Committee: Discipline
Decision Date: 06 Mar 2018
Summary:
On March 6, 2018, the Discipline Committee found that Dr. Dr. Abida Sophina Jamal committed an act of professional misconduct, in that she has failed to maintain the standard of practice of the profession, in that she has engaged in an act or omission relevant to the practice of medicine that, having regard to all the circumstances, would reasonably be regarded by members as disgraceful, dishonorable, or unprofessional, and in that she has engaged in conduct unbecoming a physician.
Dr. Jamal is a physician who received her certificate of registration authorizing independent practice from the College of Physicians and Surgeons of Ontario (the “College”) on June 17, 1991. In 2002, she completed her PhD at the University of Toronto in the field of clinical epidemiology of osteoporosis, with specific interest in the use of nitrate drug treatment.
Between 2007 and 2015, Dr. Jamal held an appointment to the Active Staff at Women’s College Hospital (“WCH”) as well as an appointment as a Scientist at WCH’s Research Institute. She was also appointed as an Associate Professor in the Department of Medicine, University of Toronto. In addition to her research activities, she practiced endocrinology at WCH.
Dr. Jamal resigned from WCH in 2015. Up to the hearing date, she continued to practice endocrinology in the community in an office-based setting in Toronto.
Dr. Jamal’s Research in Osteoporosis: three research studies
Dr. Jamal had been involved in the publication of study protocols and research investigations related to the use of nitrate drug treatment in osteoporosis. She conducted three different research studies: the JAMA Study, the Sclerostin Study, and the NABT Study.
The JAMA Study
Dr. Jamal was the Principal Investigator in a study entitled “Effect of Nitroglycerin Ointment on Bone Density and Strength in Postmenopausal Women: A Randomized Trial”. This study was published by Dr. Jamal, Dr. Richard Eastell, MD, University of Sheffield and Dr. Stephen Cummings MD, California Pacific Medical Center Research Institute (“CPMCRI”), among others, in the Journal of the American Medical Association (“JAMA”) on February 23, 2011.
The JAMA Study was a double blind placebo-controlled randomized control trial designed to determine if nitroglycerin increases lumbar spine bone mineral density and to evaluate changes in bone mineral density. The JAMA Study concluded that among postmenopausal women, nitroglycerin ointments modestly increased bone mineral density and decreased bone resportion. The Canadian Institute of Health Research (“CIHR”) funded the JAMA Study in the amount of $536,796.00. It involved the participation of 400 women in the run-in phase and ultimately enrolled 243 postmenopausal women between the ages of 50 and 80.
As Principal Investigator, Dr. Jamal had full access to all of the data in the study and took responsibility for the integrity of and the accuracy of the data analysis.
The Sclerostin Study
Following the publication of the JAMA Study in 2011, a subgroup of subjects were included in a follow-up study conducted by Dr. Jamal and others. Its purpose was to examine the possible role of sclerostin, a negative regulator of bone turnover, as an underlying mechanism for the effects of nitrates on osteoporosis as had been previously reported in the JAMA study.
A manuscript was prepared and submitted to a journal but was rejected. Dr. Jamal was among the co- authors of this study. It concluded that nitroglycerin substantially increases bone mass in postmenopausal women by decreasing sclerostin production.
The NABT Study
On October 25, 2013, Dr. Cummings, in collaboration with Dr. Jamal and others, submitted a planning grant application to the National Institutes of Health entitled “The NO Fracture Planning Grant”. Building on the results of the JAMA Study, Dr. Jamal and her collaborators sought funding for a large scale randomized control trial to test the efficacy and safety of daily nitroglycerin treatment to prevent osteoporotic fractures (the “Fracture Trial”). The results of the JAMA study are quoted in the grant application as part of the rationale for the Fracture Trial. As a preliminary step, Dr. Jamal and others commenced a study to establish the appropriate formulation and dose of nitrate treatment for use in the anticipated Fracture Trial. This study is known as the “Nitrates and Bone Turnover (NABT): trial to select the best nitrate preparation.
