What rules determines a treatment that a medical quiz would recommend?

With great power comes great responsibility

“It seems that no matter what I do, the quiz recommends the client’s drug as the best possible treatment. The only exception is if I say I’m allergic. Or if I say I am already taking it.” Bill Sourour.

Developers are often one of the last lines of defense against potentially dangerous and unethical practices.

We’re approaching a time where software will drive the vehicle that transports your family to soccer practice. There are already AI programs that help doctors diagnose disease. It’s not hard to imagine them recommending prescription drugs soon, too.

“Nothing that we were doing was illegal. In the end, I understood that the real purpose of the site was to push a particular drug.” Bill Sourour.

The more software continues to take over every aspect of our lives, the more important it will be for us to take a stand and ensure that our ethics are ever-present in our code.” 

Read The code I’m still ashamed of, on medium, Nov 13 2016. Code image by Thibault J.

Social media and technology bringing medical information and drugs at our fingertips

Social forums and networking for patients support

International groups of patients are linking up 24/7 through social media to disseminate knowledge, provide peer support, and offer clinical advice. And all of this is delivered quickly, at the touch of a button.

Is social media saving lives? Or is it spreading poor information and damaging private confidentiality? The rapid rise of patient support groups on social media is putting some fundamental ethical questions into the spotlight.

Information and drugs at our fingertips, The BMJ 354:i4527, 18 August 2016.

Tablet image esthervargasc.

Stephen Armstrong explores the role of social media in patient support and considers the benefits, ethical dilemmas, and confidentiality issues that arise.

Maureen Baker, chair of the Royal College of General Practitioners, acknowledges the huge benefit of such groups but cautions that

“these forums should not be seen as a replacement for proper medical care.”

There is No Doubt that DES was a Massive Medical Mistake

DES Action Australia – DES Daughters and Tall Girls, 60 Minutes, 1999

Video published on 24 September 2016 by DES Action Australia.

Includes interviews of Pat Cody, former President of DES Action USA and Dr Jules Black, Queensland Gyneocologist and sexuality expert, about the silence around the DES issue and the difficulties to push for a much needed Australian DES National Public Education Campaign 10 years after the USA first DES national campaign launched in 2001.

DES and Quest to Manipulate Height
DES DiEthylStilbestrol Resources

Synthetic Hormone Given to Healthy Teenage Girls

DES Action Australia – Tall Girls, Today Tonight, 1998

Video published on 24 September 2016 by DES Action Australia.

DES and Quest to Manipulate Height
DES DiEthylStilbestrol Resources

Hormone Treatment Tested on Healthy Young Girls

DES Action Australia – Tall Girls, SBS Insight, 1997

Video published on 24 September 2016 by DES Action Australia.

DES and Quest to Manipulate Height
DES DiEthylStilbestrol Resources

Medical Science Editors, Publishers, Impact Factors, and Reprint Income

Is much of the clinical research that is published still believable?

Editors under Pressure—Avoiding Conflicts

Editors would like to imagine they are simply gatekeepers who facilitate the interaction between authors who wish to impart information and people who want to read it. In fact, they are subject to a raft of external pressures that interfere with this core task. Coauthors are prone to disputes with each other and with reviewers; rejected authors may protest; readers may be dissatisfied; institutions may react inadequately to editors’ concerns about probity; editorial freedom may be compromised by the demands of the learned society that owns the journal; and a commercial publisher might exert subtle—or unsubtle—pressure to increase profitability. All of these distractions increase the possibility of competing interests corrupting the editorial process.

Influence of the Impact Factor

Editors, Publishers, Impact Factors, and Reprint Income, PLoS Medicine, PMC2964337, Oct 26 2010.

Added to this toxic mixture is the impact factor (IF). Just as many clinicians claim that contacts by pharmaceutical company representatives do not affect their prescribing behaviour, so editors are likely to deny that thoughts of a rising IF might influence their acceptance rates. In their paper published this week in PLoS Medicine, Andreas Lundh and colleagues analysed randomised controlled trials published in six high-impact general medical journals during two time periods a decade apart; they calculated the putative fall in IF that would have occurred had publication been denied to papers that were commercially sponsored.

