Due to a new study design for clinical trials, more ALS patients are eligible to participate. This has been shown by recent research. Selecting patients differently and adapting the trial design, results in several benefits for both patient and researcher.
Research on ALS treatments is as vital as ever, but is difficult because of the different variations of the disease. This also means that finding suitable participants for research is not always easy. Participants quickly fail to meet the selection criteria. This may change with a new, innovative research design. The European Medicines Agency (EMA) has already endorsed these innovations. In the current study researchers from the ALS Center and TRICALS demonstrate the effectiveness of the design.
Selection criteria for patients
To determine which patients are eligible for participation in a study, a number of selection criteria are established in advance (classic study design). These include age, prognosis and lung function. Patients must meet all these criteria to be included in the group of “suitable” candidates for a particular study. The disadvantage of this method is that people are sometimes excluded on one criterion – for example, age – while they otherwise meet all the conditions. Thus, people are excluded even though they are technically suitable. The number of suitable patients is therefore often very low.
Prediction per patient
To solve this problem, the researchers propose to stop only looking at these selection criteria and instead use a predictive computer program. Risk-based patient selection provides a prediction per patient based on criteria outcomes. A so-called individual risk profile. It is then determined within which scores the risk profiles must fall in order to participate in the study. Thus, this method no longer looks at individual selection criteria but at someone’s complete profile. This creates a larger and more suitable target group of participants. As a result, more patients are eligible for drug research, where this would not be the case with a classic research design.
Another additional advantage of using risk profiles is that the results of research can be better generalized. This means that the results are applicable to a higher variety in patients, because a more diverse group of patients participated in the study.
To further optimize drug research for ALS, in addition to the selection criteria, the researchers propose a flexible research design. This means that the framework of the study can be gradually adjusted.
Normally, the duration of a study is determined in advance. Afterwards, the data is analyzed and the researchers see whether the medication had an effect or not.
In this new, flexible design, there is no fixed duration for the study and the effects of the medication are already examined during the study. By analyzing the data during the study, researchers can react more quickly to the effects they see in the patients in response to the medication. This allows them to stop the study when it is necessary; as soon as they can show that the drug is working correctly or not. Both scenarios save a lot of time for patients; if the drug doesn’t work, patients can participate in other studies faster; if the drug does work, patients who were given the ‘fake’ medication (placebo) during the study can get the real medication faster.
Advantages and disadvantages
By using this flexible design, fewer participants will be needed, the duration of the study will be shorter on average, participants will generally be exposed to the placebo for less time, and costs will be lower.
Individual patients may have longer exposure to the placebo if the drug proves to be effective, but shorter if the drug is ineffective.
This study was financed by the Stichting ALS Nederland, UK Motor Neurone Disease Association (MNDA) and ALS Liga België. The study is part of the Europese Joint Programme – Neurodegenerative Disease Research project (JPND).