MD250 EPIDEMIOLOGY
Scenario 1: In order to evaluate the efficacy and safety of a new non-steroidal anti-inflammatory drug (NSAID) a randomized control
trial (RCT) is proposed as a means to obtain the food and drug administration’s (FDA) approval. Randomization has the advantage to
non-randomized studies that it makes the groups comparable to both known and unknown factors that otherwise would affect the
outcome. A disadvantage is that RCT is expensive and time consuming and some would argue its artificial conditions that are difficult
to apply to real life. In addition there’s ethical limitations where one cannot guarantee the placebo group getting equal treatment, in
addition informed consent to intervention (the exposure) is impossible. The exposure of the study is the NSAID in appropriate
concentration based on the bioavailability and pharmacological properties. The outcome for this study is pain relief to document
efficacy and adverse effects to document safety. After consulting the FDA on information to which phase of testing the drug has
reached, the size of the study population is then selected accordingly. FDA study population ranges from 20-30, 100-300, 3000 and
several thousands volunteers in the first-, second-, third- and fourth-phase respectively [1.1-4]. FDA informs the drug has reached
phase three, and a study population of 3000 is set to be recruited amongst orthopedic postoperative patients at several hospitals,
excluding patients with comorbidities and comedications. Pain relief would be measured at the first follow up appointment by
VAS-scale and adverse effects documented by standardized electronic form. The subjects are randomized to two groups where one is
offered the new drug and one is offered placebo. The method of the study should be clearly standardized, ethically evaluated, in
accordance with good clinical practice (GCP) and FDA guidelines. Results of RCT are considered gold standard and can be presented
when marketing the new drug to clinicians.
Scenario 2: Commissioned by the Ministry of Labour a cross sectional study is proposed to investigate if exposure to inhaled toner
dust (from photocopiers or laser printers) can cause lung cancer (outcome) and recommend potential regulations needed to protect the
workers. Considering the relatively limited budget provided, a cross sectional study is proposed and it has the main advantage of
being affordable in addition it can investigate several outcomes and exposures. However it requires a clearly defined study population
to provide reliable results on causality to generalize the results. A study population of 500 subjects are recruited from the toner (e.g.
industry, manufacturing, maintenance and recycling). Excluding smokers, subjects with chronic conditions or those that had less than
1 year exposure to toner dust. Of the remaining subjects those regularly exposed to toner dust served as the control while the rest
served as controls. Informed consent is obtained from each subject. A survey 2 times a month for a 2 year period is conducted to the
workers for medical history, the survey would be evaluated by an ethical committee. Regarding measurement of the exposure, air
samples would be collected from specific locations in the workspace and analyzed for mutagens. Similarly the exposure would be
analyzed from each individual subject by blood samples.
Scenario 3: In order to assess the prevalence of long COVID symptoms with focus on absenteeism from work, among adults in
working age, a retrospective cohort study of 6 months is proposed as a response to the commission by the Ministry of Health. Since
the data would be collected from electronic health records (EHR) the main advantage is that the exposure is recorded before the
outcome and temporality is preserved, another advantage is minimization of recall bias. The main disadvantage about EHR is that
many different health care providers are involved in treatment of the patient, this would reflect on the data as less accurate. The
subjects would be recruited amongst COVID-19 survivors collecting the data from EHRs making it possible to include a large number
of subjects, specifically five hundred thousand adults of working age. The outcome would be assessed by obtaining sick leaves
prescribed from a general practitioner, excluding subjects with conditions that would increase the risk of contracting COVID-19 (e.g.
immunocompromised, cancer patients, asthmatics, chronic lung disease, diabetics and morbidly obese). However the excluded
vulnerable subjects would be interesting to analyze and compare the data in order to recommend guidelines.
References:
(1) U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for
Biologics Evaluation and Research (CBER) Office of Regulatory Affairs (ORA) (2008). Guidance for Industry CGMP for Phase 1 Investigational
Drugs. [online] Available at: https://www.fda.gov/media/70975/download.
(2) Reynolds, K. (n.d.). Clinical Pharmacology 2: Clinical Pharmacology Considerations During Phase 2 and Phase 3 of Drug Development.
[online] Available at: https://www.fda.gov/media/84924/download.
(3) U.S. Department of Health and Human Services Food and Drug Administration (2017). 22 CASE STUDIES WHERE PHASE 2 AND PHASE 3
TRIALS HAD DIVERGENT RESULTS. [online] Available at: https://www.fda.gov/media/102332/download.
(4) U.S. Department of Health and Human Services Food and Drug Administration (2019). Step 3: Clinical Research. [online] Fda.gov. Available
at: https://www.fda.gov/patients/drug-development-process/step-3-clinical-research#Clinical_Research_Phase_Studies.
