Bias against transplantation policies in China among western bioethicists

During the past few years there have been relentless attacks by prominent, primarily Western bioethicists, against China’s transplantation policies. The central claim is extreme: Thousands of prisoners of conscience have been killed for their organs. For example, Wendy Rogers, professor of bioethics at Macquarie University in Australia, recently claimed that “Chinese prisoners of conscience, mainly Falun Gong practitioners, Uyghurs, house Christians and Tibetans, are murdered for their organs … <creating> a living organ bank where foreign patients and wealthy Chinese citizens can be matched to potential donors, who are then killed on demand so that their organs can be transplanted”. In a co-authored article, Arthur Caplan, professor of bioethics at New York University, and others claimed that “since 2006, mounting evidence suggests that prisoners of conscience are killed for their organs in China with the brutally persecuted Buddhist practice, Falun Gong, among others, being the primary target.”

These criticisms of China are published in academic bioethics journals by well-known scholars without any acknowledgment that reputable individuals and organizations have repeatedly concluded that there is no credible evidence for these claims. This has, unfortunately, led to the establishment of a very biased view on transplantation policies in China among western bioethicists.

Most of what is presented in support of the claims made in the bioethics literature originate from Falun Gong members. Many in the west think that Falun Gong is simply a religious practice emphasizing meditation and self-improvement, but that is not how it is viewed by those who have studied the movement. It was started in China by Li Hongzhi in the early 1990s. It is variously described as a religion, a spiritual practice or a cult. It is well documented that its founder has propagated a high number of fringe ideas and what are generally believed to be objectionable moral ideals. These include such the views that human civilization is being invaded by aliens with the aim of destroying it, that disease can be cured by spiritual practices, and that mixed race marriages are evil. Many of its followers downplay these ideas and it is not clear whether this is for strategic reasons or that they genuinely believe that these are not central to the movement’s beliefs. Falun Gong runs a number of news outlets, such as the Epoch Times, also with a German version. The German Epochtimes has at least at times spread rumors associated with right wing propaganda against immigrant groups. In spite of these shady associations Falun Gong has been spectacularly successful at capturing the support of liberal and progressive groups in the west, also among academics, who regard Falun Gong members as suffering persecution in China because of genuine religious beliefs. It helps, of course, that its followers see themselves as staunch enemies of China’s Communist Party which is particularly useful if one wants to create a positive image among politicians and the public in the US.

The Chinese government has cracked down on the activities of the group in China, because of an understandable fear, based on a number of such episodes in the past couple of hundred years, that a mass movement such as Falun Gong can cause severe social instability. This has led to imprisonment of a high number of Falun Gong followers, based on laws against “disturbing public order”. While it may be legitimate to criticize such punitive measures as over-reactions by the government, it would be wrong to claim that such actions by the government are interference in “religious freedom”.  Falun Gong is similar to western movements such as Scientology which has also been seen as non-religious by authorities in for example Germany. Or one may mention examples of the restrictions by Western and other governments on certain muslim groups that also claim to be religious, justified with reference to the need to national security. Interestingly enough the Falun Gong movement was at first to a certain extent supported by the Chinese authorities as a way to encourage local spiritual practices as opposed to practices originating from outside of China. Once it became clear that the group was anti-science and in particular propagated fringe ideas about medical treatment, the authorities cracked down on the practice. This led to widespread protests among the followers, and then to the subsequent arrests in order to limit its influence. The authorities have been successful in limiting its influence in China. The attention the group has received outside of China as a persecuted religious group by communist China, and as victim of organ harvesting, has greatly enhanced their standing in the west.

The claim about organ harvesting got the attention of politicians and news outlets after a report published by David Kilgour (former member of the Canadian Parliament) and David Matas (a human rights lawyer) in 2006. Ethan Gutman, a journalist, made similar claims a bit later, and they jointly published an updated report in 2016. In these reports, they present evidence that they think proves that there has been, and continues to be, widespread killing of Falun Gong members for their organs in China.

