The patient-doctor relationship - a relationship between unequals

Today's Straits Times carried an interesting report of  contest in a coroner's court between a mother who is a nurse, and a surgeon. The mother, who had lost her daughter in a liver transplant contended the surgeon provided sub-standard care because she had a spat with the surgeon earlier.

She did not convince the coroner. However, the case highlighted the inherently unequal relationship that exists between a patient (and relatives) and the doctor. Here, every patient is in essentially a subordinated position, and generally hesitant to offend the attending physician/surgeon. This is generally the case, unless the relationship is based on a completely elective and unnecessary procedure, when a more commercial/contractual relationship may apply.

This is why I am concerned about how the physician/surgeon goes about taking consent for procedures. Often the consent is taken by the care giver. In this case, the patient is often afraid of offending the doctor. This unequal relationship very clearly does not create the circumstance when a truly voluntary consent can be obtained. This ethical lapse, also applies to the situation when consent is being sought for participation in a experimental procedure or clinical trial when the researcher or care giver is himself/herself the one administering the informed consent.

The more academic hospitals compound the problem further by expecting patients on admission to consent to giving up rights to tissues and genetic material for research purposes. This consent is often taken at most inappropriate times when the patient and his/her relatives are most dependent and submissive.

The hospital ethics committees applying their very utilitarian logic, obviously do not disapprove of these ethical lapses.

Avandia bites the dust - oh, but not quite...

So the FDA advisory panel has finally come out to put a finger on the antidiabetic drug Avandia. Or has it?

The drug has been under scrutiny since about 2007, and it has been increasingly been associated with increasing risks of heart attacks. Now the FDA says yes the evidence is clear enough for an expanded warning to be included, but not clear enough for the drug to be yanked off the market. GSK, makers of the drug apparently didn't do a good job generating safety data. FDA expert, Dr David Graham was quoted as saying the GSK RECORD trial was "garbage". Furthermore, GSK apparently withheld information, and submitted poor data, including patient deaths, of patients on Avandia. GSK has already agreed to settle over US$400 million of lawsuits.

In the light of all this, the FDA appears to be waffling a whole lot in not wanting to withdraw the drug. Benefits outweigh the risk appears to be the mantra. Certainly the mantra being chanted by GSK sources.

But this is really not the point....

The critical issue should be whether the drug is as effective and as safe than alternative options. A Japanese (Takeda) alternative, Actos currently appears to do the same job but without associations of increased heart attack risks. So Anadia currently stands as a worse option. It is also not a case of patients currently on Avandia being forced out into a vacuum, should the drug be withdrawn. There are safer alternatives.

So FDA's pussyfooting round the issue is hard to comprehend. To what extent one wonders, is this wanting to allow GSK to recover as much of the drug development costs as possible. The bulk of pharma's drug development cost is recovered in the first few decade post registration. Despite falling sales, every year of delay in taking the drug off the market is a big pot on money for the company.

Let's hope other regulatory agencies, including our own HSA, will be a bit less muddleheaded.

Dr Devathasan's run in with the Singapore Medical Council

Dr Devathasan's recent run in with the Singapore Medical Council is being watched with great interest. Although the details are scanty, and the SMC proceedings are not publicly available, you can read about the case here and here.

It is also interesting as one of the chief complainant is apparently a 'professional rival'. Dr Devathasan was supposed to have offered an unproven therapeutic option to a 77 year old woman. Remember Para 4.1.4 of the SMC ethical guideline?

Curious.

A number of questions need answers:

a] How does the SMC decide if a therapy is 'unproven'. I have pointed out in previous postings that many doctors offer unproven therapies, in the form of off-label prescribing of drugs, various untrialed medical devices etc. Why was Dr Devathasan singled out?

b] What would constitute a 'proven' therapy? How many trials and what quality of trials are needed?

c] What do we do about Tradition and Complementary Medicine practitioners who are free to make outlandish claims and offer a host of unproven therapies..... some of which may be actually 'endorsed' by the Minister of Health. So if TCM practitioners are championed because they offer unproven options which 'complement' proven western remedies, why is it wrong for Dr Devathasan to do so?

I am all in favour of a greater level of scrutiny of how doctors behave, but SMC need to show it has a rational system in place, and not just engage in random cherry picking of cases to prosecute.

Stem-Cell challenge for the Singapore Medical Council

I was offline for a while for various reasons, and came back today to this curious flurry of reports in My Paper (1, 2 , 3 & 4) about the use of 'stem cells' for the treatment of aging and heart failure (many thanks to Ms Dawn Tay!!). The reports refer to two clinics, one in Parkway's Mt Elizabeth (TheraVitae), and the other in Paragon Medical Centre (Clinique Suisse). Clinique Suisse's Dr YM Wong, incidentally was also featured in a previous blog-post about another whacko scheme.

