Risk Analysis in Clinical Trials-Overview

Risk Analysis in Clinical Trials-Overview

 

What Is Risk Analysis?

Risk Analysis is the process of determining the significance of risks. The result of the risk evaluation technique is an update to our risk register showing the priorities of the risks. Using risk thresholds to determine which risks are urgent and require treatment.

There are many ways to analyze risks. We can simply assign a Low, Medium, or High rating for each risk.  A better method is to evaluate the probability (likelihood) and impact (consequence) of each risk, assigning a numeric rating such as 1 to 5, 5 being the highest.

When to Evaluate Risks

Should start evaluating risks early in their projects; should continue evaluating risks in an iterative until the project is completed.

Importance:

Inspection cost us money, but what are our risks without the inspection? A few years later. Imagine the inconvenience, the amount of time, and the cost to replace the data/things.

There is always a cost of risks, now and later. We have the cost of managing risks such as the time for identifying and evaluating risks. There’s the cost for treating risks — the responses to mitigate threats and exploit opportunities. And there’s the cost of responding to issues (events that have occurred such as the termites that have destroyed your floor).

Risk Analysis involves Qualitative and Quantitative risk analysis. Qualitative analysis involves simple methods for quickly rating and prioritizing your risks. Quantitative analysis is a numeric analysis that requires more time but provides more data to aid in making decisions.

Qualitative Risk Analysis

1.      KISS (Keep It Super Simple) Method,

2.      Stacked Ranking Method

3.      Probability/Impact Method

1. KISS (Keep It Super Simple) Method

KISS (Keep It Super Simple) Method on small initiatives and projects and with teams that lack maturity in assessing risks. This one-dimensional technique involves rating risks as:
Very Low, Low, Medium, High, Very High

2. Stacked Ranking Method

The Stacked Ranking Method is quick, simple, and is a great method to use with teams. First, the team identifies and captures the risks on Post It Notes that are placed on the wall randomly. Second, the facilitator asks the team, “Which risk is greatest?” The facilitator places the risk in a space on the wall by itself.

The facilitator continues, “What is the next highest risk?” and places the selected risk under the first. The process continues until all the risks have been placed in rank order. If you like, you can write a number on each Post It Note to indicate the order (e.g., 1 on the top risk, 2 on the second highest risk, etc.).

3. Probability/Impact Method

This two-dimensional technique is used to rate probability and impact and may be used to evaluate enterprise, department, and project risks. Probability is the likelihood that a risk will occur. Impact is the consequence or effect of the risk, normally associated with impact to schedule, cost, scope, and quality. Rate probability and impact using a scale such as 1 to 5.

Once you have rated each risk, calculate the risk score as follows:

Probability x Impact = Risk Score

Risks for Conduction of Clinical Trials in Oncology Indication

1) Subject Enrollment- Probability is 5 and Impact would be 3

2) Subject Retention- Probability is 4 and Impact would be 5

Example:
Patient Enrollment: 5 x 3 = 15
Patient Retention: 4 x 5 = 20

Sort the risks in descending order with the risk score as the primary sort. in this case Subject Retention would be the highest risk for this Clinical Trial.

Quantitative Risk Analysis

High temperature describes your temperature in qualitative terms. If it says temperature is 104 degrees Fahrenheit, then it is quantitatively terms.

Example: There is a 30% chance that site will be 10 days late in enrolling the subjects.”

While qualitative analysis takes less time, it is subjective. Quantitative analysis requires more time and effort, but it provides more detailed information.

When to Perform Quantitative Risk Analysis

The example above illustrates a case of when quantitative risks analysis was needed — it allowed the project sponsor to make a more informed decision than was possible with the qualitative risk analysis. The quantitative analysis also allowed the project manager to make better decisions about which risks merited a response.

For large, complex projects, project managers may create contingency and management reserves for their schedule and their budget. The quantitative risk analysis allows the project managers to demonstrate and justify the need for the reserves.

 

Analyzing the Highest Risks with Examples

The team rated these six risks quantitatively as follows:

Risk A. There is a 30% probability that the training time will require an additional 10 days.

Risk B. There is a 40% probability of adding an additional quality assurance member and decrease internal audit time by 20 days.

Risk C. There is a 50% probability that the Electronic Data Capture vendor will implement a required upgrade that will require an additional 20 days.

Risk D. There is 30% probability of the stakeholders asking for additional software features that will require an additional 30 days.

Risk E. There is a 25% probability that the Protocol design will be able to leverage another set of code that will reduce the coding time by 20 days.

Risk F. There is a 70% probability the stress testing will result in the need for an additional database work that will require an additional 40 days.

Notice that Risks B and E are opportunities while rest are Threats.

Expected Monetary Value (EMV) to calculate the contingency reserves which account for the unknown amount of rework. For those of you who may hate math, it does not get any easier than this.

EMV = Probability x Impact.

 

Should add total of 37 days of contingency reserves to the schedule for “known-unknowns”. If desired, we may also add management reserves intended to address “unknown-unknowns”.

Quantitative Tools and Techniques

Quantitative risk analysis tools and techniques include but are not limited to:

        I.            EMV is a statistical concept that allows project managers to calculate the average outcome when the future includes scenarios that may or may not happen. (Although the EMV sounds complex, it’s not difficult to perform.)

      II.            Three-point estimate used to determine the expected result using three estimates: pessimistic, optimistic, and most likely. Expected value = (Pessimistic + 4 (Most Likely) + Optimistic) / 6.

    III.            Modeling and simulation- some project managers use the Monte Carlo technique to perform simulations of the project uncertainties.

    IV.            Sensitivity analysis-this technique helps to determine which risks have the most potential impact on the project objectives.

      V.            Decisions tree used when choosing among different options. Considers future events and aids in making decisions by taking into account risks, probabilities, and impacts.

Putting the Pieces Together

Should always use qualitative risk analysis — it’s quick and can save lots of time and money which  allows team to prioritize their risks quickly and determine which risks merit attention.

The quantitative risk analysis is not always required. When you need more detailed information for large complex projects, pick and perform appropriate quantitative techniques. The quantitative analysis will require more time than the qualitative analysis. It will help you make more informed decisions. 

"If you do not actively attack the risks, they will actively attack you." --Tom Gib

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