Those of us who have seen the movie, ‘The Life of PI’, would agree that the boy, Piscine Molitor Patel or PI had to go through a lot before emerging a winner. What cannot be cured, must be endured.
When one reads about the current scenario as far as Clinical Trials (CTs) are concerned, the Principal Investigator or PI must be also wondering why he is being made to go through so much. All that he or she has done is evaluate a new drug in the best interest of his/her patient. Why is he/she then, being labeled an interested party?
Yes he is interested in his patient’s welfare and in the true spirit of equipoise conducts the informed consent process, screens, and then determines eligibility of the patient, before randomizing the patient to one or the other arm of the trial, with the full comprehended consent of the patient.
Yet in some cases the PI is being pilloried. Patients are being instigated to say that informed consent was not administered as a process, and that they are being made to sign on a piece of paper without even reading or understanding the same.
What is the PI to do in such cases? Have a witness to this process? The basis of the doctor-patient relationship, be it in clinical practice or in a clinical trial, is trust. Do we want video camera recordings to breach this trust and confidentiality, all because some people don’t believe that informed consent is being administered as a process? Should ethics committee members conduct surprise checks as part of their oversight responsibility?
What is in it for the PI? What does he get after putting in painstaking hours for the trial, over and above his busy practice? Such allegations, which affect his credibility and that of clinical trials in general? Does he get money for doing a trial?
He receives an investigator grant. But that is for the conduct of the trial. To pay for the free treatment of his patients including all tests, procedures, and for managing adverse events. To pay his staff who support him in the conduct of the trial over and above their day job. To ensure drug supply is carefully stored and accounted for. To ensure that processes are and documentation is perfect for the clinical research associate, quality standards manager, auditor, and inspector. To ensure that patient rights, safety and confidentiality are maintained. To ensure that data on the case report form is accurate and verifiable from source documents.
The PI needs to be trained in good clinical research practice and then train his staff. He can delegate but can never abdicate. The ultimate responsibility is his. Whose trial is it anyway? Whose data is on the case report form? Who conducts the trial and manages patients? Every “participant” in a clinical trial is equally responsible, viz., the patient, the doctor, the ethics committee, the regulator, and the sponsor.
Sometimes the PI may also be part of a protocol development team and needs to be especially well versed with all aspects of the drug and design of the study to ensure it is globally and locally relevant.
The PI is at the center of the patient’s universe. Everything revolves around him. Not everyone can be a PI. One needs to not only be qualified by knowledge, training and experience but one also needs to have trained staff, a CR secretariat so to speak, space, time and the mindset of documentation and process (“if it has not been documented it has not happened” – Sir Antoine el Hage, ex-US FDA Commissioner).
He must be trained in the onerous task of not just being vigilant for unexpected adverse events and managing the same, but also in using his clinical acumen for judging whether an adverse event is causally related to the study or drug. This has important implications as the case may then be compensable per section 2.4.7 of the Indian GCP guidelines.
To be fair to the sponsor, the PI should engage the sponsor in a dialogue before determining causality. The current compensation guideline can be misused and can threaten the future of all CTs in India, even investigator-initiated trials.
Just like in the movie, the life of a PI is now as scary since he is adrift on a boat in an uncharted sea of suspicion, with the tiger of media scrutiny and judicial inquiry, not knowing what can happen next. Testing his resilience like never before. Wondering when will this mental torture end. And what has he done to deserve all this? ‘Why me?’, must be his constant refrain to God. When all he wanted was for his patient to get better.
He has taken this risk for his patient. Because the current standard of care was not good enough for his patient. He has tried to make the patient as safe as he could. He has followed the principles of GCRP in spirit and to the letter. He has subjected himself to the constant monitoring, data clarification, audits and inspections, all for his patients. And yet he gets this in return? From taking the oath of Hippocrates to being labeled a Hypocrite?
Why should he continue to do this? Better to go back to doing only clinical practice. No point in being a principal and principled investigator. Let trials not happen in India. Let new drugs not come to this country. Let patients in India compromise their health by sticking to status quo. Those who can afford will go abroad. Those who can’t afford will have to die here, denied of their only hope for survival.
Yes, “uncontrolled” CTs can play havoc with patients’ lives. It is perhaps the turn of the PI to counter-litigate in patient/public interest. The question is not whether we can afford to let CTs happen in India. The question is whether we can afford not to have CTs happen in India.
This is a guest column by Dr. Viraj Suvarna. These are Dr. Suvarna’s thoughts in his personal capacity and not as an employee of Boehringer Ingelheim India Private Limited where Dr. Suvarna serves as Medical Director.