Letters · Correspondance
Support of clinical trials
[See Letter: Bench research versus clinical trials]
David Sackett suggests that the Medical Research Council (MRC) is neglecting clinical trials, a key area of health research [full article].1 In fact, MRC is improving support for clinical trials and correcting some of the problems identified by Sackett.
In fiscal year 1999/2000, MRC's investment in a total of 100 trials is $9.7 million, including 32 trials ($2.0 million) funded through the UniversityIndustry Program. MRC provides $250 000 for trials methodology studies and awards training and career support to trials researchers, such as Michael Kramer of McGill University, an MRC Distinguished Scientist. Industry partner funding, leveraged through the UniversityIndustry Program, provides a further $8.7 million. The total annual investment in MRC-sponsored trials research is therefore in excess of $18.7 million.
MRC's support for trials has more than doubled since 1997/98, while the overall grants budget has increased by 31%. The increase in support of trials is proportionately greater than for any other MRC program. Unfortunately, MRC's budget still cannot support all meritorious applications. Sackett noted that in the last 2 competitions 40% of deserving trial proposals could not be funded; for other grants, the figure was 59%. Financial constraints also force Council to cut budgets of approved grants by usually 10%20%. In the last 2 competitions, Council has spared the budgets of approved trials, recognizing their unique nature.
MRC has launched a program to support international trials (www.mrc.gc.ca/proposals/proposals.html). We sponsored an evaluation of the outcomes of MRC-funded trials and a recent workshop where leading researchers debated the future of trials research, as MRC transforms into the Canadian Institutes of Health Research. The Canadian Institutes of Health Research's commitment "to excel in the creation of new knowledge and its translation into improved health for Canadians" will require substantial investment in clinical trials.
Mark A. Bisby
If the WCB can do it, why not others?
If ever we need evidence of the failure of state-monopoly medicine, it is found in the emergence of special expedited care for injured workers [full article].1 Workers' compensation board (WCB) insurance schemes are founded on a sound accounting principle: Is it worthwhile paying more to get the service now, or should the worker wait (and be compensated by the board) until the public system can deliver the care the worker needs? In many cases workers would remain disabled for life if they waited for the public system to respond.
However, this same accounting principle is not carried over into the health care system the rest of us have to live with. It is hypocritical for politicians to turn a blind eye to this practice. Why should injured workers be able to jump the queue while all other citizens are forbidden from using their disposable income to purchase expedited care?
The call to government must be clear. Either fund the system properly or allow citizens to buy medical care privately, much the same as injured workers are now having their surgery paid for privately. The presence of privately funded WCB schemes will ultimately be the litmus test of inappropriate levels of government funding for medicare in Canada.
Derryck H. Smith
Look beyond the skid-row image
By chance I came across an article in CMAJ by Deborah Jones [full article]1 that misrepresented the Downtown Eastside of Vancouver in such an irresponsible way that I felt obliged to write even though the article was printed some time ago. An article with questionable research that demonizes Vancouver's oldest community and its diverse population of residents, most of whom are law abiding, does not reflect favourably on a medical journal dedicated to healing.
Jones suggests that some 7000 injection drug users live in the Downtown Eastside. This figure is wrong; many drug users come from outside the community to use the needle exchange. The Vancouver Injection Drug Users' Study (VIDUS; cfeweb.hivnet.ubc.ca), involving 1300 injection drug users over 4 years, reported that 68% of them live outside the Downtown Eastside.
Jones also states that the Downtown Eastside has a "fluctuating population of 10 000 to 25 000 people." Most community leaders that I talked to agree that the population is from 10 000 to 12 000 if the single family homes in Strathcona are not counted, and from 15 000 to 16 000 if they are. All community leaders agree that the Downtown Eastside has a stable population base. Even residents who move from hotel room to hotel room often do not move out of the neighbourhood.
To label an entire community as "Skid Road" devalues both the local residents and their neighbourhood. When the only thing the media can see is the skid-row image, they cannot see the caring community that exists behind that negative façade.
The article carries an implied tone of contempt for some of the most ill and powerless people in our society and depicts local residents as losers with no redeeming qualities. Without doubt, contempt is the opposite of attention. One thing many residents have in common is poverty, and they live in that stressful condition with a dignity and caring that gives the neighbourhood surprising strength.