Scenario 1: In order to evaluate the efficacy and safety of a new non-steroidal anti-inflammatory drug (NSAID) a randomized control
trial (RCT) is proposed as a means to obtain the food and drug administration’s (FDA) approval. Randomization has the advantage to
non-randomized studies that it makes the groups comparable to both known and unknown factors that otherwise would affect the
outcome. A disadvantage is that RCT is expensive and time consuming and some would argue its artificial conditions that are difficult
to apply to real life. In addition there’s ethical limitations where one cannot guarantee the placebo group getting equal treatment, in
addition informed consent to intervention (the exposure) is impossible. The exposure of the study is the NSAID in appropriate
concentration based on the bioavailability and pharmacological properties. The outcome for this study is pain relief to document
efficacy and adverse effects to document safety. After consulting the FDA on information to which phase of testing the drug has
reached, the size of the study population is then selected accordingly. FDA study population ranges from 20-30, 100-300, 3000 and
several thousands volunteers in the first-, second-, third- and fourth-phase respectively [1.1-4]. FDA informs the drug has reached
phase three, and a study population of 3000 is set to be recruited amongst orthopedic postoperative patients at several hospitals,
excluding patients with comorbidities and comedications. Pain relief would be measured at the first follow up appointment by
VAS-scale and adverse effects documented by standardized electronic form. The subjects are randomized to two groups where one is
offered the new drug and one is offered placebo. The method of the study should be clearly standardized, ethically evaluated, in
accordance with good clinical practice (GCP) and FDA guidelines. Results of RCT are considered gold standard and can be presented
when marketing the new drug to clinicians.
Scenario 2: Commissioned by the Ministry of Labour a cross sectional study is proposed to investigate if exposure to inhaled toner
dust (from photocopiers or laser printers) can cause lung cancer (outcome) and recommend potential regulations needed to protect the
workers. Considering the relatively limited budget provided, a cross sectional study is proposed and it has the main advantage of
being affordable in addition it can investigate several outcomes and exposures. However it requires a clearly defined study population
to provide reliable results on causality to generalize the results. A study population of 500 subjects are recruited from the toner (e.g.
industry, manufacturing, maintenance and recycling). Excluding smokers, subjects with chronic conditions or those that had less than
1 year exposure to toner dust. Of the remaining subjects those regularly exposed to toner dust served as the control while the rest
served as controls. Informed consent is obtained from each subject. A survey 2 times a month for a 2 year period is conducted to the
workers for medical history, the survey would be evaluated by an ethical committee. Regarding measurement of the exposure, air
samples would be collected from specific locations in the workspace and analyzed for mutagens. Similarly the exposure would be
analyzed from each individual subject by blood samples.
Scenario 3: In order to assess the prevalence of long COVID symptoms with focus on absenteeism from work, among adults in
working age, a retrospective cohort study of 6 months is proposed as a response to the commission by the Ministry of Health. Since
the data would be collected from electronic health records (EHR) the main advantage is that the exposure is recorded before the
outcome and temporality is preserved, another advantage is minimization of recall bias. The main disadvantage about EHR is that
many different health care providers are involved in treatment of the patient, this would reflect on the data as less accurate. The
subjects would be recruited amongst COVID-19 survivors collecting the data from EHRs making it possible to include a large number
of subjects, specifically five hundred thousand adults of working age. The outcome would be assessed by obtaining sick leaves
prescribed from a general practitioner, excluding subjects with conditions that would increase the risk of contracting COVID-19 (e.g.
immunocompromised, cancer patients, asthmatics, chronic lung disease, diabetics and morbidly obese). However the excluded
vulnerable subjects would be interesting to analyze and compare the data in order to recommend guidelines.
References:
(1) U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for
Biologics Evaluation and Research (CBER) Office of Regulatory Affairs (ORA) (2008). Guidance for Industry CGMP for Phase 1 Investigational
Drugs. [online] Available at: https://www.fda.gov/media/70975/download.
(2) Reynolds, K. (n.d.). Clinical Pharmacology 2: Clinical Pharmacology Considerations During Phase 2 and Phase 3 of Drug Development.
[online] Available at: https://www.fda.gov/media/84924/download.
(3) U.S. Department of Health and Human Services Food and Drug Administration (2017). 22 CASE STUDIES WHERE PHASE 2 AND PHASE 3
TRIALS HAD DIVERGENT RESULTS. [online] Available at: https://www.fda.gov/media/102332/download.
(4) U.S. Department of Health and Human Services Food and Drug Administration (2019). Step 3: Clinical Research. [online] Fda.gov. Available
at: https://www.fda.gov/patients/drug-development-process/step-3-clinical-research#Clinical_Research_Phase_Studies.