There is no disagreement, and the Chinese government has confirmed this, that the main source or organs in China until at least 2010 was from executed prisoners. There is also no disagreement that unacceptable practices have occurred in China, such as illegal trade in organs and unacceptable transplant procedures in general. There is also no disagreement that some of these practices continue today. In fact, the government of China has attempted to crack down on low quality transplant centers and organ trafficking , and have sanctioned and punished both institutions and individuals for violating China’s transplantation laws and regulations. The controversial claim is that a high number of Falun Gong practitioners, with a “best estimate” of 65000 in about a decade starting in 2000, have been kept in prisons and killed on demand for their organs. According to these critics there are several pieces of evidence for this claim, some of which are:

·       Interviews with detainees, security personnel and others

·       Phone calls to institutions pretending to be persons who seek an organ for transplantation and asking whether a “Falun Gong organ” is available, with what is claimed to be affirmative answers

·       Short wait times for organs with a matched organ being available a short time after a request has been made

·       A mismatch between the number of transplanted organs and the number of judicial executions

All of this is at best circumstantial evidence. The interview and phone call evidence are also clearly biased and open to other, more plausible explanations. The short wait time is evidence for the use of organs from executed prisoners in general, which has not been denied by Chinese authorities. This leaves only the evidence that the number of transplanted organs in the period between 2000 and 2010 exceed the number of organs available from judicial executions (executions after a due process according to Chinese law). This evidence is also problematic because there are no reliable, generally available, figures for executions nor for the number of transplants in China up until around 2010. All of the claims made on the basis of these numbers are therefore to a large degree speculative. Although a number of parliamentary declarations affirming the claims have been adopted both in North-America and Europe, it is significant that independent attempts to corroborate the evidence by official groups have failed. For example, the NewZealand Foreign Affairs, Defence and Trade Committee concluded in 2011

The New Zealand Government investigated allegations made by Falun Gong of illegal organ harvesting from Falun Gong practitioners after they surfaced in March 2006 in a report written by Canadians David Kilgour and David Matas, and publicised through the Falun Gong publication Epoch Times. Neither committee members nor the Government are aware of any independent evidence verifying the Falun Gong claims on organ harvesting. This conclusion is based on both New Zealand and foreign inquiries. New Zealand officials discussed the allegations with Kilgour and Matas; the office of the United Nations Special Rapporteur on torture; human rights non-governmental organisations; and other countries interested in the human rights situation in China. Other international organisations also attempted to verify whether the claims on organ harvesting made in the Kilgour/Matas report had substance. This included a significant US State Department investigation that concluded that there was no evidence of the practice. Officials are not aware of any independent assessment that supports the Falun Gong’s claims of forced organ harvesting

Independent of what may or may not have happened in the early 2000s, there is agreement that there have been substantial reforms in China, both in terms of the number of executions and the system of organ procurement and transplantation, that began in the late 2000s. Beginning in 2005 all death sentences needed to be reviewed by the Supreme People’s Court, resulting in a gradual, but steady and significant, decline in the number of executions.  In 2007 a new regulation on Human Organ Transplantation was enacted, and in 2010 “organ trafficking” was made a crime. A nationwide organ donation program was introduced nationwide in 2013 with the Provisions on Human Organ Procurement and Allocation coming into force. In 2015 the chair of China’s National Organ Donation and Transplantation Committee, and a driving force between the reform program that began in 2005, announced that organs for executed prisoners should no longer be used. As a result of these developments registration and quality controls of donation and transplantation programs have improved dramatically in China, and there has been a crackdown on unacceptable practices such as black market sale of organs and transplant tourism. Given the size of the country nobody can claim that unacceptable practices do not still occur, as they do in many other countries, also in the west.

Independent outside observers who are familiar with the situation in China all confirm that there is now in place a transparent organ procurement and distribution program in the country, and that there is no government sanctioned black market in organs. This includes representatives from the World Health Organization and prominent transplant surgeons from theUS with extensive experience in China. A major piece recently published in the Washington Post also confirmed that the policy change in China has been successful. In spite of this, the critics continue to claim that the practice of killing Falun Gong followers for their organs continues in China (as is evident in the present tense in the quotations above). No new evidence is presented. One major piece of evidence presented in the Washington Post piece is that there is a close match between the official transplant numbers and the sale of immunosuppression drugs used by patients who have received organs. This has been contested by the critics, but the Washington Post has in their reply maintained the accuracy of their original claim.

Not only do the prominent bioethicists make the outlandish claim that thousands of people in China are being killed for their organs based on little or no credible evidence, there have also been attempts to censor articles written by Chinese bioethicists about issues related to transplantation.

