study Design:
- 25 schools – with at least 100 students per school who are available to take the intervention, and are regularly enrolled in
the school.
- Children self reported who all took part in the mass drug administration campaign.
- Control was also done on the basis of children who denied participation in the mass drug campaign

- Conclusion:
-> In the present cohort of Haitian children, antibody responses against ETR51 were rapidly affected by a tMDA campaign
using primaquine.
-> Seropositivity to ETR51 was significantly reduced in the 2–6 weeks following the intervention, confirming its usefulness
as a short-term marker in child populations.
 INTERVENTIONAL STUDIES WITHOUT CONCURRENT CONTROLS

• No control arm in the study at the present moment.

• Historical Control

• Liable to high risk of bias

 LIMITATIONS OF EXPERIMENTAL STUDIES

• Design is limited to the testing population, variations are expected across the globe.

• Artificial settings of experiments may alter the behaviours or responses of participants

• Cost if special equipment or facilities are needed

• Limitation to carrying out an experiment due to ethical reason.

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