I must admit I don't know too much about these fancy therapies but a number of bizarre and confused things pop up in the reports:

a] The inconsistent picture of whether these were offered as part of a clinical trial. Both Dr Wong himself and Dr Eugene Sim of Parkway, offerred that these were not part of clinical trials, yet Dr Sim said that these were approved by the Parkway ethics board and the HSA (which would only happen if they were formal trials).

b] These therapies are 'unproven' and are not currently acceptable methods of treatment. Dr YM Wong was quoted as saying:
"We don't talk about clinical trials. We're not reducing people to digits and statistics. We treat people as a whole. I don't think like most doctors do. I'm different. Singapore doctors don't believe that stem cells can be used to delay ageing. They're very conservative and feel that stem cells should be used only in leukaemia and other incurable diseases."

c] Most importantly, the offering of unproven therapies is strictly deemed unethical. Para 4.1.4 of the SMC Ethical Code and Ethical Guidelines state very explicitly: "A doctor shall treat patients according to generally accepted methods and use only licensed drugs for appropriate indications. A doctor shall not offer to patients, management plans or remedies that are not generally accepted by the profession, except in the context of a formal and approved clinical trial."

MOH and HSA was quick to point out that doctors who flout these guidelines are liable for disciplinary action. (The SMC was however, strangely silent.)

But what was really disturbing was that this was going on for about 10 years.

So here is what I believe is an important and very timely challenge for the Singapore Medical Council, especially in the wake of recent discussions about her ability to 'self-regulate'. Did she know about the offering of unaccepted therapies? Or did she conveniently blind herself to the violations and clung obstinately to the mantra that she cannot act unless someone complained officially?

Time for a serious re-boot of the system?

The murky world of drug trials in Singapore

I don't particularly like Strait's Times' Andy Ho's writing. They often tend to be over-jargonized, pretentious and generally confusing.

But this Saturday under the Daedalus column, he touched on a topic that has been somewhat troubling to me, that of the conduct of clinical trials by mega pharma companies.

Drug companies claim that the cost of developing a new drug ranges anywhere between US$0.5 -2 billion. (Other people have suggested that this is grossly inflated and that perhaps only about a fraction of 10% of this is actually spent on FDA required activities.) Although the patent life of a drug is 20 years, about half of this is taken up by research activities before licensing of the drug, hence most new drugs entering the market have only about 7-12 years of effective patent life during which to recover the cost of drug development.

There is therefore a mad rush by mega pharma companies to get their products to the FDA finish line. Not many make it. Last year (2008) only 24 made it through. To regulate this R&D process and to make sure that there is global acceptance of the data generated by these rushing mega pharma companies, the clinical trials are 'regulated' by a series of harmonized dos and don'ts called the Good Clinical Practice (GCP) guidelines. There is a global set that has been harmonized by the International Conference on Harmonization (ICH). Singapore has a set that had is based heavily on the ICH-GCP document.

These guideline do give some comfort that the human experimentation that occurs as a result of the need to do clinical trials is to a large extent highly regulated. Even in Singapore. In Singapore, the Health Product's Act covers all such activities and the Health Science Authorities is the delegated authoritiy that approves the conduct of all clincal drug trials. Every investigator that is involved in clinical trials need to be trained in GCP. Every institution/hospital involved in clinical trials needs to have an instituional review board (IRB) which will provide the ethical review for all protocols.

All this looks very nice and comforting. As usual in Singapore, when we want to tell the world we are 'world class' we make sure that we have all the bases covered. At least on paper, lah....

Let me tell you what I have been concerned about... (and I hope the Ministry of Health are listening here)

a] Despite the existence of IRBs in all the restructured hospitals, not all the IRBs function at the same level of professionalism and competence. This gets worse outside of the restructured hospitals. There is no mandated 'training' or certification of IRB members so we do not know how competent or committed IRB members are in reviewing the clinical trial protocols. Most are just 'arrowed' to do the work, without any proper recognition of work done. To make matters worse, none of the IRBs are ever audited to make sure the processes are as intact as people assume they are.

b] Investigators(consultants,professors etc) are supposed to undergo training and be competent in GCP. But the only institutional expectation at both SingHealth and NHG clusters are only for them to be certified through a nominal online certification programme run by the Collaborative Institutional Training Initiative (CITI) (this one, anybody can pass...!!).

c] The IRBs never ever audit the clinical trials done in the hospital unless some shit hits the fan.

d] The HSA never ever audits any institution to see if they have the processes in place, and if they are actually compliant with whatever they say they are doing. I think basically HSA would rather not know.

e] The clinical trial units that do human experimentation are never audited, and there is no mandated certification of the facilities, so we can only assume that these units can handle emergencies and and manage the subjects if anything goes awry.

So do I have much faith in the environment that has been set up in Singapore so that we can play in the big league? Sadly, no. That we have not had a major incident here is probably more due to good fortune, than any good organization.

So do the investigators do what they say they are doing? Who knows? Does anyone really know what is happening? I have my doubts.