Unsurprisingly, they found the expected association, since IF depends in turn on recent citation rates, and a body of literature shows that industry-sponsored trials attract more citations than those funded by a nonprofit source. There are reasons: for example, randomised controlled trials and meta-analyses are cited more frequently than clinical studies with less-rigorous design, regardless of funding, and high-impact journals are likely to attract the former. There is “gamesmanship,” with commercial sponsors and publishing companies skilled at obtaining publicity in the mass media, a known stimulant for citations. Only slightly dubious is the habit of commercial companies disseminating papers favourable to their product to individual clinicians at conferences or through sponsorship of review papers—themselves a potent accelerator of IF. More culpable is the fact that studies showing positive outcomes for a drug or device under consideration are more likely to be published than “negative” studies; editors are partly to blame for this but so are commercial sponsors, whose methodologically well-conducted studies with unfavourable results tended not to see the light of day, at least in the pretrial registration era.

Lundh and colleagues do not claim that their findings demonstrate that editors’ judgment on acceptance or rejection is influenced by the paper’s predicted effect on IF. Nonetheless, I have heard editors support a paper at a selection meeting by stating that it is likely to be well cited.

Publishers’ Profits and Sponsored Studies

More intriguingly, the second aim of their study was to investigate the possible financial benefits to publishers of the journals they investigated. Their attempted method was to seek data on income from advertisements, reprints, and industry-supported supplements as a percentage of total income. The editors of the two UK-based journals,BMJ and The Lancet, provided the data. The editors of JAMA and The New England Journal of Medicine (NEJM)declined, as did the publisher of Annals of Internal Medicine. The owners of the latter confirmed the proxy data obtained from the US Internal Revenue Service but the publishers of the former two journals, the American Medical Association and the Massachusetts Medical Society, did not respond.

Again, the authors cannot infer the intentions of their nonrespondent editors. Editors are proud of their independence but independence goes only as far as an owner permits, as we know from the sorry history of dismissed editors of NEJM and the Canadian Medical Association Journal, amongst others.

Journals as Leaders: A Paradox

In many ways, JAMA has led the way in promoting publishing integrity—including its call for independent statistical analysis of submitted industry-sponsored trials and its publication of best practice recommendations for professional medical associations. The authors of the latter paper, who include the journal’s editor-in-chief, state:

“Professional medical associations have a duty to bring to their members the best scientific evidence on the efficacy and suitability of drugs and devices. These efforts must be separate from and not affected by industry promotions.”

It is a paradox that the professional medical association that owns JAMA was less than open and transparent with Lundh and colleagues about potential financial conflicts (such as their income from industry sources) as they expect their authors to be.

Stronger Guidance Needed

The various bodies that advise editors may need to strengthen their guidance. The Council of Science Editors’ White Paper on Promoting Integrity in Scientific Journal Publication includes as a potential conflict for editors “employment by an organisation that would obtain some advantage from a favourable product-related publication.” The International Committee of Medical Journal Editors (ICMJE) states that editors who make the final decisions about manuscripts must have no “personal, professional or financial involvement in any of the issues they might judge.” The Committee on Publication Ethics (COPE) code of conduct for editors requires them to prevent business needs from compromising important intellectual standards. None of these organisations comment on the potential conflicts that might arise when a journal or publisher receives a substantial proportion of its income from reprints (23%, Massachusetts Medical Society; 41%, The Lancet; 53%, American Medical Association).

Journal editors have expended much time and effort in teasing out how to handle authors’ and reviewers’ competing interests. They need now to concentrate on their own and those of their employers, lest we reach the dismal scenario described by Marcia Angell:

“it is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine

Should doctors ever be allowed to modify the human species?

Genome editing: ethical considerations

Nuffield Council on Bioethics report – Genome editing: an ethical review – found materials to perform basic experiments are now available to ‘garage scientists.