I am sure readers would agree with the Downtown Eastside woman who said, "I need to connect with someone who believes in me and helps me believe in myself."2
Real-world effectiveness of antihypertensive drugs
James Wright and colleagues reported results of a meta-analysis of data on the effects of various antihypertensive drugs [full article].1 Their stated purpose was to assist physicians in choosing an initial antihypertensive drug by systematically quantifying the available evidence on efficacy, defined as lowering blood pressure and preventing adverse outcomes. They did not achieve this goal, however, because they focused exclusively on clinical trial data. Although they mentioned the importance of exercising treatment decisions on the basis of the best available evidence, they failed to remind physicians that the real-world effectiveness of antihypertensive therapies is also largely a function of patient compliance. Unfortunately, although Wright and colleagues included data for study withdrawals, they did not consider that real-world compliance cannot be studied under the conditions imposed by trials.2
If they had deemed results from studies that investigated compliance with antihypertensive therapies in actual practice as additional evidence worthy of consideration, physicians would also have been informed that class-specific patterns of persistence with initial antihypertensive drug therapy have emerged3,4 [full article]5, [full article]6. Persistence with antihypertensive therapy, for example, is generally poor, particularly for initial therapy with older agents such as diuretics and ß-blockers. Therefore, to conclude, as the authors have, that physicians should select a diuretic in the absence of contraindications ignores the best available evidence. If the ultimate goal of antihypertensive therapy is to control hypertension and to avoid cardiovascular events, then physicians must consider all available evidence. An antihypertensive medication is only efficacious if a patient remains on therapy, and initial choice of antihypertensive therapy appears to be a significant factor in achieving this outcome.
J. Jaime Caro
Real-world effectiveness of antihypertensive drugs
[The authors respond:]
We appreciate the letter by Jaime Caro and Krista Payne; however, we disagree with their conclusion. Before doctors consider choosing a drug on the basis of real-world compliance, they should ask 2 questions. Is the evidence suggesting a difference in compliance likely to be true? If there is a difference, what is the magnitude of that difference and is that magnitude likely to lead to a difference in morbidity and mortality? The answer to both questions in this case is No.
With regard to the first question, 2 studies1 [full article]2 suggest that compliance is better with new drug classes than with old drug classes, and 2 studies3,4 suggest that there is no difference in compliance. These 4 studies are observational and are subject to bias (i.e., patients prescribed drugs from different classes are not comparable). The most likely bias in the 2 studies claiming a difference is that patients receiving new drugs were more likely to have been given a drug sample in the doctor's office. Old drugs are not available as samples. This sampling would not be captured in the database and would bias the results in the direction seen. The authors should have been aware of this confounder but did not mention it. Lower compliance with the old drugs, thiazides and ß-blockers, is highly unlikely to be true; a double-blind randomized controlled trial designed to test this hypothesis demonstrated fewer withdrawals with the old drugs than with the new drugs.5
With regard to the second question, in the study by Caro and colleagues2 the largest absolute difference in nonpersistence was between thiazides and angiotensin-converting-enzyme inhibitors: 9% at 6 months and 13% at 4.5 years. Would this small difference in compliance lead to a difference in morbidity and mortality? We believe it is highly unlikely, and randomized controlled trials would be required to answer this question. It is important that doctors not be fooled into thinking that observational studies measuring compliance are a substitute for randomized controlled trials that are designed to be generalizable and to measure clinically important outcomes.
James M. Wright
Why aren't we falling for anticoagulant therapy?
In his editorial regarding the reasons why so many eligible patients with atrial fibrillation are not receiving anticoagulant therapy [full article],1 Stuart Connolly suggests that anticoagulant therapy is contraindicated in elderly patients with a history of falling. A recent study2 demonstrated that for the risks of anticoagulation to outweigh its benefits, the average elderly person must fall approximately 300 times in 1 year; the study concluded that the risk of falling is not an important factor in the decision about whether to offer antithrombotic therapy to elderly people with atrial fibrillation.
Connolly focuses on patient factors involved in the lack of appropriate use of anticoagulants, but physician factors may be just as important. Treatment of patients with warfarin is a time-consuming, poorly remunerated aspect of clinical care, requiring multiple phone calls from the laboratory and contacts with the patient to explain dose adjustments. This may help to explain why physicians seek reasons (including a predisposition to falling) not to offer warfarin therapy to eligible patients. Before this care gap can be closed, both patient and physician factors need to be addressed.
Why aren't we falling for anticoagulant therapy?
[The author responds:]
Malcolm Man-Son-Hing draws attention to 2 interesting factors related to underuse of anticoagulant therapy in patients with atrial fibrillation. Anticoagulant therapy is inconvenient both for physicians and for patients. To my knowledge, there is little information about the factors that influence physician decisions to prescribe (or not prescribe) anticoagulant therapy for atrial fibrillation. Large anticoagulation services are available in many urban centres, and many of these accept referrals from physicians. This reduces the burden of caring for these patients. It would be interesting to know whether anticoagulant therapy is more readily prescribed in such areas. Would the wider availability of such a service increase anticoagulant use in atrial fibrillation?
Man-Son-Hing also draws attention to his recent analysis of the relation between anticoagulant therapy for atrial fibrillation and risk of falling among elderly people. His Markov decision analytic model suggests that the benefitrisk ratio favours using anticoagulant therapy even in elderly patients who are at high risk for falling. The reliability of decision modelling (based on literature review) is only modest. In the absence of randomized trial data pertaining to this issue, I would remain cautious about prescribing anticoagulant therapy in elderly patients with a history of repetitive falling.
Stuart J. Connolly
Fear and loathing of tuition fees
I applaud Brian Cummings for identifying some of the most important issues surrounding resident tuition fees [full article].1 Although I understand that universities are experiencing chronic underfunding, this is no justification for the attempt at a cash grab from the newest members of the medical profession.