When a short piece announcing the new policy ending use of death row prisoners as a source of transplanted organs was published in the Journal of Medical Ethics in 2016, professor Rogers and coauthors demanded a retraction of the article because of what they claimed were misleading statements about the situation in China. The journal did not accept the demand for a retraction, but instead required that the authors post a “correction” to their original piece, at the same time they allowed a “rebuttal” by the criticizing authors. The main correction required was a change from the claim that China had introduced a “law” to prohibit death row organ donation to “a guideline”. This labeling issue is completely beside the point, because it is difficult to translate exactly what the status of a particular piece of Chinese government action is using appropriate English terms for the corresponding Chinese ones. The piece by Rogers and co-workers merely repeated the same exaggerated and unsubstantiated claims made earlier.

When other authors tried to publish a paper in 2014 on attitudes towards cadaveric organ donation among medical and non-medical students in China, the journal, Transplantation, received a letter to the editor criticizing the article for failing to take into account the political situation of organ donation in China, presumably meaning failing to take into account what the authors of the letter think are unethical transplantation practices. There is no particular reason why the authors of a paper reporting the results of an empirical study of attitudes towards cadaveric organ donation should also discuss the issue of use of organs from death row prisoners. The authors refused to have their paper published alongside such a letter to the editor, and therefore decided to retract the paper. Although the critical letter has not been published it is fair to assume that it repeated the same unsubstantiated claims made earlier. The decision by Zhang et al is therefore perfectly understandable, but it is sad to observe the power of a small group of individuals to set the agenda for the debate in the journal literature.

Given the current climate of anti-China sentiment in the West there is little hope that we will see a more balanced reporting of what happens in China. One can still hope, though, that at least some Bioethics journals are willing to consider articles that present a more balanced description of current developments in China.

Justification for no intervention controls in the cervical cancer screening trials in India

The crucial point of disagreement is whether the placebo trials were really necessary to answer the policy relevant question: Could equivalence trials answer give policy makers the answers that they need? The Indian researchers, their funders, and WHO have clearly endorsed the randomized controlled trials with no screening in the control group. The critics disagree. What are the arguments?

Those who defend the trials claim that a local standard of care is necessary because that is to only way to obtain scientifically valid results. The critics, including Ruth Macklin, argue that all arms in a trial should get some form of cervical cancer screening. Again, it is Macklin who provides the argument. It is worth quoting at length from professor Macklin’s paper where she spells out this argument in detail:

It is simply not true that “only a ‘no care’ control arm can give definitive results.” Although the randomised controlled trial is the “gold standard” in clinical research methodology, this does not mean that the control arm must be a placebo. In settings in which the standard diagnostic method is a proven intervention and researchers want to test a new method, or even a less expensive method, it would be unethical to withhold the proven diagnostic method from the participants. The research design would then be a non-inferiority trial, which would test the experimental procedure against the proven intervention to see whether the former is as good (or almost as good) as the latter. That is a perfectly acceptable research design, although it would involve more research subjects and take longer than a placebo-controlled trial. The idea that it is ethically acceptable to design a study in resource-poor settings in which the participants do not have access to a proven diagnostic method outside the trial is flawed. If researchers in India wanted to study VIA to determine whether it is as good (or almost as good) as the Pap smear, they could do so in a tertiary care setting which has the equipment and trained personnel to allow for the routine use of the cytology-based screening method. Using the existing baseline data on the incidence of cervical cancer in India, the efficacy of the experimental method (VIA) could then be ascertained [My emphasis]

It is certainly true that a non-inferiority trial can be designed to establish that a new intervention is or is not equivalent or non-inferior to an existing intervention. The question is whether this design is appropriate in this case for the purpose of answering the question policy makers have. This depends on how we can interpret the results of such a trial. Let us proceed separately with the two possible scenarios, first that the trial establishes that the two interventions are equivalent, and second that they are not.

If the trial establishes that the two interventions are equivalent, we cannot from that fact alone conclude that the new intervention is generally effective due to a problem that Susan Ellenberg and Bob Temple  have identified as lack of assay-sensitivity. This is the ability of a test (clinical trial) to identify an effect reliably. If an equivalence trial demonstrates that two interventions have a similar effect, we can only conclude that the new intervention is actually effective if it is known that the control intervention is effective. In the case of cervical screening trials the only intervention that was identified as effective was systematic screening every three years for at least a decade. An equivalence trial would have to include this intervention as a control if we want the trial to establish equivalence to a known effective intervention. The active intervention arm, however, would likely only include a single screening visit, as this is the feasible policy option to be tested. But it is highly unlikely that any trial would establish the equivalence between this intervention and the worldwide best standard of care. A trial that aims to establish equivalence would therefore be a complete waste of resources. The only sensible aim and outcome is therefore a trial that establishes that the new intervention is inferior to the established intervention.