“… genetic technology has become so powerful that nations need to decide whether or not doctors should ever be allowed to modify the human species.

While the creation of GM humans is not on the horizon yet, the risks and benefits of modifying a person’s genome – and having those changes pass on to future generations – are so complex that they demand urgent ethical scrutiny, …

Read Experts warn home ‘gene editing’ kits pose risk to society, the guardian, 30 September 2016. Download the ethical review short guide.

Has medical science taken a turn towards darkness?

Perhaps half of the scientific literature may simply be untrue

A lot of what is published is incorrect.”
I’m not allowed to say who made this remark because we were asked to observe Chatham House rules. We were also asked not to take photographs of slides. Those who worked for government agencies pleaded that their comments especially remain unquoted, since the forthcoming UK election meant they were living in “purdah”—a chilling state where severe restrictions on freedom of speech are placed on anyone on the government’s payroll. Why the paranoid concern for secrecy and non-attribution? Because this symposium—on the reproducibility and reliability of biomedical research, held at the Wellcome Trust in London last week—touched on one of the most sensitive issues in science today: the idea that something has gone fundamentally wrong with one of our greatest human creations.

Offline: What is medicine’s 5 sigma?, the lancet, Comment, April 11, 2015.

The case against science is straightforward: much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness. As one participant put it, “poor methods get results”. The Academy of Medical Sciences, Medical Research Council, and Biotechnology and Biological Sciences Research Council have now put their reputational weight behind an investigation into these questionable research practices. The apparent endemicity of bad research behaviour is alarming. In their quest for telling a compelling story, scientists too often sculpt data to fit their preferred theory of the world. Or they retrofit hypotheses to fit their data. Journal editors deserve their fair share of criticism too. We aid and abet the worst behaviours. Our acquiescence to the impact factor fuels an unhealthy competition to win a place in a select few journals. Our love of “significance” pollutes the literature with many a statistical fairy-tale. We reject important confirmations. Journals are not the only miscreants. Universities are in a perpetual struggle for money and talent, endpoints that foster reductive metrics, such as high-impact publication. National assessment procedures, such as the Research Excellence Framework, incentivise bad practices. And individual scientists, including their most senior leaders, do little to alter a research culture that occasionally veers close to misconduct.

Can bad scientific practices be fixed?
Part of the problem is that no-one is incentivised to be right. Instead, scientists are incentivised to be productive and innovative. Would a Hippocratic Oath for science help? Certainly don’t add more layers of research redtape. Instead of changing incentives, perhaps one could remove incentives altogether. Or insist on replicability statements in grant applications and research papers. Or emphasise collaboration, not competition. Or insist on preregistration of protocols. Or reward better pre and post publication peer review. Or improve research training and mentorship. Or implement the recommendations from our Series on increasing research value, published last year. One of the most convincing proposals came from outside the biomedical community. Tony Weidberg is a Professor of Particle Physics at Oxford. Following several high-profi le errors, the particle physics community now invests great effort into intensive checking and rechecking of data prior to publication. By filtering results through independent working groups, physicists are encouraged to criticise. Good criticism is rewarded. The goal is a reliable result, and the incentives for scientists are aligned around this goal. Weidberg worried we set the bar for results in biomedicine far too low. In particle physics, significance is set at 5 sigma—a p value of 3 × 10–7 or 1 in 3·5 million (if the result is not true, this is the probability that the data would have been as extreme as they are). The conclusion of the symposium was that something must be done. Indeed, all seemed to agree that it was within our power to do that something. But as to precisely what to do or how to do it, there were no fi rm answers. Those who have the power to act seem to think somebody else should act first. And every positive action (eg, funding well-powered replications) has a counterargument (science will become less creative). The good news is that science is beginning to take some of its worst failings very seriously. The bad news is that nobody is ready to take the first step to clean up the system.

Richard Horton,
The Lancet, Comment, April 11, 2015.