What will the universities offer us in exchange for this monetary outlay? Will they pay the interest on our student loans? Can they even guarantee that repayment or interest on those loans will be deferred (given our status as students)? Are they prepared to reimburse us fairly for the teaching that we do?
If more universities succeed in instituting tuition fees for residents, the postgraduate training environment will be changed drastically. The quality of training and the delivery of health care will both be at risk.
Fear and loathing of tuition fees
In the Pulse column in the Sept. 7 issue of CMAJ Lynda Buske provided a thorough comparison of 1998 tuition fees for medical residents across the country [full article].1 I would like to clarify the history behind her statement that "in Quebec, government grants help defray a large portion of the tuition fee."
From the time that resident tuition fees at the 4 medical schools in Quebec (namely Laval, Sherbrooke, Montreal and McGill) increased substantially about 4 years ago, the Fédération des médecins résidents du Québec (FMRQ) has been waging a battle with the universities and the government of Quebec. The universities have been unyielding in their determination to maintain the tuition fees. However, after several years of efforts (including strike days) on the part of the residents, in June 1999 the provincial government agreed to finance a portion of the tuition fees. A new article (article 13.08) was added to the residents' collective agreement: as of 1999/2000 the residents will pay $700 in tuition fees and the balance will be paid by the Ministère de la santé et des services sociaux directly to the universities. The government will also reimburse residents for the same fraction of their 1998/99 fees retrospectively. The collective agreement can be downloaded from www.fmrq.qc.ca/a-index.htm (available in French only).
This was a major victory for medical residents in Quebec. I hope residents in other provinces will achieve similar success in their negotiations.
Non-heart-beating organ donation
We read Graham Campbell and Francis Sutherland's paper on non-heart-beating organ donation [full article]1 with interest. Several aspects of their proposal concerned us.
We feel it is inappropriate for a physician to approach a live patient's substitute decision-maker regarding consent for organ donation. This approach would undermine confidence in the physician's (and institution's) primary commitment to optimizing the interests of the patient.
However, it is not simply the appearance of primary commitment to the patient that is important. Although clinicians caring for brain-injured patients may consider the potential for organ donation before declaration, criteria for brain death are firm. It is therefore straightforward at present for a physician to mentally separate the time for management in accordance with primary concern for the patient from that for potential organ donation. Under the authors' proposal, the assessment of severity of brain damage could be influenced by the prospect of organ donation. The authors retrospectively propose criteria for donation. When defining candidacy in practice, the potential for bias in recommending withdrawal of life support on the basis of irremedial damage would be far greater.
This type of bias might also affect dosage or timing of palliative medication. Under the authors' proposal, transplant physicians would have an interest in rapid deterioration of organ donors, thereby avoiding protracted hypotension and optimizing organ integrity. Over time, this interest might influence others' management of palliation following withdrawal of life support.
Another difficulty would arise in the operating room: Who would pronounce the patient dead? A physician would need to be immediately available to minimize delay in harvesting. However, there would be no reason for an anesthetist or intensivist to be involved at this stage and the harvesting team would have a conflict of interest regarding timing of the pronouncement.
Cameron B. Guest
Non-heart-beating organ donation
[One of the authors responds:]
We agree that potential ethical problems accompany this type of organ donation and they must be addressed before embarking on non-heart-beating organ donation. Cameron Guest and Hugh Devitt feel it is inappropriate for physicians to approach a family regarding organ donation while the patient is still "alive." Clearly, with brain-dead patients and with severely brain-injured patients with no hope of survival, giving the bad news to relatives should not include an immediate request for organ donation: a family needs time to digest the death of a loved one. Indeed, giving the bad news and requesting organ donation at the same time does give the appearance of a conflict of interest. Studies indicate that success in obtaining consent is improved by separating the 2 events.1,2
Deciding to withdraw care in the event of a hopeless situation is different from withdrawing it when brain death is declared, because the criteria are not as well defined. However, in patients with severe brain injury, there is still one more criterion to meet cardiac arrest before death can be declared and organs retrieved. We believe that properly informed families can understand this situation and make a decision.
With a policy for non-heart-beating organ donation in place intensivists might change the way they treat severely brain-damaged patients or change the time that they declare brain damage irremediable, to facilitate organ donation. This is a real problem that would require an oversight committee of arm's-length observers. This committee must assess every case, give timely direction to the physicians involved and review the process once completed.
The criteria for declaration of death in the operating room must not change from the normal hospital practice. The people who normally declare death intensivists, neurosurgeons and neurologists should do so in this circumstance. The transplant team has no role in the declaration of death.
Clearly there are potential ethical pitfalls associated with non-heart-beating organ donation. However, the existence of pitfalls should not prevent us from proceeding with caution. Proper and ongoing review of the process should be sufficient to check any slip down an ethical slope.
An increasing number of Canadians are dying without a lifesaving organ transplant. To ignore a source of organs because of a potential ethical problem creates a real ethical problem.