Oncology Interview Questions

NOTE: It is not expected that interviewer should ask all the questions, as there are too many questions
for a 1 hr. phone interview. Many of the trailing questions are just offered as alternative questions. It is
expected that interviewer will have time to ask around 15-20 questions.

Question SDTM Oncology domains

1) Which SDTM Domains were developed specifically with Oncology in mind?

TU, TR and RS

2) Describe the contents of Oncology specific SDTM Domains.

The Tumor Identification (TU) – This domain represents data that uniquely identifies a tumor for
continual tracking purposes.

The Tumor Response (TR) – This domain represents quantitative measurements and/or qualitative
assessments of the tumors identified in the TU domain. These measurements are usually taken at
baseline and after that at each subsequent visit to support response evaluations.

The Disease Response (RS) – This domain represents the response evaluation(s) determined from the
data in TR, and data from other sources (in other SDTM domains, e.g. LB) might also be used in an
assessment of response.

3) What variables do you use to merge TU and TR?

TU  TULNKID/ TR  TRLNKID pair is used to relate an identification record in TU domain to

assessment records in the TR domain. It’s more like a point to point linkage. All new tumors are to be
represented in TU and TR domains correspondently;

4) How can you merge TR and RS datasets?

TRLNKGRP/RSLNKGRP pair is used to relate records in the TR domain to a response assessment
record in RS domain, usually link the record having RSTEST=“Overall Response” in the RS to TR as a
one to many linkage.
Question on Oncology Endpoints

5) What is a clinical endpoint?

In a clinical trial, endpoints are the key measure to assess the clinical benefit of the treatment to
patients.

6) Name some oncology endpoints?

- Overall Survival - The percentage of people in a study or treatment group who are still alive for a
certain period of time after they were diagnosed with or started treatment for a disease, such as
cancer.
- Progression Free Survival: Time from randomization until progression, or death from any cause in
the absence of progression
- Objective Response Rate: rate is defined as the number (%) of patients with a best objective
response of CR or PR
- Disease Control Rate: the number (%) of patients with a BOR of PR or CR at any time in the study,
or SD at X weeks, prior to any PD event
- Duration of Response: Duration of response will be derived for those patients who had a best
objective response of CR or PR only.
- Change in Tumor Size: Tumor size is the sum of the longest diameters of the target lesions.
- Time to Tumor Progression: Time from randomization until radiological tumor progression
- Disease Free Survival: Same as PFS but it assumes patients are disease-free at study entry. The
length of time after primary treatment for a cancer ends that the patient survives without any
signs or symptoms of that cancer.

7) Name some Time-To-Event endpoints for oncology trials?

Overall Survival (OS)

Time to Progression (TTP)
Progression Free Survival (PFS)
Time to Progression (TTP)
Time to Clinical Progression (TTPc)
Time to Treatment Failure (TTF)
 Duration of Response (DR)
Duration of Stable Disease

8) RECIST 1.1 target lesions have 4 key visit responses. Can you name them?

CR- Complete Response.

PR-Partial Response.
SD-Stable Disease.
PD-Progressive Disease.

9) Can you give a brief explain of how they are defined? You do not need to give a detailed technical explanation,
just explain in your words what the visit responses mean. Correct

Oncology Trials

10) Why do we have event driven analysis in Oncology?

In non-Oncology trials, endpoint is related to a specific visit. E.g. patient is responder/non-responder at week 24.
However, Oncology endpoints are event based. Time to disease progression, or time to death, are not related to
a specific visit. So Oncology trials are stopped based on events, for example 60% of patients have disease
 progression.

11) How is oncology different than other therapeutic areas?

- CTC Grade
- Oncology trials have Cycles instead of visits for chemotherapy. Most TAs have visits.
- The oncology clinical trials CRF and data sets are relatively complex
- Endpoints are more complex than most other TAs
- Event Prediction.

12) Do we use Placebo-alone control in Oncology trials? Why, why not?

Since patients have cancer, it is unethical to give them no treatment, so placebo-alone trial arm is rare. Patient
must at least receive standard of care.

13) How are Adverse Events categorized differently in Oncology trials than in other clinical trials?

In oncology, use the National Cancer Institute grading: Common Terminology Criteria for Adverse Events (CTCAE).
A grade of 1 corresponds to mild, 2 to moderate, and 3 to severe, 4 is a life-threatening or disabling adverse
event, and 5 is a death related to the adverse event. Whereas non-Oncology trials use the severity scoring of
Mile, Moderate and Severe.

14) Can you describe the RECIST Criteria?

Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define when
tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress")
during treatment. The criteria were published in 2000 updated in 2009 and today the majority of
clinical trials evaluating cancer treatments for objective response in solid tumors use RECIST.

15) Is Quality of Life important in Oncology trials? Why?

The cure for many chronic diseases, such as cancer and AIDS, remains elusive. Clinical research
increasingly has focused more on maximizing patient QOL because improvements in survival and
response to treatment have become more difficult to achieve.
16) Can you explain the difference between target lesions and non-target lesions?

