In the Clinical Trials editorial Salim Yusuf writes combined effort by stakeholders “is urgently needed to reverse the harm that the current ICH (International Conference of Harmonisation) GCP (good clinical practice) guidelines have caused”.
Without this therapeutic progress “will be severely slowed down”, “scarce funds” will be wasted and initiating multi-site trials will remain “a formidable, expensive and time-consuming process”.
Failings in GCP stem from “the lack of formal, early, and integral involvement of the academic and clinical investigator community”. Without this input regulators created guidance that fails to understand what aspects of a trial matter, writes Yusuf, while placing burdens on investigators.
“[ICH GCP guidelines] have created a byzantine maze of bureaucratic steps that emphasise relatively unimportant issues, leading to waste, obstructing the conduct of well-designed important trials, and impeding scientific progress”, writes Yusuf.
These issues have been created without harmonising trial initiation approval, according to Yusuf, and it is questionable whether “GCPs are ‘good’, ‘clinically relevant’, or ‘practical’”.
Standardisation & multi-centre trials
Yusuf covers specific failings of GCP guidelines. Firstly, the need for precise standardisation of processes and procedures is, according to Yusuf, made redundant by randomised controlled groups. Consequently, focus should be placed on the “only three issues that matter”.
These are ensuring: concealed randomisation and inclusion of all randomised patients in the analysis; enough events to minimise random errors; and unbiased ascertainment of outcomes. A simplified approach, focused on these elements, would cut costs, writes Yusuf.
Global multi-centre trials expose another regulatory failing, according to Yusuf, because one protocol must be reviewed by many ethics committees. Minor variations between jurisdictions have made initiating multi-site trials “a formidable, expensive and time-consuming process”.
To resolve these issues “one single rigorous review by a reputable international group should be adequate and accepted by all centres and regulators”, writes Yusuf.
Insurance & adverse events
The adverse event (AE) definition is, in practical terms, “neither sensitive nor specific, and can be compared to searching for a ‘needle in a haystack’”, according to Yusuf. To fix this Yusuf says AEs should be only classified as such after a threshold, such as dose reduction, is crossed.
Finally, the lack of distinction between Phase III and Phase IV trials in insurance requirements can place a “huge burden” on studies “where the risks to patients are negligible”, writes Yusuf.
Yusuf recommends adoption of a risk-based approach that places more demands on early phase trials of new interventions. This should be an international effort that brings together different stakeholders.
“If this is not done, progress in the battle against disease will be severely slowed down and much of the scarce funds available for clinical trials will be wasted. Our patients deserve better. We should demand no less”, ends Yusuf.