The NABT Study was conducted between 2012 and 2014. The study was funded by CIHR in the amount of $263,914, in addition to other sources of funding. The study enrolled 420 women in the run-in phase and ultimately enrolled 210 women aged 50 or older.
Dr. Jamal is identified as the Primary Investigator in the NABT Study Protocol.
Professional Misconduct
On October 9, 2015, WCH concluded an investigation into the three research studies that had been conducted by Dr. Jamal (the JAMA Study, the Sclerostin Study, and the NABT Study). WCH found, and Dr. Jamal admits, that in respect of these studies, and in respect of the WCH investigation, Dr. Jamal engaged in research misconduct including:
-Dr. Jamal intentionally manipulated study data in each of the JAMA Study, the Sclerostin Study and the NABT Study, with the intention of supporting the underlying study hypothesis in each case;
-Dr. Jamal made wholly unjustified and completely inappropriate allegations against her Research Associate;
-Dr. Jamal systematically altered patient records to match previously altered datasets;
-Dr. Jamal deleted relevant evidence after she had knowledge of the investigation;
-Dr. Jamal failed to maintain and properly archive raw data;
-Dr. Jamal failed to make raw data available to collaborators;
-Dr Jamal intentionally represented falsified and/or fabricated data as raw data;
-Dr. Jamal used falsified results from one study to apply, obtain and use funding for the follow-up Sclerostin and NABT studies.
Concerns Regarding the Integrity of Data Arose in the NABT Study
In July 2014, the collaborators in the NABT Study commenced the process of collecting and analyzing data. Serum and urine samples were analyzed by the University of Sheffield (the institution affiliated with Dr. Eastell) and the data derived from the samples was sent to Toronto for statistical analysis. Dr. Jamal’s role was to complete the statistical analysis of the data collected in the NABT Study. While Dr. Jamal was assisted by her Research Associate in data entry tasks, her Research Associate was not trained to analyze data, and it was Dr. Jamal’s sole responsibility to analyze data and run the statistical analysis.
On August 18, 2014, Dr. Jamal’s Research Associate completed the data entry and provided Dr. Jamal with data files to use in her statistical analysis. Between August 20 and 25, 2014, Dr. Jamal generated a statistical analysis that she shared with her collaborators. As was revealed in the subsequent WCH investigation, unbeknownst to her colleagues and collaborators, Dr. Jamal had manipulated the data and falsified these study results.
On September 13, 2014, Dr. Jamal shared the favourable results of the statistical analysis on the NABT Study to a small group at the American Society for Bone Mineral Research (“ASBMR”) Conference in Houston, which included Dr. Jamal’s co-collaborators, Drs. Eastell and Dr. Cummings. Dr. Eastell, however, could not understand the results presented by Dr. Jamal, as one aspect was unexpected and not in keeping with the other results from a biological perspective. He asked Dr. Jamal to provide him with the data she relied on so that he could examine it. In response to his request, Dr. Jamal purported to send the data files that had been created by her Research Associate on the premise that this was the data that she relied on to conduct her statistical analysis.In fact, the WCH’s investigation revealed that the files Dr. Jamal sent were not what her Research Associate had prepared. Rather, Dr. Jamal sent the files that contained the manipulated data she relied on in her statistical analysis, which she created moments before sending them to Dr. Eastell.Had Dr. Jamal sent Dr. Eastell the files prepared by her Research Associate, Dr. Eastell would have immediately seen that the data did not support the results Dr. Jamal had circulated to collaborators and presented at the ASBMR meeting.
Ultimately, Dr. Eastell conducted his own statistical analysis, relying on data directly from the source. In his email to Dr. Jamal and Dr. Cummings he indicated that his results did not support the study hypothesis as they showed no difference between treatment groups compared with the placebo controls, a significant departure from Dr. Jamal’s results.