If the trial establishes that the two interventions are not equivalent, i.e. that the difference between the standard intervention and new intervention is greater than what has been identified as clinically significant, we can indeed conclude that the new intervention is inferior to the established intervention. But that does not mean that we automatically should reject the new intervention as unsuitable in a low income setting: even though it is inferior to the best current intervention. Policy makers in resource poor settings need to know how much better the new intervention is to what is available locally now. If the trial had included an arm with the local intervention, the trial data would allow us to say something about that. In the absence of such an arm in the equivalence trial, we have to use, as Macklin points out, “existing baseline data” as a comparator, and make the assumption that these data are the same as we would have found had we included a control arm in the population under study. This study would basically then have the status of a regular historical control study, and we have seen in the previous post that such data were not sufficient to establish the effectiveness of VIA. 

An equivalence trial will therefore simply not provide the knowledge that policy makers want. They do not want to know how VIA done under ideal conditions compare with PAP smear screening, i.e. done every three year with access to high quality labs. Nor do they want to know how VIA done under field conditions compares with PAP smears done under field conditions. PAP smears done under these conditions may be ineffective: establishing that PAP smear is equivalent to VIA does not establish the effectiveness of VIA. Macklin’s proposal will simply not provide us with any useful results. What we do want to know is how effective VIA is done in field conditions, with testing once or only a few times, not regularly every three years. The reason for this is directly linked to the two problems pointed out with regard to equivalence trials: the effect of VIA varies enormously with regard to how it is carried out, and the relevant comparison is not how VIA done under ideal conditions compares with PAP smears under ideal conditions, but how effective a feasible VIA screening program compares with the current situation of no screening. If that is what we want to know, then we have to have a no-intervention control.

An examination of the results of the three trials supports this analysis. The first trial was published in 2007. It demonstrated that a single VIA screening caused a 35% reduction in deaths from cervical cancer. This is a significant reduction, especially because of the simplicity of the intervention. Had they used any PAP smear intervention in the control arm, it is likely that the results would be uninterpretable. Use of a single PAP smear might have shown no difference between PAP smears and VIA, or that PAP smear screening was inferior.  Since very little is known about the effectiveness of a single PAP smear, the trial results provide no useful policy advice. The results of the second reported trial confirm this analysis. This trial had four arms, one with PAP smears, one with VIA, one with HPV testing and one control. It only found that HPV testing was effective in reducing cancer. Both PAP and VIA were not effective compared with the control group. Had the trial not included a control group we would have correctly concluded that HPV testing is more effective than PAP and VIA, in line with the argument presented by Macklin for an equivalence trial. But we would also have concluded that VIA is effective, because it is assumed that PAP is effective, and there was no difference between them. It turns out, nor surprisingly, that two screening method used in this trial, using PAP and VIA, is not effective at all, even though, under ideal conditions they might be.

In 2009, then, there are results of two trials, one showing that a single screening is effective, one showing that it is not. It is not clear why there is this difference between the two trials. But it does show that how VIA is implemented is crucial for its effect, including any follow up treatment on the basis of a positive result. To repeat the obvious, one simply cannot rely on data from outside a particular trial to infer what the results would be for the trial subjects had one used a particular intervention, or no intervention.

The results of the final and third trial was published in 2014. It was the publication of these results that prompted the last round of criticism in the Indian Journal of Medical Ethics. It demonstrated that screening four times with VIA reduced cancer mortality by 30%, showing that a relatively simple intervention, but still less than PAP smears every three years, could have a dramatic effect on cervical cancer mortality. This is a result that simply could not have been know without the results from this trial, and without a control group with no intervention.

Perhaps what is most damaging for the critics is that any alternative design would also expose a significant number of women to known inferior screening programs, without yielding any useful results. No research design avoids exposing women to known inferior interventions, but only a placebo control trial can provide knowledge useful for policy. Having a state of the art control group in the three trials discussed here would have exposed all the other women in the trial to what is known to be an inferior screening program. Having a truncated Pap smear screening program in the control group would expose all women to known inferior treatments. 

