Developments in the field of proton beam therapy (PBT) have recently crossed the tipping point wherein the modality is now more versatile than ever before, with possibilities and likely indications expanding rapidly.However the pace of evidence generation lags behind the developments in the field.Generating quality evidence has its own set of challenges owing to complexities of conducting randomized controlled trials, which are the hallmark of level 1 evidence generation.Here we discuss various challenges to clinical evidence generation in PBT and have suggested certain solutions including collaborative approaches and alternative study designs to mitigate these challenges.