Women and Health Research

Ethical and Legal Issues of Including Women in Clinical Studies, Volume 1, 1994

Women-and-Health-Research
Appendix C includes a DES case study

In the nineteenth century some scientists argued that women should not be educated because thinking would use energy needed by the uterus for reproduction. The proof? Educated women had a lower birth rate. Today’s researchers can only shake their heads at such reasoning. Yet professional journals and the popular press are increasingly criticizing medical research for ignoring women’s health issues.

Women and Health Research examines the facts behind the public’s perceptions about women participating as subjects in medical research. With the goal of increasing researchers’ awareness of this important topic, the book explores issues related to maintaining justice (in its ethical sense) in clinical studies.

Leading experts present general principles for the ethical conduct of research on women–principles that are especially important in the light of recent changes in federal policy on the inclusion of women in clinical research.

Women and Health Research documents the historical shift from a paternalistic approach by researchers toward women and a disproportionate reliance on certain groups for research to one that emphasizes proper access for women as subjects in clinical studies in order to ensure that women receive the benefits of research.

The book addresses present-day challenges to equity in four areas:

  • Scientific–Do practical aspects of scientific research work at cross-purposes to gender equity? Focusing on drug trials, the authors identify rationales for excluding people from research based on demographics.
  • Social and Ethical–The authors offer compelling discussions on subjectivity in science, the evidence for male bias, and issues related to race and ethnicity, as well as the recruitment, retention, and protection of research participants.
  • Legal–Women and Health Research reviews federal research policies that affect the inclusion of women and evaluates the basis for researchers’ fears about liability, citing court cases. Appendix C includes a DES case study.
  • Risk–The authors focus on risks to reproduction and offspring in clinical drug trials, exploring how risks can be identified for study participants, who should make the assessment of risk and benefit for participation in a clinical study, and how legal implications could be addressed.

This landmark study will be of immediate use to the research community, policymakers, women’s health advocates, attorneys, and individuals.

DES DiEthylStilbestrol Resources

How Pharmaceutical Companies Entice Doctors into Prescribing Expensive Medication

An excerpt from Dissenting Diagnosis, by Arun Gadre and Abhay Shukla, published by Random House India

Written by the doctors and public health advocates Arun Gadre and Abhay Shukla, Dissenting Diagnosis is based on a study conducted at Support for Advocacy and Training to Health Initiatives, a Pune-based non-governmental organisation. During the course of this study, Gadre and Shukla interviewed 78 doctors from across the nation in an effort to confront what they consider is an ongoing crisis of the medical profession: doctors, they write in their introduction to the book, are finding “their traditions of ‘keep patients foremost’ rapidly buried under the ruthless logic of ‘keep profits foremost.’” Gadre and Shukla discussed with these medical professionals issues such as lack of regularisation in the private sector, unlawful and unethical practices routinely followed by doctors, the influence of pharmaceutical companies, the state of medical education, and the possibility of a universal healthcare system.

How Pharmaceutical Companies Entice Doctors into Prescribing Expensive Medication, caravanmagazine, 16 April 2016.

In the following excerpt from the book, interviewees speak to the writers about the hold of the pharmaceutical companies over the medicines prescribed by doctors. They describe how, through offers of gifts and benefits, aggressive marketing and sheer persistence, representatives from pharmaceutical companies routinely entice doctors into prescribing expensive and often unnecessary medicines to their patients. The pharmaceutical companies, one of the doctors said, are “like a pack of wolves.”

“Some of my doctor friends boast to me that they have travelled the world, sponsored by pharmaceutical companies. One was telling me with pride that even their shirts, pants, vests and underwear are given by pharmaceutical companies!” says an ophthalmologist from a medium-sized city.

Dr Suchitra, a general practitioner in Chennai, mentions, “The pharmaceutical companies offered to sponsor me for a conference, but I refused. I usually prescribe generic medicines or cheap, branded medicines. But the interesting thing is that once these pharmaceutical companies realized I don’t prescribe their medicines, they stopped visiting me.”