Therefore, even if we agree that these trials provided results that are essential for policy, it does not follow directly from this that the trials were justified. We also have to argue that we are not exposing the individuals in the trial to unjustified risk. Even those who advocate equivalence trials have to do this, since they also expose individuals to known inferior interventions. What alternatives are there in 1998? There is no national screening program. Only the wealthy and educated in India have access to cervical screening programs. There are no plans to introduce any national screening program, and there is agreement that the known, effective screening program, Pap-smears, is unimplementable in the foreseeable future. In fact, 20 years later there is still no national screening program in India. In 1998 there was agreement that more research is necessary to identify a suitable screening program. 

The challenge for the critics is that any research design will expose a large group of people to a known inferior screening program.  And if the design of these trials is not able to answer the policy question, then the critics are exposing all these women to an inferior intervention for no good reason whatsoever. The only way to avoid exposing women to known inferior interventions is to do no research at all. But that would mean that no women get access to something that may be of benefit to them. Doing the research will at least save some lives, even in the control group because of the increased monitoring of this group, and useful knowledge is generated that may be used to benefit future women. Finally, even with a no intervention control group, no woman in the control group is denied any treatment that they would be able to get outside of the clinical trial.

Let me conclude this examination of the ethics of the cervical cancer screening trials by making a few remarks. Most people intuitively object to having no intervention in a control group when there is an effective intervention available, even somewhere else. In an ideal world everyone should have access to useful interventions. However, it should also matter morally whether a given scientific design actually produces useful results, and whether alternative designs allow us to avoid the moral challenge of providing everyone with known effective interventions. The role of bioethicists should be to examine carefully the arguments provided by those who argue in favor of having a no intervention control arm. It is simply not acceptable to simple refer to the Helsinki Declaration, and think that this settles the question of the suitability of alternative scientific designs, in the way that writers in the Indian Journal of Medical Ethics and the Ethics Dumping project tend to do. Once it is clear what the scientific issues are, it is still necessary to weigh the harms and benefits of alternative courses of actions, and then reach a conclusion about how to proceed. But simply claiming that it was already known in 2000 that VIA was an effective screening method, or that equivalence trials can answer the relevant policy questions, do not change the empirical facts that are needed to make morally sound judgments.

Justification for the cervical cancer screening trials in India

What did policy makers need to know in the 1990s?

In the 1990s the established screening method for cervical cancer in developed countries was regular Pap smears. This method is not particularly sensitive, i.e. it misses a relatively high number of potential cancers. The Pap smears therefore need to be done at regular intervals, such as every two or three years. This method also requires highly specialized labs, and highly skilled personnel to interpret the microscopic images. Finally, the women need to come back again to get the results and to get treatment if necessary. If the screening program is carried out with appropriate facilities and personnel, and women come in for regular screening every two to three years between the ages of 20 to 60, the program is effective. Women in India who would follow the recommended procedures, and had access to high quality labs, would have access to an effective diagnostic tool. But there was, and still is, near consensus among experts that at the current stage of development of India, both in general and in its health system, it would not be appropriate to introduce regular Pap smears as a general population based screening program.

In the 1990s researchers were trying to identify a simpler screening tool, that requires fewer visits to clinics, less sophisticated clinics, and personnel that can get the necessary skills with less extensive training.  One such method is visual inspection after application of acetic acid (VIA). This requires less infrastructure both in terms of labs and personnel, and the screening and treatment (cryotherapy) can be done in one visit. Around 2000 VIA was seen as a promising method in low-income settings, but there were worries about its low specificity: it would lead to overdiagnosis and therefore unnecessary treatments. That is, doing VIA once was better at detecting cancers than Pap smears, but less specific, underscoring the previous emphasis on the need to do repeated tests conscientiously in order for a Pap smear screening program to be effective.

Policy makers who want to decide on any alternative screening programs, such as VIA, need to know the answers to two questions:

1. Do we know enough about alternative screening programs to recommend population wide implementation in India?
2.  If we do not know enough, what additional knowledge is needed, and how do we go about getting that knowledge? 

Was it already known in 2000 that cheaper screening methods were effective?