The Research Associate, concerned with the discrepancy between Dr. Eastell’s results and Dr. Jamal’s, requested that Dr. Jamal send her a copy of the data she had sent to Dr. Eastell so she could re-check her data entry. She was concerned she may have made mistakes in her data entry, and that this may have impacted Dr. Jamal’s analysis. Dr. Jamal purported to do this, but instead sent her Research Associate the data her Research Associate had prepared so that she would not see that Dr. Jamal had sent Dr. Eastell a different set of data. Had she actually provided her Research Associate with what she had provided to Dr. Eastell, her Research Associate may have detected that Dr. Jamal altered the data. The Research Associate reviewed the data and noted that she had made 16 typographical data-entry errors (in a dataset containing over 1000 reported values). The Research Associate corrected these typographical errors and provided a corrected spreadsheet to Dr. Jamal the same day. These typographical errors would not have generated the statistical analysis originally prepared by Dr. Jamal and shared with her collaborators and colleagues.
Dr. Jamal then purported to “re-enter” the data on her own. She generated a new statistical analysis and sent her results to Dr. Eastell and Dr. Cummings without copying her Research Associate. In her email, she represented that she re-entered the data provided from the source (the University of Sheffield) and confirmed her re-analysis was in line with Dr. Eastell’s. She attached a word document with a statistical analysis and pointed to her Research Associate as the source of the discrepancy between her initial analysis and Dr. Eastell’s.
Dr. Eastell continued to try to understand the difference between his analysis, which did not support the study hypothesis, and the one originally conducted by Dr. Jamal, which did support the study hypothesis. He examined the data from various sources including the original data derived from the serum and urine samples at the University of Sheffield and the data subsequently provided to him by Dr. Jamal. Subsequently, in his email to Dr. Cummings and Dr. Jamal he indicated that he was worried the changes could have been made deliberately as he could not think of another explanation.
Dr. Jamal replied to Dr. Eastell indicating that she agreed with him and sought to deflect blame, advising her collaborators that the spread sheet she sent was based on her Research Associate’s data.
On January 14, 2015, following Dr. Eastell’s revelation that deliberate changes had been made to the data, Dr. Jamal, Dr. Cummings and Dr. Eastell participated in a videoconference, focusing on Dr. Jamal’s concern that the Research Associate had changed the data and how Dr. Jamal should approach the matter with her Research Associate.
On January 22, 2015, Dr. Jamal sent Dr. Cummings and Dr. Eastell a draft letter she had prepared to send to all those who had participated in the discussion about the NABT Study results at the ASBMR conference, wherein she acknowledged that the previous data that she had shared was incorrect, that the reanalysis demonstrated no relationship between bone turnover markers and nitrates, and that there had been systematic modifications to the data. In her email, Dr. Jamal advised Dr. Cummings and Dr. Eastell that she had spoken with her VP of Research about the concerns regarding the conduct of her Research Associate. This is untrue. Dr. Jamal mentioned nothing to the VP of Research.
After concerns were raised about the NABT data in late 2014 and early 2015, Dr. Cummings and Dr. Eastell discussed the need to confirm the published JAMA results. It seemed unlikely that the JAMA results would differ so significantly from the NABT results. Given that Dr. Cummings, Dr. Jamal and Dr. Eastell had sought funding for a planning grant for a large scale clinical trial (the NIH NO Planning Grant) based on the JAMA results, Dr. Cummings wanted to confirm the JAMA analysis. Accordingly, he requested that Dr. Jamal provide the raw data. On January 20, 2015, Dr. Jamal wrote to Dr. Cummings and Dr. Eastell claiming she had some “bad news” regarding the data sources for the JAMA paper. She advised that none of original/raw data remained available - it had either been lost or destroyed. On January 27, 2015, Dr. Jamal emailed Dr. Cummings advising that she, in fact, did locate some raw data for the JAMA Study. She attempted to discourage any further investigation into the JAMA data.