“I have been practising for thirty years. I have not given any ‘cuts,’” a super-specialist from a metropolis shares. “I did not encourage pharmaceutical companies. I change the medicines prescribed to my patients, prescribing cheaper medicines if expensive medicines have been prescribed. And what a big difference this makes to the patient! Sometimes the cost is reduced as much as Rs 35–40 per tablet! Patients are often unnecessarily prescribed expensive brands of medicines, for years on end, sometimes for life. The hapless patient keeps taking these medicines.

“Once, four medical representatives visited me with their bosses. They tried to convince me that I should not replace their brands, while prescribing cheaper brands to patients. We discussed the matter for an hour and their argument was that their company does a lot of research, on which they spend crores of rupees. That is why their brand is more expensive by Rs 30 per tablet.

“After they had finished their speech, I took Rs 1000 out of my pocket and handed it to one of the bosses. Surprised, he asked me what this was for. I answered: ‘You are doing such good work for humankind. This is my small contribution!’”

“After that I emphatically told them that I would help them, but how could I do this at the patients’ expense without telling the patients? Of course, they had no answer to that.”

A big-city surgeon remarks, “Pharmaceutical companies sponsor conferences where nobody bothers to listen to the lectures. Doctors just go to the stalls, and collect gifts. They enjoy the free drinks. It is a filthy business. What can one say?”

“Medical representatives influence the doctors. One of them offered me a trip to Singapore. I refused and told him that I would go at my own expense, and when I wanted,” said a general practitioner from a big city.

A super-specialist from a metropolitan city also shares, “The medical representatives are really persistent; they don’t leave you alone. Earlier, I would get angry at them. One of them pleaded with me, “Sir, you are the only one left. The other doctors, like you, who would earlier not take gifts, have all gradually succumbed. That’s why I am now meeting you too.” Since then, I don’t get angry with them.

“Recently, a medical representative brought along a diamond necklace as a gift, worth Rs 1 lakh.

“I asked him, ‘What’s this?’

“‘A diamond necklace, sir.’

“‘For whom?’

“‘It’s for your wife.’

“Controlling my temper, I asked him, ‘How do you dare to put a necklace on my wife’s neck?’

“The poor fellow was taken aback. ‘It is you . . . you will put the necklace on your wife’s neck.’

“Giving it back to him, I told him in a calm voice, ‘If that is so, then I will buy it with my own money. That is, if she wants a necklace at all!’

“The poor fellow left with the necklace.”

Dr Sumit Das, a psychiatrist from Kolkata notes, “Pharmaceutical companies exist to do business and make profits. But what about doctors? They too put pressure on pharmaceutical companies, telling them, ‘If I prescribe your medicines, send me on a tour to Europe.’

“In the field of psychiatry, pharmaceutical companies bring out new medications every day. There is no evidence that the new medications are better than the cheaper and effective medications that are already in use. And keep in mind the fact that our patients don’t take these medications for just a few days, but often for months or even longer. Yet these unnecessarily expensive medicines are sold and also prescribed.”

“Pharmaceutical companies could have donated money to our department and our institution by cheque. But instead of doing that, I would repeatedly be offered personal gifts, foreign trips, etc. Those salesmen would tell me openly that they are willing to spend on an individual, not on the institution,’ comments a general surgeon from a metropolitan city.

A paediatrician from a metropolitan city suggests, “The practice of pharma companies sponsoring doctors for conferences and CME (Continuing Medical Education) workshops must be stopped immediately.”

A gynaecologist from a big city observes, “The area manager of a pharmaceutical company once paid me a visit along with his army of representatives. He asked me why I regularly use a certain product manufactured by them.

“I answered, ‘It is cheap, it is effective. That’s why.’

“He was confused. He asked me in bewilderment, ‘Madam, we never give you any gifts.’

“I replied, ‘There is no need for that.’

“He just could not believe it. He kept asking, ‘How can this be, madam? Please tell me the reason.’