Target lesions are the tumors that are measured, they are selected at baseline, they are usually the
largest lesions in an organ however they should be suitable for repeated measurement, this includes
criteria such as easy to identify. The longest diameter will be measured for each target lesion and the
sum of longest diameters will be calculated. Non target lesions are all other lesions.

17) When Oncology trials have Chemotherapy as part of treatment, such trials are cycle based. Whereas
most other trials are visit based. Can you please describe the difference?

For most non-Chemotherapy trials, drug is administered at a specific dose for each visit. When
Oncology trials include chemotherapy as part of treatment it is administered in cycles. A cycle is
course of treatment that is repeated on a regular schedule with periods of rest in between.

Questions about Tables in Oncology Trials

18) You have just received an Oncology Time-To-Event table and have been asked to validate it. How would
you go about doing that? What kind of things would you look for? What are common errors in such
tables?
If time permits you can also ask the following questions

Statistical questions about Oncology Trials

19) What does a Kaplan-Meier Graph tell us?

The Kaplan- Meier (KM) curve is a graphical representation of a Time to Event analysis showing when
a patient reaches a Progression free survival, duration of response or overall survival.

20) What kind of graphs do you produce in an Oncology study?

Waterfall plots (tumor reduction), forest plots, Kaplan-Meyers plots (Survival)

Duration of treatment figure:
Mean (SD) Max % Platelets Change by Cohort
Graph for Duration of Worst Grade Treatment-Emergent AE (SOC) by Patient
Skyline plots: Hazard ratio

21) When do we censor?

In Time-To-Event analysis, when event does not occur during trial, it is censored.

22) In Oncology, we use Survival Analysis. What is it?

In clinical trials, the effect of an intervention is evaluated by measuring the number of patients
survived after that intervention over a period of time. The time starting from a defined point (e.g
randomization) to the occurrence of a given event (e.g. progression of disease or death), is referred to
as survival time and the analyses group data as survival analyses.

Additional Questions
1) What is Biomarkers in Oncology? Give examples.
A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the
body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the
presence of cancer.

CA-125 is a biomarker used in ovarian Cancer.

The prostate-specific antigen (PSA) biomarker has been widely used to screen men for prostate
cancer

Tumor
Biomarker
Type

ALK
Lung EGFR
KRAS

2) What is the advantage of using biomarkers?

There are clear potential benefits in using biomarkers. Information can be obtained earlier, more
quickly, and more cheaply.

Biomarkers are often cheaper and easier to measure than ‘true’ endpoints. For example, it is easier to
measure a patient's blood pressure than to use echocardiography to measure left ventricular
function, and it is much easier to do echocardiography than to measure morbidity and mortality from
hypertension in the long term. Biomarkers can also be measured more quickly and earlier. Blood
pressure can be measured today, whereas it takes several years to collect mortality data. In clinical
trials the use of biomarkers leads to smaller sample sizes. For example, to determine the effect of a
new drug on blood pressure a relatively small sample size of say 100–200 patients would be needed
and the trial would be relatively quick (1–2 years). To study the prevention of deaths from strokes a
much larger study group would be needed and the trial would take many years. There may also be
ethical problems associated with measuring true endpoints. For example, in paracetamol overdose it
is unethical to wait for evidence of liver damage before deciding whether or not to treat a patient;
instead a pharmacological biomarker, the plasma paracetamol concentration, is used to predict
whether treatment is required.

23) What is a DILI?

Drug induced Liver Injury. Drugs used for therapeutic intent may cause serious or fatal liver injury in
 some patients

24) What is Hy’s Law?

Hy's law is a rule of thumb that a drug is at high risk of causing a fatal drug-induced liver injury (DILI)
when given to a large population, if it caused cases of liver injury that satisfied certain criteria when
given to a smaller population.
- >3*upper limits of normal (ULN) of ALT or AST than the control.
- Among subjects showing such aminotransferase (AT) elevations, >3xULN (AT), total bilirubin (TBL)
to ≥2xULN, without initial findings of cholestasis (serum alkaline phosphatase (ALP) activity
<2xULN).
- No other reason can be found to explain the combination of increased AT and serum TBL, such as
viral hepatitis A, B, or C, preexisting or acute liver disease, or another drug capable of causing the
observed injury.

25) What are surrogate endpoints?

A “surrogate endpoints” is an alternative endpoint (e.g. biological markers, physical sign, etc.) that if
validated allows conclusions to be made about the effect of an intervention on a true endpoint (e.g. a
clinical meaningful endpoint), often requiring shorter “observation” period. An example in oncology
is the use of objective response rate (ORR) and progression-free survival (PFS).

Measurement providing early and accurate prediction of both a clinical endpoint, and the effects of
treatment on this endpoint

26) How is Cox Regression used in time to event analysis in Oncology trials?
The Cox regression model provides us with estimates of the effect that different factors have on the
time until the end event. For example, the effect that age, weight, sex etc… might have on the time to
event analysis. The main aim in this model is to understand the HR. The HR takes into account of the
number and timing events, and the time until last follow-up for each patient who has not
experienced an event i.e. has been censored.