Ruth Macklin has attempted to provide arguments that address the two questions. Her first claim is that it was already known around 2000 that VIA was effective. Therefore, any clinical trial that investigated the effectiveness of VIA was unnecessary, and therefore unethical. Policy makers already know enough to implement VIA as a population based screening method. Her main argument to back up her claim is a report published by WHO in 2002:

The efficacy of VIA was already well established. According to a World Health Organisation (WHO) consultation report in 2002, “The test performance of VIA suggests that it has similar sensitivity to that of cervical cytology in detecting CIN, but has lower specificity. Further research is required to improve its specificity without compromising sensitivity” (2). The WHO report also pointed out the need for training personnel in the use of the method, as well as that for developing standard procedures for quality control. Also needed at the time was research on the development of a simple scoring system to objectively report the results of VIA. However, the important point is that the efficacy of VIA as a screening method had already been established when these trials were conducted in India.[My emphasis]

The problem is that Macklin seriously misrepresents what the WHO report actually says. Here is a statement that Macklin has decided not to refer to:

Information on test characteristics alone does not suffice for making decisions regarding whether VIA may be adapted for use in population-based organized screening programmes in routine public health practice. Evidence on its comparative efficacy and cost-effectiveness versus cytology screening in reducing incidence and/or mortality, as well as information on short-term and long-term consequences arising from decisions taken based on screening test outcomes, is essential for recommendations leading to public health policies. Such evidence may ideally be generated from randomized controlled trials.

According to Macklin, and against WHO, the only type of trial that what was needed at that time was either an implementation trial or a demonstration project. For Macklin, implementation research is

A study design that compares cancer rates following the introduction of VIA in urban wards or rural primary health centres with the past rates of cancer among women who used the same health facilities before VIA was introduced [and it] could provide results demonstrating that the implementation of the new technique was successful

Macklin gives an example of a demonstration project in several African countries where a screening program using VIA and cryotherapy was introduced. Quoting from the report from the project, Macklin goes on to say that

This demonstration project has shown that the ‘screen and treat’ approach can be introduced into existing reproductive health services in low-resource countries. Screening for precancerous lesions using VIA and treatment with cryotherapy is acceptable and feasible at low level health facilities in six African countries

The problem is again that Macklin seriously misinterprets the results of this demonstration project. Fewer than 10% of eligible women in the areas targeted were actually screened. Of the around 1000 who were scheduled for cryotherapy 600 were lost to follow up. Of the 326 women who were identified as having serious lesions requiring treatment, only 96 were followed up. The demonstration project showed that one could implement a screening program, but not a very successful one. The problems in the project were precisely those raised in a 2002 WHO report: There was no evidence that VIA could identify cancer cases reliably in a population wide screening program, because one does not know if such a program will achieve high enough follow up rates of the screened women, and therefore does not know if the program will achieve its goal, reducing the number of cervical cancer cases in the screened population.

As is evident in the WHO recommendations published in 2002 there was general agreement that the evidence was NOT sufficient for implementation of a policy of nationwide screening in a country such as India, and existing mentioned above confirms that. Contrary to what Macklin claim, the 2002 actually endorses the three Indian trials as necessary to obtain knowledge for policy, in addition to, and not instead of, demonstration projects. Here is the full quotation:

Currently, there are three large randomized trials ongoing in India (Dindigul district, Tamil Nadu; Mumbai (Bombay) city and Osmanabad district, Maharashtra) that are addressing the efficacy of VIA screening in reducing the incidence of and mortality from cervical cancer. The programme in Osmanabad district addresses the comparative efficacy of conventional cytology, VIA and HPV testing. The programmes in Dindigul district and Mumbai address the efficacy of VIA in reducing the incidence of cervical cancer. A three-arm, prospective randomized intervention trial in South Africa is currently addressing the comparative safety, acceptability and efficacy of screening women with VIA and HPV DNA testing. This trial is also investigating the effects of immediately treating women who screen positive with cryotherapy, performed by nurses in a primary health care setting. Outcome measures include reduction of high-grade cervical cancer precursors in treated versus untreated women, followed over a 12-month period. A large demonstration project of VIA, which is ongoing in the San Martin region of Peru, aims to investigate the effectiveness and acceptability of VIA integrated with the health services. Those screening positive by VIA are referred for magnified visual inspection after application of acetic acid (VIAM) and immediate biopsy and cryotherapy are provided if indicated by VIAM. A similar intervention involving VIA and VIAM has been initiated in Western Kenya. These studies are likely to provide the required evidence on the longitudinally-derived sensitivity and the cost-effectiveness of VIA in decreasing cervical cancer incidence and mortality.

It should therefore be abundantly clear that there is not enough evidence in 2000 to implement large scale population based screening methods in low- and middle-income countries such as India. It is only by selective quotations from a key 2002 WHO guidance document that Macklin can make her case.

In my next blog I will examine the second, and more important question of relevance for policy makers: If not enough is known about the value of alternative screening methods, what type of research is needed? Specifically, what should be the control group in a Randomized Clinical Trial?