“This is the ridiculous situation that prevails. This is the reality.”

A paediatrician from a big city mentions, “Our branch [of a doctors’ association] was functioning well. We would organize CME workshops with our own funds. Gradually, the pharmaceutical companies pushed their way in. From 1995 onwards they began to organize their own CME workshops. Earlier, we would focus on the issues of importance that we had decided upon. But then the pharmaceutical companies began to select only those topics that would help them promote their new drugs. The workshops were free, with liquor thrown in. Finally the doctors in our city decided that all workshops henceforth would be organized by the pharmaceutical companies. I would ask them why they couldn’t spend Rs 1000 per year on their own education. Why do you want it free? Finally, through a secret ballot, my opposition was set aside and the basic principles of our [doctors’ association] branch were changed in favour of the pharma companies. Obviously, I withdrew from it. Now all workshops in our city are conducted by pharmaceutical companies.”

“A rampant malpractice is in the area of prescribing vaccines—it is organized, and takes place on a large-scale in planned fashion. The practitioner gets a cut on the Maximum Retail Price (MRP). The more expensive the vaccine, the higher the cut. The cut is even more than the consultation fee. The doctor gets both—the cut from the company and the fee from the patient,” notes Dr Vandana Prasad, a paediatrician from Delhi.

“The pharmaceutical companies are like a pack of wolves. They keep pestering you and encourage you to accept some incentives. Once you take anything from them, they immediately become arrogant. Now they begin to ask you directly, ‘Why don’t you prescribe our medicine?’ They start dictating terms, and because you have accepted money and gifts, you are morally bound to them,” Dr Sanjay Bhatnagar, a paediatrician from Delhi, also shares.

A surgeon from a megacity mentions, “The government cannot provide funds, and if the pharmaceutical companies therefore sponsor conferences in a transparent manner, there is nothing wrong with it. The MCI wanted to do something about this.”

A skin specialist from a big city says, “The pharmaceutical companies have created mayhem. Things like conference sponsorship by drug companies must be stopped. The MCI is aware of the problem, but there are lots of loopholes that can be exploited. Nowadays, doctors take money from pharmaceutical companies and prescribe ten to twenty medicines in a single prescription. There is always an antioxidant tablet prescribed, whether it serves any purpose or not.”

A skin specialist from Kolkata, Dr Jayant Das also remarks, ‘Now pharmaceutical companies are resorting to a new strategy. “For example, they don’t even produce Doxycycline (an established antibiotic) capsules, which cost less than Re 1 per capsule. Instead, they add a useless component like lactobacillus with Doxycycline, and then sell each of those capsules for Rs 5. And when the ordinary, cheap Doxycycline capsule is not even available in the market by design, one has no choice but to prescribe the expensive medicine. This is happening without any check with respect to many medications. One company recently withdrew a medication available for Rs 2. They made some token changes in the formulation and the same tablet is now sold by them for Rs 15!”

Another skin specialist from a big city observes, “Pharmaceutical companies try to give money to doctors under the pretext of conducting studies on their medicines. Such bogus clinical trials are conducted openly. The doctors lure the patients with the promise that the stated medication has come from abroad, and if you want to have it free, you would have to just sign this form, that’s all! Please sign here. Doctors collect the signatures on the forms. Sometimes they just fill up the details. Once they have given the papers for ten to twelve cases (even without prescribing the medication) they get a cheque from the pharmaceutical company.

“If one puts an end to the money pharmaceutical companies spend on doctors, medicines will definitely become much cheaper. That must be ensured, for the benefit of patients. Doctors should be legally compelled to prescribe only generic medicines.”

A general surgeon from a big city offers, “Take the example of Lactulose, which is used to treat constipation. It costs about Rs 180 for 200 ml, that is, around Rs 900 a litre. This is a by-product of the sugar industry. Actually, this should cost less than sugar, i.e., less than Rs 60 per kg. Elderly people will be taking this for years together. Shouldn’t the prices of such medicines be regulated? No. The loot continues.”