University of Toronto Inquiry
On February 25, 2015, the Scientific Director at the institution affiliated with Dr. Cummings, lodged a complaint against Dr. Jamal with the Research Oversight and Compliance Department of the University of Toronto, requesting an investigation into whether the data in the NABT Study had been intentionally manipulated and if so, by whom, and whether the raw data for the JAMA Study exists. The University of Toronto conducted a preliminary inquiry.
Throughout the University of Toronto Inquiry, Dr. Jamal falsely maintained she played no role in the manipulation and fabrication of the study data and continued to deflect blame to her Research Associate seeking to avoid detection. In her submission to the University of Toronto Inquiry, Dr. Jamal purported to include the data sets prepared by her Research Associate. The files she provided to the University of Toronto Inquiry were, in fact, the files Dr. Jamal created shortly before she sent them to Dr. Eastell (and as subsequently determined, reflected the data she had manipulated). Dr. Jamal made this statement to deliberately mislead the Inquiry and to falsely and deliberately implicate her Research Associate. Dr. Jamal asserted falsely during the University of Toronto Inquiry that she was shocked and distraught to learn about the data manipulation, wished that she had detected the error at an earlier stage, and that she had no intention to deceive anyone. She also falsely asserted that the complaint against her was motivated by Dr. Cummings’ “deep personal interest” in ultimately proving nitrates can be used to prevent fractures.
Women’s College Hospital (“WCH”) Investigation
Following receipt of the University of Toronto Inquiry report, WCH assumed the sole jurisdiction for the investigation. On June 1, 2015, an Investigative Committee (the “IC”) was appointed with a mandate to investigate the allegations of research misconduct alleged in the complaint and to expand the investigation if the evidence disclosed new related instances of possible misconduct.
After conducting its extensive investigation, in a report dated October 8, 2015, the IC concluded that she engaged in numerous acts of research misconduct, including that Dr. Jamal fabricated study data in each of the NABT, Scerlostin and JAMA studies to support the study hypothesis. Dr. Jamal acknowledges the extensive steps the IC was required to take to uncover her data falsification. As part of the IC’s investigation, a forensic expert was retained to examine various computer hard- drives, email communication, data sets and documents, among other things, passed between researchers and collaborators in the JAMA Study, the Sclerostin Study and the NABT Study.
Dr. Jamal Engaged in Professional Misconduct: NABT Study
Following the extensive investigation of the IC, with respect to the NABT Study, it was determined, and Dr. Jamal admits, that:
-Dr. Jamal manipulated study data in August 2014 with the intention of supporting the underlying - hypothesis that nitrates reduced bone loss and prevent osteoporotic fracture;
-Dr. Jamal presented these falsified results to her collaborators and to a small audience at the ASBMR conference;
-Contrary to the repeated assertions made by Dr. Jamal prior to and during the investigation, her Research Associate had no role in the falsification of the study data. These allegations by Dr. Jamal were wholly unjustified and completely inappropriate; and,
-Dr. Jamal engaged in numerous acts to avoid detection and falsely implicate her Research Associate once Dr. Eastell raised concerns that the data had been systematically modified, including ensuring her Research Associate was not copied on various emails, sending falsified data sets to Dr. Eastell and representing those were the data sets prepared by her Research Associate, and misrepresenting to her Research Associate what she had sent Dr. Eastell. Dr. Jamal continued to do the same throughout the University of Toronto Inquiry.
Dr. Jamal Engaged in Professional Misconduct: Sclerostin Study
The IC also closely examined the Sclerostin Study which had been initiated in or around 2011 following the JAMA Study. The hypothesis of the Sclerostin Study was that active treatment subjects receiving nitroglycerin would experience a decrease in serum sclerostin and a corresponding increase in bone mass.
