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Help Industry With Clinical Trial Design

Study Protocols

The general design of a study, or the study protocols, can make all the difference when recruiting participants, retaining participants, and collecting meaningful data. Your participation can ensure that clinical trials are designed to be patient-friendly and will provide inclusive data that foregrounds patient concerns. Design elements and types  include:

  • Therapy delivery method:
    • Different therapy delivery methods may each have benefits and drawbacks that can affect whether a patient population will even participate in a study. 
    • For example, intravenous (IV) therapy administration gives dependable and reproducible effects and the dose can be adjusted immediately, which seems to make it ideal for clinical trials. However, if the majority of the patient population consists of children, then a different route might be preferable. 
  • Frequency and duration of therapy delivery:
    • Since you know the patient population well, you can help the Sponsor balance the requirements of treatment frequency and duration of delivery with the patients’ perceived burden of the symptom(s) being treated.
    • The frequency a person must have a treatment can affect their compliance with the clinical trial protocol. For example, due to factors that the Sponsor may not be aware of, the burden of taking a pill multiple times a day 2 hours before or after a meal may make compliance very difficult.
    • The duration of the therapy delivery can also affect compliance, especially in combination with frequency. For example, a therapy that must be delivered slowly over a 6 hour period by IV administration may greatly decrease participant participation unless the frequency is once a week, or possibly monthly.
    • The more burdensome the symptom(s) being treated are perceived by a patient, the more likely a patient will accept higher treatment frequency and longer duration of the therapy administration.
  • Comorbidities: 
    • Sponsors may not be aware of comorbidities that may affect the clinical design. For example, if researchers are designing their clinical trial to require fasting blood work, they may need to redesign the protocol if low blood sugar is a common comorbidity. 
  • Historical controls: 
    • A historical control is an evaluation technique that is used in place of a control group when it would be inappropriate to give a placebo. 
    • It essentially compares previous data, like older clinical trials, to new data. 
    • However, historical control data can be inaccurate or subject to biases, especially when the data was generated before patient input was actively sought by the research community. 
    • Your input and the data from natural history studies can help correct these biases, which will generate more accurate and useful data. 
  • Add-on design:
    • Add-on design is a protocol that gives the therapy being  being studied while currently available treatment is continued. 
    • The control group in this type of design will continue receiving current clinical care and a placebo.
    • This type of design may increase patient participation, especially when stopping current treatment might lead to disease progression or an increase in severity of symptoms.
    • Add-on design may not always be possible. For example, the therapy being studied and the current treatment may be predicted to interact negatively or the combination may increase the risk of adverse effects. 
  • Time-to-event trials:
    • Time-to-event trials can use the attainment of a clinically meaningful worsening of the disease as a primary endpoint. For example, for a disease that progresses to respiratory problems, requiring mechanical ventilation can be a primary endpoint. 
    • Increased time to reach the event demonstrated in participants in the experimental trial can support the ability of the therapeutic approach to slow the progression of the disease.
    • Participants can be transitioned to open-label extension upon reaching the event.
  • Open-label extension:
    • This is a new, separate clinical study that may be available to participants after they have completed an experimental randomized study.  
    • It only includes participants from “parent” experimental studies testing the same therapy.
    • The goal is to gather more long term data on safety and efficacy. Data from this study type is also included in the New Drug Application (NDA) required for the U.S. Food and Drug Administration (FDA) marketing review process.
    • All participants in an open-label extension study receive the therapy, even participants who were previously in the control group. 
    • The availability of an open-label extension study is presented in the informed consent of the original study, but the participant can wait until the end of the study to decide if they wish to participate.
    • Since the researchers of the original study need to remain blind to the control and experimental group assignments until after data analysis, it may be necessary to have a  new study coordinator who is not involved in the original study provide information to the participants that may affect their decision to join the open-label extension. 
    • Timing the start of the open-label extension study must be executed so that treatment doses are not missed.
    • Eligibility for continuation into the open-label extension must also be clearly established.
    • Results of these studies may be biased since participants are self-selected and more likely to have seen positive clinical outcome measures and few, if any, adverse effects if they were in the experimental group.