In December 2011, Dr. Jamal provided her collaborators with data in a form ready for statistical analysis, which she purported was the raw data for the Sclerostin Study. However, as revealed by the IC investigation, unbeknownst to her collaborators, the data contained in these files had been manipulated by Dr. Jamal in a systematic fashion to support the study hypothesis.
In early 2012, Dr. Jamal’s colleagues noted that Dr. Jamal appeared to have relied on a different set of data than one of their collaborators who had run his own statistical analysis. Dr. Jamal initially identified the correct data, but then, on more than one occasion, specifically directed her colleague to rely on the data she had falsified, claiming it was the correct data. The statistical analysis prepared by her colleague based on the falsified data demonstrated significant reduction of sclerostin in the treatment group. Ultimately, Dr. Jamal’s colleagues prepared a manuscript based on this analysis, stating “our results suggest that nitroglycerin treatment substantially increases bone mass in postmenopausal women by decreasing sclerostin production”. This conclusion was based on Dr. Jamal’s manipulated data. Dr. Jamal reviewed and approved the paper and is identified as an author. The manuscript was submitted for review but was rejected. It was not resubmitted.
With respect to the Sclerostin Study, the IC determined, and Dr. Jamal admits:
-Dr. Jamal manipulated study data with the intention of supporting the underlying hypothesis that active treatment subjects would see a decrease in serum sclerostin; and
-Dr. Jamal directed her colleague to rely on the altered data, representing that it was the accurate data when discrepancies arose in the analysis.
Dr. Jamal Engaged in Professional Misconduct: JAMA Study
Intentional manipulation of Study Data
The JAMA study commenced in November 2005 and was completed in March 2010. It involved obtaining three different measurements from study subjects: Bone Mineral Density (“BMD”) involving scans carried out on study subjects; Peripheral quantitative computed tomography (“pQCT”) involving scans carried out on study subjects; and BSAP and NTx measured using subjects’ serum and urine samples. Dr. Jamal had full access to all of the data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis.
The IC’s investigation revealed that Dr. Jamal:
-Systematically altered the BMD data intentionally manipulating it to increase the apparent effectiveness of the treatment, in support of the study hypothesis;
-Systematically altered the pQCT data intentionally manipulating it to increase the apparent effectiveness of the treatment, in support of the study hypothesis; and,
-Systematically altered BSAP and NTx data by reducing the placebo values and increasing the active treatment group data by constant amounts, in support of the study hypothesis.
Dr. Jamal’s data manipulation remained undetected until 2015 when concern arose in the NABT Study and her collaborators became frustrated with her failure to deliver the raw data for the JAMA Study, giving rise to the complaint and ultimately the IC’s investigation.
Deceiving Colleagues during IC Investigation
When Dr. Cummings and Dr. Eastell discussed the need to confirm the published JAMA results given the NABT results and asked Dr. Jamal to provide the raw data for the JAMA Study, Dr. Jamal sent to Dr. Cummings what she purported was the “raw data” for one of the study measurements. However, the data she provided was data that she had systematically modified. During the IC’s investigation, Dr. Jamal continued to falsely maintain that the data she had sent to Dr. Cummings in April 2015 was the actual raw data for the particular measurement.
The IC determined that some of the raw data for the JAMA study had been available to Dr. Jamal such that she could have provided this information to her collaborators as requested. Instead, Dr. Jamal provided altered patient records attempting to pass them off as “raw data” in her possession, and knowingly provided inaccurate data to her collaborators.
Tampering with Patient Records in an Attempt to Avoid Detection
The IC investigation revealed that active treatment subjects’ BMD scans had been replaced with scans from other patients, most of whom were not participants in the JAMA Study. Dr. Jamal took BMD scans (patient records) from various patients who had no connection to the study, redacted their names and other information, including scan dates, hand wrote a study subject ID on the patient record, and attempted to pass off the scans as the “raw data” that supported the published study analysis. To do this, Dr. Jamal accessed confidential patient records for an improper purpose, without consent or legal authority to do so, in violation of patient confidentiality and privacy. Dr. Jamal had provided photocopies of these doctored BMD scans to Dr. Cummings under the pretense of providing him the raw data for the JAMA Study.
The IC investigation also revealed that Dr. Jamal manually altered pQCT records (patient records), by superimposing false data onto the actual patient record. The alteration was deliberate and designed to give the appearance that the hard copy pQCT scans Dr. Jamal was providing to the IC was “raw data” that matched the published JAMA results. Dr. Jamal held out these doctored records to the IC as bona fide patient records containing what purported to be the “raw data” that supported the published study analysis.
Dr. Jamal’s actions with original patient records (BMD scans and pQCT records) amount to a misuse and misappropriation of confidential patient information, in violation of patient confidentiality and privacy.
Dr. Jamal’s misconduct during investigation
Dr. Jamal also engaged in additional misconduct during the IC’s investigation by taking steps to make relevant evidence unavailable to the IC:
-When advised that a forensic investigation was going to be conducted on some or all of her computers, she was untruthful regarding the whereabouts of her old computer she used up until January 2014, initially stating she was unaware of its whereabouts and then later acknowledging accessing it. Video footage and witness accounts established that Dr. Jamal removed a computer from the premises during the investigation and it could not be located. In addition Dr. Jamal removed her current computer from her office and brought it to her home. While she falsely claimed she did not alter any data on her current computer, forensic analysis established that she did, in fact, delete relevant files on May 23, 2015, thereby destroying evidence and obstructing the investigation.
-Dr. Jamal entered Canadian Blood Services where raw blood and urine samples from the JAMA Study were stored. She manipulated freezer temperatures, affecting the samples that had been maintained, in order to cover up her misconduct.
Some Consequences of Dr. Jamal’s Misconduct
As early as 2010, Dr. Jamal falsified results leading to the JAMA publication to support a clinical hypothesis, and further studies intended to bolster these findings (Sclerostin and NABT). As part of the JAMA Study, falsified results were communicated to study participants. In some cases, results were copied to the study participant’s family doctor; in other cases, study participants were told to take the results to their family doctor. None of the participants had osteoporosis. The consent forms executed by patients advised that if the study was successful, further research would be required before nitroglycerin treatment would be available for use.
Knowing that she had falsified the JAMA results to support her hypothesis regarding nitroglycerin treatment, Dr. Jamal then continued to collaborate with others, to obtain funding, including from NIH and CIHR, to conduct further research (for example, the Sclerostin Study and NABT Study), including research on human subjects, without any evidentiary foundation.
There are known risks associated with nitrate treatment, including headache, nausea and postural hypotension. In the JAMA Study, for example, 104 of 157 women who dropped out of the one-week run-in phase reported headaches and nausea. Dr. Jamal placed patients in a subsequent clinical study (the NABT Study), exposed these patients at a minimum to the risk of headaches, and did so with knowledge that there was no basis to support any potential benefit.
Following the IC Investigation, WCH notified each participant in the JAMA Study that they may have in fact received incorrect results. Participants were asked to advise their family physicians, who could in turn consider this information in the ongoing monitoring of the individual’s bone health. WCH has stated that “there is no evidence of negative outcomes for any of these research participants.”
In December 2015, the Journal of the American Medical Association retracted the JAMA Study.
On May 4, 2016, the President of CIHR declared Dr. Jamal permanently ineligible to hold, participate in, or apply for CIHR funding or funding from the other two federal research agencies (NSERC or SSHRC) or any Tri-Agency programs; and permanently ineligible to participate in Agency review processes. She is also required to reimburse CIHR for the funds spent on the study.
Disposition
On March 6, 2018, the Discipline Committee ordered and directed that:
-the Registrar revoke Dr. Jamal’s certificate of registration effective immediately.
- Dr. Jamal appear before the panel to be reprimanded.
- Dr. Jamal pay costs to the College in the amount of $5,500.00 within 30 days of the date of this Order.